RxPG News : Diabetes

Frequent napping associated with an increased prevalence of type 2 diabetes

Mon, 01 Mar 2010 13:24:24 PST

( from http://www.rxpgnews.com ) A study in the March 1 issue of the journal Sleep shows that frequent napping is associated with an elevated prevalence of type 2 diabetes and impaired fasting glucose in an older Chinese population.

Results show that the prevalence of type 2 diabetes was 36 percent higher (adjusted odds ratio = 1.36) in participants who reported napping four to six times a week and 28 percent higher (OR = 1.28) in those who napped daily. Similar associations were found between napping and impaired fasting glucose. The observed associations were unaltered in statistical analyses that removed participants with potential ill health and daytime sleepiness, suggesting it is less likely that diabetes leads to daytime sleepiness and raising the possibility that napping may increase the risk of diabetes.

According to the authors, napping in China is a social norm, which is practiced by all ages primarily as a habit started in childhood. In Western countries, napping is less common and is often unplanned and prompted by sleepiness likely caused by aging, deteriorating health status or nighttime complaints.

Lead author Neil Thomas, PhD, reader in epidemiology at the University of Birmingham, U.K., said that additional research is needed to determine if napping itself plays a causative role in the development of type 2 diabetes, or if other factors are involved.

"In many non-Mediterranean, Western countries a large proportion of those that nap are generally older or have other conditions that cause tiredness and create an urge to nap," said Thomas. "The napping can therefore be a marker of disease."

This cross-sectional study analyzed baseline data from the Guangzhou Biobank Cohort Study, a collaboration between the Guangzhou Number 12 People's Hospital and the Universities of Birmingham and Hong Kong. The community-based study took place in Guangzhou, China, where 19,567 participants between the ages of 50 and 93 years were recruited from 2003 to 2004 and 2005 to 2006. The sample comprised 13,972 women with a mean age of 61.4 years and 5,595 men with an average age of 64.2 years.

Participants underwent a half-day assessment, which included a structured interview on lifestyle and medical history, and a physical examination. Self-reported frequency of napping was obtained by questionnaire, and type 2 diabetes was assessed by a fasting blood glucose sample and/or self-reports of physician diagnosis or treatment. Participants were asked to describe their napping habits and daytime sleepiness.

Type 2 diabetes was identified in 13.5 percent of the sample and was more prevalent in people who reported napping daily (15.1 percent) and in those who napped four to six times per week (14.7 percent). Logistic regression models were constructed to assess the relationship between napping and diabetes and impaired fasting glucose, adjusting for demographics, lifestyle, sleep habits, health status, body fat and metabolic markers.

At least one nap per week was reported by 67.2 percent of participants, more commonly in males (76.4 percent) than in females (63.6 percent). About 59.4 percent of these people reported napping daily. Total sleep duration was longer and daytime sleepiness was reported less often in more frequent nappers than in people who never napped.

In a sub-sample of 3,822 participants who were re-contacted for additional information about sleep habits, there was a statistically significant trend of increasing risk of diabetes with longer nap duration. Compared with people who never took naps, the risk of diabetes was 41 percent higher (OR = 1.41) for people who took naps that lasted longer than 30 minutes and 35 percent higher (OR = 1.35) for people whose naps lasted 30 minutes or less.

The authors noted that the association between napping and diabetes was observed despite the fact that nappers had higher levels of physical activity, which has been shown to reduce the risk of diabetes. This suggests that the relationship between napping and diabetes might have been stronger had it not been offset by the protective effects of physical activity. The authors added that there will be profound public health implications in China if the relationship between napping and increased risk of type 2 diabetes is confirmed in longitudinal studies, as the nation is currently affected by an emerging diabetes epidemic.

Changes during menopause increases risk of heart disease and stroke

Tue, 23 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO- When women hear the word menopause, they often think about hot flashes, hormone shifts and mood swings. But what about heart disease? Studies show a woman's risk of heart disease intensifies drastically around the time of natural menopause, which for most women is around the age of 50. This news may come as a surprise, but experts explain that understanding risk factors is an important first step, and reassure women that there are ways to lower your risk.

Many women younger than 50 have not yet gone through menopause and still have high levels of the female hormone estrogen in their blood, which is thought to help protect the heart. After menopause, however, the levels of estrogen in a woman's body drop significantly and can contribute to the higher risks of cardiovascular disease, explains Vera Rigolin,MD, associate director of the Center for Women's Cardiovascular Health in the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital.

Weight gain is also a factor that may play a role in postmenopausal risk of heart disease. Maintaining a healthy weight often becomes difficult after your body experiences a change in hormone levels. Extra mass can take a toll on the body causing physical inactivity, high blood pressure, diabetes, and high cholesterol, all risk factors that can lead to heart attack and stroke.

Detecting heart disease in women can be difficult. Many women are unaware that symptoms of the disease may differ from those of men. Although women often experience chest discomfort when presenting with a heart attack, they commonly have other, more subtle symptoms, including fatigue, nausea, shortness of breath, jaw pain and general discomfort in the chest and abdominal area.

In some women, plaque can build in the smallest blood vessels called the microvascular circulation. These blockages do not show up in an angiogram, says Rigolin. In these cases, we often use Magnetic Resonance Imaging (MRI) with medication to visualize blood flow within the small blood vessels when other standard tests do not provide us answers.

Women, especially those who are menopausal can reduce the risk of heart disease by adopting a healthy lifestyle.

If you are a smoker, quit immediately and avoid second hand smoke. Eat a diet rich in fruits and vegetables and exercise at least three times per week to maintain a healthy body weight, says Rigolin.

Rigolin also recommends visiting your health care provider at least once per year to have your blood pressure, blood sugar and cholesterol levels checked.

First-generation artificial pancreas system used overnight can improve diabetes control

Sat, 06 Feb 2010 12:48:29 PST

( from http://www.rxpgnews.com ) In a landmark study in children and teenagers with type 1 diabetes, JDRF-funded researchers at the University of Cambridge showed that using a first-generation artificial pancreas system overnight can lower the risk of low blood sugar emergencies while sleeping, and at the same time improve diabetes control.

Results from the studies are published in the February 5, 2010 issue of The Lancet, available online at www.thelancet.com.

The trials tested the safety and effectiveness of a first-generation artificial pancreas system used overnight in a hospital setting with participants between 5 and 18 years of age with type 1 diabetes. The system combined commercially available blood glucose sensors and insulin pumps, controlled by a sophisticated computer program that determined insulin dosage based on blood glucose levels while the participants slept.

Maintaining recommended blood sugar levels overnight is a major issue for people with type 1 diabetes - and particularly for the families of children with diabetes - because of the possibility of blood glucose dropping dangerously low during sleep and going unnoticed, which can lead to seizures, coma, and in some cases be fatal.

Notably, the Cambridge study showed that the children and teenagers spent twice as much time during the night within targeted blood glucose levels when their diabetes was regulated with the artificial pancreas system than when they followed conventional "manual" therapy. And low blood sugars were minimized.

"These studies show that automated systems not only can help people manage diabetes by maintaining good control, they will also improve quality of life for the people with type 1 diabetes and their families by lowering the risk for hypoglycemia," said Roman Hovorka, Ph.D., from the Institute of Metabolic Science at the University of Cambridge, the principal investigator of the study and lead author of the paper. "These results suggest that closed-loop devices may be able to significantly lower the patient's risk of developing complications later in life by reducing or even overcoming the burden of hypoglycemia."

"Without a doubt, the biggest worry for parents of kids with type 1 diabetes is that their child will have a low blood sugar emergency during the night, when they're hard to identify," said Aaron Kowalski, Ph.D., Assistant Vice President of Metabolic Control at JDRF and Director of the JDRF Artificial Pancreas Project. "This study is proof of principle that diabetes in kids can be safely managed overnight with an artificial pancreas. We need to redouble our efforts to move the artificial pancreas from a concept in the clinic to a reality in the home of kids and adults with type 1."

The first phase of the Cambridge study compared the effectiveness of a simple artificial pancreas system used overnight with standard blood testing and insulin delivery using a pump. It showed that the time participants spent in target blood glucose levels (between 70 mg/dL and 140 mg/dL) improved from 39% to 52%. The second phase of the study evaluated the effects of a using the same artificial pancreas system overnight with the additional variable of the participants eating a particularly large meal, which can impact overnight blood glucose levels. The results were comparable to the first phase of the research. The third phase of the study evaluated the effects of moderately intense exercise, which can also impact blood sugar levels. Using the automated system in this setting showed the greatest improvement in blood sugar control, with the amount of time spent in the target range increasing from 48% to 78%.

"The pooled data from the closed loop studies showed that blood glucose levels were 61% in target, and even increased to 75% in target after midnight when closed-loop became fully effective," said Dr. Hovorka. "Based on these results, this study is a significant step towards an artificial pancreas."

The Cambridge studies were randomized, controlled trials involving 17 children and adolescents conducted at the Wellcome Trust Clinical Research Facility at Addenbrooke's Hospital in Cambridge, United Kingdom over the course of 54 nights. Twelve subjects were used for the first study; 6 subjects were used for the second, and 9 for the third. Some 33 nights were on a closed-loop artificial pancreas system, while 21 nights were controlled (on standard therapy). During the closed-loop studies, continuous glucose measurements were fed into a computer program every 15 minutes, which calculated the insulin infusion rate; the insulin pump was adjusted manually by a research nurse. During control nights, the subject's standard insulin pump settings were applied.

Type 1 diabetes is an autoimmune disease in which the immune system attacks and kills off the cells in the pancreas that produce insulin, a hormone that enables people to convert food into energy. It affects 3 million American children, adolescents, and adults.

To manage their disease, people with type 1 diabetes need to measure their blood sugar multiple times throughout the day (typically by pricking a finger for a drop of blood), and pump insulin or inject themselves multiple times daily to keep blood sugar levels within a healthy range. That daily routine continues for life, because insulin administration does not cure diabetes.

Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of the disease, such as blindness and kidney disease - but that the fear of low blood sugar emergencies often prevents many people from achieving tight control, and remains a constant concern for those who manage their diabetes well. The landmark Diabetes Control and Complications Trial (DCCT) showed that with intensive insulin therapy, excellent blood glucose control was obtained, but at the expense of a considerable increase in hypoglycemia.

About JDRF's Artificial Pancreas Project
This study is the latest development within JDRF's Artificial Pancreas Project, and stems from the progress made since 2006 in the JDRF-funded Artificial Pancreas Consortium, a group of university-based mathematicians, engineers, and diabetes experts that has developed the computer programs needed for an artificial pancreas, and established their scientific feasibility. These academic studies within the Artificial Pancreas Project are an excellent complement, and essential to JDRF's work with industry participants to develop first -generation systems.

JDRF announced the first major non-exclusive industry initiatives of the Artificial Pancreas Project last month, when it entered into a non-exclusive partnership with Animas, a Johnson & Johnson company, to develop a first-generation artificial pancreas system. JDRF also announced a non-exclusive partnership with BD (Becton, Dickinson and Company) aimed at developing novel insulin delivery products - a key component of developing safe and effective artificial pancreas systems.

The eventual, ultimate goal of the JDRF Artificial Pancreas Project is speeding the development of automated diabetes management systems. The goal of an artificial pancreas has also been embraced by the U.S. Food and Drug Administration, which along with JDRF and National Institutes of Health, brought together scientists, regulators, industry, and patients for scientific workshops n the subject in 2005 and 2008; the FDA has designated an artificial pancreas as one of its "critical path" initiatives.

An artificial pancreas would measure blood sugar through a continuous glucose monitor (CGM), which continuously reads the glucose levels through a hair-thin tube inserted just below the skin, typically on the stomach. The CGM would beam those readings to an insulin pump. In an advanced system, the pump would house a sophisticated computer program that would automatically calculate the necessary amount of insulin, based on the CGM's glucose readings, and deliver the right amount of insulin.

The development of an artificial pancreas system is an essential step towards an ultimate cure for type 1 diabetes - a "bridge to a cure."

UCSF diabetes, brain tumor stem cell grants to drive development of therapies

Thu, 29 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Two teams of UCSF scientists have received grants from the California Institute for Regenerative Medicine to advance their stem cell based strategies for treating diabetes and brain tumors. The intent of the grants is for teams to file new drug applications to the U.S. Food and Drug Administration within four years, driving potential therapies toward clinical trials.

The two grants, awarded to collaborative scientific teams, total $39.2 million.

The diabetes grant is co-led by investigator Jeffrey Bluestone, PhD, director of the UCSF Diabetes Center, in collaboration with Novocell, Inc. Other UCSF members of the team are Michael German, MD, PhD; Matthias Hebrok, PhD; and Qizhi Tang, PhD.

The brain tumor grant is led by Mitchel Berger, MD, chair of the UCSF Department of Neurosurgery, in collaboration with Ludwig Institute for Cancer Research and Burnham Institute for Medical Research. Other UCSF members of the team are C. David James, PhD; Tomoko Ozawa, MD, PhD; Russell Pieper, PhD; Mei-Yin Polley, PhD; Michael Prados, MD; and Elizabeth Read, MD.

The projects are among 14 disease team grants announced today (Oct. 28, 2009) by CIRM. The grants focus on conditions ranging from brain tumors and diabetes to HIV, heart damage and amyotrophic lateral sclerosis, among others. They are the first issued by CIRM with the explicit intent of driving the development of therapies for approval by FDA for testing in clinical trials.

The multidisciplinary collaborations are intended to hasten the clinical trial development process, avoiding mistakes sometimes discovered late in the game and ensuring that clinically relevant issues are considered early.

The diabetes team, lauded as a dream team by the CIRM working group reviewers, received $19,999,937 over four years. The goal is to encapsulate islet progenitor cells generated from human embryonic stem cells in a durable, retrievable device and implant them into patients. The cells, which differentiate into glucose responsive islet beta cells after transplantation in vivo, have proven to be a successful strategy in treating rodents with chemically-induced diabetes.

The critical early proof-of-concept milestones have been completed, says Bluestone. Now we need to perform the manufacturing and laboratory testing required to assure reliable production of a safe and effective product, thereby generating the data needed to seek Food and Drug Administration approval to test the therapy in humans.

This is a very exciting early pre-clinical step, but, as is always the case in science, there are likely to be unexpected hurdles as we move forward, he says.

If successful, a Phase 1 safety trial in Type 1 diabetic patients could begin in three-four years from the initiation of the project.

The brain tumor team, which received $19,162,435, was characterized by the CIRM leaders as pioneers and leaders in their respective fields. The team will refine their strategy of using adult and fetal neural stem cells, as well as mesenchymal stem cells, genetically engineered to contain a tumor-killing gene to home in on glioblastoma multiforme, the most common and aggressive form of brain tumor. The studies in rodents engineered to develop human brain tumors were successful.

The strategy is based on the team's discovery that neural stem cells naturally seek out brain tumor cells and other types of disease cells. If successful, this approach would be an important advance in treating brain tumors of all kinds, says Berger. Current approaches -- surgery, radiation, pharmacological drugs and gene therapies -- are unable to reach widely disseminated tumor cells that become dispersed within normal brain structures.

If the strategy is approved by the FDA, it would be tested first in patients with recurring glioblastoma multiforme.

Obesity expert named Life Scientist of the Year

Wed, 28 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) A Monash University physiologist, whose research into weight management, obesity and diabetes has led to significant medical breakthroughs and drug design, has been awarded one of the nation's top research honours.

Michael Cowley received the prestigious Commonwealth Science Minister's Prize for Life Scientist of the Year.

Professor Cowley was last night presented with the award by the Minister for Innovation, Industry, Science and Industry Senator Kim Carr at Parliament House in Canberra.

The prize is granted to an internationally-renowned scientist who has completed their PhD within the last 10 years, and whose research has the potential to advance human welfare or society. He received $50,000, a silver medallion and a lapel pin.

I am tremendously grateful to receive this award, Professor Cowley said.

It's wonderful to know that my team and I are being recognised for the therapies we are developing for obesity.

Professor Cowley from the Department of Physiology has shown that neural circuits in the brain sense blood glucose and fat levels in the body. However a broken internal regulator can impair appetite regulation and lead to obesity, increasing the risk of Type 2 diabetes.

Professor Cowley has gone on to develop a combination anti-obesity drug called Contrave that can reactivate the fat sensor in obese patients and help them lose weight. In a large clinical trial in the US, participants who took Contrave lost between five and 10 per cent of their body weight in one year, with minimal to moderate side effects. Contrave combines new formulations of two existing drugs: Bupropion, an antidepressant; and Naltrexone, an addiction medication.

If the Food and Drug Administration approves the drug for prescription use in the US, Contrave could, subject to regulatory approval, be licensed in Australia.

Senior Deputy Vice-Chancellor and Deputy Vice-Chancellor (Research) Professor Edwina Cornish, who nominated Professor Cowley for the prize, said she was delighted with his success.

Michael's discoveries have the potential to radically change how we treat metabolic disease, and help Australia deal with a recognised crisis in Indigenous and non-Indigenous health, Professor Cornish said.

Professor Cowley's award caps off a successful year. He has received a Pfizer Australia Senior Research fellowship, Austin Doyle Lectureship, and Victorian Endowment for Science, Knowledge and Innovation Fellowship. Professor Cowley is also the inventor of 85 patents; co-founder and former Chief Scientific Officer of US-based biotechnology company, Orexigen Therapeutics; and has published 40 papers in peer-reviewed journals. His research has been profiled in the national and international media.

ERC Starting Grant for the researcher of kidney diseases

Fri, 11 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The European Research Council (ERC) expects to fund some 240 top researchers in its second prestigious ERC Starting Grant competition. This new wave of grantees follows the 299 researchers who received grants in the first Starting Grant competition in 2007.

In total, 2503 proposals were submitted to the second Starting Grant call.

Sanna Lehtonen's research group is studying the kidney glomerular ultrafiltration in both health and under pathological conditions, concentrating especially on studying the development of albuminuria that is an indicator of kidney disease. Specifically, we are interested in the pathophysiological mechanisms leading to the development of diabetic nephropathy, a serious complication of diabetes, Lehtonen says.

Up to one third of diabetic patients develop nephropathy. Microalbuminuria is the earliest sign of the complication, which may ultimately develop into end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance has been associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been found to be insulin responsive and to increase their glucose uptake upon insulin stimulation. It has also been shown that intact filamentous actin cytoskeleton is required for the insulin response. Our studies concentrate on analyzing the role of insulin signaling and glucose transport and the regulation of actin cytoskeleton in podocytes thereby aiming to define the mechanisms leading to perturbations in the kidney ultrafiltration function and development of albuminuria, Lehtonen tells.

The aim of Lehtonen's ERC project called DiaDrug is to clarify the mechanisms leading to the development of insulin resistance in podocytes and to study the association between insulin resistance and the development of albuminuria. The researchers will develop transgenic zebrafish and mouse models to study the role of proteins associated with insulin signaling in podocytes, both under normal and pathologic conditions.

Further, we aim to identify novel drug leads to treat insulin resistance by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of nephropathy in diabetic patients, Lehtonen says.

Sanna Lehtonen started her studies on kidney already during the early 1990's as a PhD student. Her thesis project was on developmental biology, and in particular, about identifying and characterizing novel genes associated with epithelial cell differentiation in the kidney. Later her studies have turned more in the direction of kidney diseases and most recently concentrated on analyzing the development of albuminuria during the development of diabetic nephropathy.

Diabetes is increasing at an alarming rate worldwide. Renal complication is the most serious of its complications and is also associated with an increased risk of cardiovascular disease. Treating diabetes consumes a large bulk of the healthcare costs in all countries, and therefore understanding the mechanisms leading to the development of the complications, especially nephropathy, identifying it at an earlier stage and finding novel drug targets and drugs to prevent the progression of the complication are currently under intensive research, Lehtonen states.

Receiving the ERC grant was really fantastic news for me. Now we can finally do some things that we were earlier able to only think and dream about, Lehtonen says.

DNA mutations linked to diabetes

Thu, 03 Sep 2009 03:59:12 PST

( from http://www.rxpgnews.com ) Genes that regulate the energy consumption of cells have a different structure and expression in type II diabetics than they do in healthy people, according to a new study from the Swedish medical university Karolinska Institutet published in Cell Metabolism. The researchers believe that these 'epigenetic mutations' might have a key part to play in the development of the disease.

Type II diabetes is characterised by a lower sensitivity to insulin in muscles and organs, and a reduced ability to consume energy in the form of glucose. Heredity and environmental factors (e.g. exercise) are both involved in the disease pathogenesis, but scientists are still unclear as to the mechanisms behind it.

A research group at Karolinska Institutet has now shown that genes in the muscle cells of diabetics are chemically modified through what is known as DNA methylation. They found that in muscles cells taken from patients with early-onset diabetes, a gene designated as PGC-1α was modified and had reduced expression. PGC-1α controls other genes that regulate the metabolism of glucose by the cell.

The team has also demonstrated that DNA methylation occurs rapidly, when cells from healthy people are exposed to certain factors associated with diabetes, such as raised levels of free fatty acids and cytokines. DNA methylation is a form of epigenetic regulation, a process involving chemical modifications that are imposed externally on genes and that alter their activity without any change to the underlying DNA sequence.

"This type of epigenetic modification might be the link that explains how environmental factors have a long-term influence on the development of type II diabetes," says Juleen Zierath, who led the study. "It remains to be seen whether the DNA methylation of this gene can be affected by, say, dietary factors."

Scarring key to link between obesity and diabetes

Thu, 13 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The team, in collaboration with University Hospital Aintree, the University of Warwick and researchers in Sweden, found that people classified as obese and those with pre-diabetes have raised levels of a protein called SPARC, that can cause tissue scarring. The research revealed that an increase in insulin, a hormone that controls blood sugar levels, and leptin, a hormone that regulates appetite, can trigger an increase in SPARC, which can prevent the proper storage of fat in fat tissue cells.

It is thought that leptin, in an attempt to balance energy levels in the body, could trigger SPARC to limit the storage of fat. SPARC can do this by increasing the formation of scars in fat tissue, which can prevent fat being stored safely in the body. Researchers found that this process could predispose obese patients to type 2 diabetes.

Professor John Wilding, from the University's School of Clinical Science, explains: We tested fat tissue of patients at University Hospital Aintree and found that an increase in leptin also increases SPARC levels, which reduces the safe storage of fat through the development of abnormal tissue scarring. Scarring of fat tissue is known to increase as we gain weight and we found that this is exacerbated by leptin, as well as an increase in insulin, produced by the pancreas.

Dr Katarina Kos, lead author of the research, added: Leptin is produced in fat cells to regulate appetite, but the body becomes resistant to the effects of appetite reduction in obese patients. Leptin continues to increase in response to overall fat mass and promotes scarring through increased SPARC levels. Once scarring occurs, the excess nutritional energy from fat cannot be taken up by fat cells and so remains in the blood and begins to gather around organs. As a result, fat cells of people classified as obese, may not fulfil their natural purpose to store fat.

Diabetes is caused by the cells' inability to respond to insulin, which would normally enable uptake of sugar from the blood. To compensate, the pancreas creates more insulin to clear blood sugar from the circulation. The pancreas becomes exhausted and is unable to produce sufficient insulin to keep up with the demands of the body. This results in the development of type 2 diabetes, which can cause problems such as lack of energy to the cells and, over time, damage to the eyes, kidneys and heart.

The research team, working with the Swedish fast food study group at Linkoping University, also found that weight gain, induced by more than doubling calorie intake through eating 'junk food', causes SPARC levels to increase by 33%. In a further study with the University of Gothenburg, scientists found that a reduced calorie diet can decrease SPARC levels and the stimulus for tissue scarring.

Researchers are now investigating why some people are more prone to fat tissue scarring than others and how further understanding of SPARC could contribute to future treatments for diabetes.

New powder can heal diabetic foot sores

Mon, 03 Aug 2009 16:11:32 PST

( from http://www.rxpgnews.com ) Foot complications, such as open wounds, can be difficult to treat or heal. However, a study has revealed that a new dressing powder, which acts exactly like a layer of skin, is cutting down healing time and reducing the quantum of pain ensuing from serious foot ulcers.

'This new powder comes together, in an amazing flexible film that mimics the wound's surface and helps it to retain moisture and protect the wound, but still allows the right amount of air flow needed for the wound to close,' said study co-author Tracey Vlahovic, Temple University School of Podiatric Medicine.

This wound powder is especially promising for the nearly 24 million Americans diagnosed with diabetes, where diabetic foot ulcers are the leading cause of non-traumatic, lower-limb amputations.

This powder's successful treatment of difficult foot wounds could potentially lead to a reduction in amputation rates.

In a recent American Podiatric Medical Association survey, 18 percent with diabetes reported that they had experienced a foot sore that would not heal.

This includes open sores on the feet as a result of inflammatory bowel disease, diabetes or skin cancer.

The study focused on atypical wounds with irregular shapes and causes. The wounds were treated with the powder dressing once a week for four to eight weeks.

The study ultimately showed that the powder dressing provided a painless, efficient, and protective treatment that assisted in closing the wound.

The powder also helped in preparing the wound for further interventions that are sometimes needed, including options like skin grafts.

These results were presented at the APMA's 97th Annual Scientific Meeting in Toronto July 30-Aug 2.

Lap-band weight-loss surgery can reverse metabolic syndrome in obese teens

Wed, 01 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) NEW YORK (June 30, 2009) -- A new study of obese adolescents has shown that laparoscopic gastric banding surgery -- the Lap-Band procedure -- not only helps them achieve significant weight loss but can also improve and even reverse metabolic syndrome, reducing their risk for cardiovascular disease and diabetes.

Metabolic syndrome is defined as a cluster of risk factors -- high blood pressure; low levels of HDL or good cholesterol; excessive abdominal fat; and elevated levels of blood sugar, C-reactive protein and triglycerides -- that increase a person's chances of developing cardiovascular disease or diabetes later in life. The single biggest risk factor is obesity, and metabolic syndrome usually improves when a person loses weight.

The study was led by Drs. Ilene Fennoy, Jeffrey Zitsman and colleagues at NewYork-Presbyterian Morgan Stanley Children's Hospital and Columbia University Medical Center and presented at the annual Endocrine Society meeting in Washington, D.C.

An estimated 17 percent of all American adolescents are obese, and increasing numbers of them also have metabolic syndrome, says Dr. Fennoy, a pediatric endocrinologist at NewYork-Presbyterian Morgan Stanley Children's Hospital, clinical professor of pediatrics at the Columbia University College of Physicians and Surgeons and co-author of the study. Until recently, there have been few treatments capable of helping these young patients lose weight, much less improving their lifelong health prospects. The Lap-Band may well be a useful intervention for tackling teen obesity -- which is why it is so important to investigate the procedure's safety and efficacy in this growing population.

In the new study, Dr. Fennoy and her colleagues followed 24 morbidly obese adolescents between the ages of 14 and 17 who underwent the Lap-Band procedure. The study participants either had a BMI of greater than 40 or greater than 35 if already suffering from diabetes or obesity-related illnesses.

Six months after surgery, they noted a significant drop in participants' BMI, waist circumference, and blood levels of C-reactive protein. These indicators continued to improve among the 12 patients being followed up at the one-year point.

Other measures of metabolic syndrome such as blood lipid and sugar levels, the authors reported, came down quickly in the first six months, with less dramatic changes seen one year after surgery.

Of all the bariatric procedures, she says, the Lap-Band is the most benign, with complication rates of less than 1 percent. The device, inserted via minimally invasive laparoscopic surgery, consists of a simple band to make the stomach smaller and a balloon that can be decompressed when necessary, she explains.

Although it is technically reversible, the procedure should be considered a long-term solution for extreme and intractable obesity.

The Lap-Band is the favored bariatric procedure in Europe, while in the U.S., gastric bypass has been the preferred approach. At present, NewYork-Presbyterian Morgan Stanley Children's Hospital/Columbia University Medical Center is one of a few medical centers offering the Lap-Band option in this country.

The Lap-Band procedure, an approved treatment for adults with extreme obesity, has not yet been thoroughly studied in adolescents. Larger, multicenter studies with longer follow-up periods will be needed, Dr. Fennoy says, to validate the findings of the current study.

Polycystic ovarian syndrome: New light on its causes and its effect on brothers

Tue, 30 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, The Netherlands: Researchers have found evidence that chronic disease in either a mother or father can create unfavourable conditions in the womb that are associated with the development of polycystic ovarian syndrome (PCOS) in daughters. In another study, researchers found that brothers of women with PCOS and insulin resistance are themselves at greater risk of developing insulin resistance or diabetes, suggesting that factors associated with the condition can be passed down to sons as well as daughters.

The two studies were presented to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam heard today (Tuesday).

Associate Professor Michael Davies told a news briefing: We already know from clinical studies of women with reproductive problems that foetal growth restriction is associated with the development of PCOS symptoms in daughters, and that problems during pregnancy and in the way the mother adapts to the metabolic challenge of pregnancy can indicate the future cardiovascular health of both the mother and the child. What we don't know is whether giving birth to a daughter who later develops PCOS is associated with increased, long term cardiovascular disease risk in the mother. Nor do we know whether conditions underlying chronic disease in the father increases the risk of PCOS in the daughter.

Prof Davies, co-director of the Research Centre for the Early Origins of Health and Disease at the University of Adelaide (Australia), looked at records for all female babies who were born and survived between 1973-1976 at The Queen Elizabeth Hospital in Adelaide. He and his colleagues interviewed the daughters to build up a picture of their health and any history of chronic disease in their parents. So far, 998 (63%) have responded, and Prof Davies reported preliminary data up to mid-1975 to the conference.

Sixty-two daughters (6.2% of the group) had a pre-existing diagnosis of PCOS. Mothers of these women tended to have elevated blood pressure during pregnancy. Daughters were nearly eight times as likely to have PCOS if their mothers had it, and they had a slightly higher risk if their mothers smoked during pregnancy. Mothers were 1.6 times as likely to have high blood pressure in later life if their daughters developed PCOS. If their fathers had heart disease or stroke, the daughters also had a higher risk of PCOS: double and three times the risk respectively. A history of diabetes in either parent was not significant.

Prof Davies said: These findings suggest a new pathway for the development of PCOS. We think that factors associated with the pre-existence of cardiovascular dysfunction in the mother or the father, and which operate during pregnancy, may create adverse conditions for the foetus, which alter the metabolic profile of offspring, leading to insulin resistance and reproductive consequences, such as PCOS, for daughters. A family history of diabetes is, therefore, not essential to observe an insulin resistance-related disease in offspring.

He said it was still unclear exactly how the cardiovascular risk in the father affected the daughter. We firstly need to consider the potential role of a common environment; for instance, that families with high levels of obesity (and therefore cardiovascular disease) will also tend to have heavy daughters who are thereby more likely to be affected by PCOS. However, the paternal effect that we saw was independent of the daughter's weight, maternal age, socioeconomic status, maternal smoking, and country of birth, which suggests either a direct genetic effect on the daughter, or an effect of paternal genetic factors that are expressed during pregnancy.

Dr Verena Mattle told the news briefing that her study was the first to show that brothers of women who had PCOS and insulin resistance were themselves more likely to develop insulin resistance or even diabetes or dyslipidaemia (a disruption in the levels of lipids (or fats) in the blood).

Until now, it was not clear whether the male relatives of women with PCOS were at increased risk for the metabolic disorders associated with PCOS, said Dr Mattle, who is chief resident at the University Clinic of Gynecological Endocrinology and Reproduction Medicine in Innsbruck (Austria).

Dr Mattle and her colleagues conducted oral glucose tolerance tests on 15 brothers of sisters with PCOS and insulin resistance (group 1). They also performed a serum analysis to determine lipid levels. As a control, nine brothers of sisters with PCOS but without insulin resistance were included in the study (group 2).

The researchers found that in the first group eight brothers showed an insulin resistance, one was diagnosed with diabetes and six had a normal glucose tolerance test. All nine affected brothers had a body mass index (BMI) between 19-31 kg/m2 and had elevated cholesterol and triglyceride levels. The six unaffected brothers had a BMI between 23-29, and none had high levels of cholesterol or triglycerides. In the second group, no insulin resistance was diagnosed. BMI was between 18-27 and two brothers had elevated cholesterol levels. Although there was a trend towards higher BMI in the first group, Dr Mattle said there was no statistically significant difference in BMIs between the two groups.

Dr Mattle said: These results mean that we should pay attention to the health not only of women with PCOS but also to their brothers as they seem to have an increased risk for the medical problems that make up the metabolic syndrome, such as insulin resistance, diabetes and cardiovascular disease. Our findings are also in accordance with the hypothesis that not only is PCOS is a heritable disease, but that factors associated with it, such as insulin resistance, can be passed down to the next generation of either sex.

She said that it could not be the case that the high BMI by itself could have caused the insulin resistance and diabetes in the affected brothers. There must be a correlation between PCOS and insulin resistance because we could only find brothers with insulin resistance in the group that had sisters with PCOS and insulin resistance, but we couldn't find brothers with insulin resistance in the group that had sisters with PCOS and no insulin resistance. It is known that about 50% of women with PCOS are insulin resistant and also that lean PCOS patients are insulin resistant. The BMI of insulin-resistant and non-resistant brothers were not statistically different.

Dr Mattle and her colleagues are continuing to test brothers of women with PCOS for insulin resistance and lipid levels to collect more data from a larger group. At this stage we would hesitate to say that a genetic inheritance is definitely playing a role in the increased risk of insulin resistance and other, related conditions in these brothers. We need to explore the possible effect of conditions in the womb and also the role of the environment. However, we think our data strongly support the view that brothers of women with PCOS and insulin resistance may have an increased risk of insulin resistance, diabetes and other, adverse metabolic conditions, she concluded

Snoring pregnant women at higher risk for gestational diabetes

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) CHICAGO --- If you are pregnant and your mate complains your frequent snoring is rattling the bedroom windows, you may have bigger problems than an annoyed, sleep-deprived partner.

A new study from researchers at the Northwestern University Feinberg School of Medicine has found that women who reported frequent snoring during their pregnancy were more likely to develop gestational diabetes -- a condition than can cause health problems for the mother and baby. The study also found pregnancy increases the likelihood that a woman will snore.

This is the first study to report a link between snoring and gestational diabetes.

For the study, 189 healthy women completed a sleep survey at the time of enrollment (six to 20 weeks gestation) and in the third trimester.

Pregnant women who were frequent snorers had a 14.3 percent chance of developing gestational diabetes, while women who did not snore had a 3.3 percent chance. Even when researchers controlled for other factors that could contribute to gestational diabetes such as body mass index, age, race and ethnicity, frequent snoring was still associated with the disease.

Principal investigator Francesca Facco, M.D., a fellow at Northwestern's Feinberg School, will present her findings at the SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies June 11.

Sleep disturbances during pregnancy may negatively affect your cardiovascular system or metabolism, said Facco, who in August will become an assistant professor of obstetrics and gynecology at the Feinberg School and a maternal and fetal medicine physician at Northwestern Memorial Hospital.

Snoring may be a sign of poor air flow and diminished oxygenation during sleep that can cause a cascade of events in your body, Facco said. This may activate your sympathetic nervous system, so your blood pressure rises at night. This can also provoke inflammatory and metabolic changes, increasing the risk of diabetes or poor sugar tolerance.

The study also showed more women became frequent snorers as their pregnancies progressed. Early in pregnancy, 11 percent of women in the study reported frequent snoring; by the third trimester, the number rose to 16.5 percent. Frequent snoring was defined as snoring three or more nights a week.

Facco said snoring during pregnancy may be triggered by weight gain and edema (a buildup of fluid), which can increase airway resistance. Exactly how the snoring is linked to gestational diabetes is not yet known.

About 4 percent of pregnant women develop gestational diabetes, a condition in which women without previously diagnosed diabetes develop high blood sugar levels during pregnancy. Babies born to mothers with gestational diabetes are at increased risk of problems such as being large for gestational age, which may lead to delivery complications. These babies may also have low blood sugar levels and are at increased risk of becoming obese or developing impaired sugar tolerance or metabolic syndrome later in life.

While gestational diabetes usually resolves after pregnancy, women who develop it are at higher risk for type 2 diabetes later in life.

Facco said further studies are needed to understand the association between snoring and gestational diabetes and to develop interventions to treat sleep disorders during pregnancy.

If snoring is bothering a woman who is pregnant, she should seek a consultation with a sleep specialist, Facco said.

In related study, also to be presented at the SLEEP 2009 meeting, Facco found sleep disturbances such as restless legs syndrome and insomnia increase significantly during pregnancy.

Nicotine induces prediabetes, likely contributes to high prevalence of heart disease in smokers

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers have discovered a reason why smoking greatly increases the risk of heart disease and stroke. Nicotine promotes insulin resistance, also called prediabetes, which is a risk factor for cardiovascular disease, according to the new study, which was presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Additionally, the study authors were able to partially reverse this harmful effect of nicotine in mice by treating them with the nicotine antagonist mecamylamine, a drug that blunts the action of nicotine.

The study, which the National Institutes of Health funded, was conducted by researchers at Charles Drew University of Medicine and Science in Los Angeles and Western University of Health Sciences in Pomona, Calif.

Their results may explain why cigarette smokers have a high cardiovascular death rate, even though smoking causes weight loss, which should protect against heart disease, said the study's lead author, Theodore Friedman, MD, PhD, chief of the endocrinology division at Charles Drew University.

Prediabetes and diabetes are known risk factors for cardiovascular disease. Past studies show that cigarette smokers tend to be insulin resistant, meaning that their hormone insulin does not work properly. To compensate, their blood glucose (sugar) levels become higher than normal but not yet high enough for diabetes. Smokers also have higher rates of diabetes, but it is not clear whether smoking is the cause, because they could have other risk factors, Friedman explained.

Some studies demonstrate that nicotine and cigarette smoking induce high levels of the stress hormone cortisol. As cortisol excess is known to induce insulin resistance, it has been suggested that glucocorticoids, such as cortisol, are the missing [causative] link between cigarette smoking and insulin resistance, Friedman said.

The new study results suggest this theory is correct, he said. The researchers studied the effects, on 24 adult mice, of twice-daily injections of nicotine for 2 weeks. The mice ate less food than control mice that received injections without nicotine, and they also lost weight and had less fat. Despite this, the mice receiving nicotine developed prediabetes (insulin resistance), which subsequent mecamylamine treatment improved somewhat. These mice also had high cortisol levels in their blood and tissues, and mecamylamine blocked this effect.

Our results suggest that reducing tissue glucocorticoid levels or decreasing insulin resistance may reduce the heart disease seen in smokers, Friedman said. We anticipate that in the future there will be drugs to specifically block the effect of nicotine on glucocorticoids and insulin resistance.

Currently available nicotine antagonists are not specific enough to completely block nicotine's effects or they have bothersome side effects, so better drugs are needed for this purpose, he said.

Gene triggers for diabetes found

Wed, 13 May 2009 14:54:33 PST

( from http://www.rxpgnews.com ) Sydney, May 12 - An international team of scientists has identified more than 40 genes, including 25 new ones, that could be factors in triggering type-1 diabetes.

Leading the Asia Pacific arm of the research group, Grant Morahan, professor, Western Australian Institute for Medical Research -, described this as one of the largest ever genetic studies into type-1 diabetes and among 'the most significant discoveries'.

'Where this discovery has much potential is that it could show us how to stop the disease returning by controlling how the risk genes work,' he said.

'This study involved screening DNA samples donated by more than 10,000 people with type-1 diabetes from across the world, and more than 11,000 people without the condition - including more than 2,000 families in which two children have type-1 diabetes.

'What's really surprising about these findings is not only did we find so many new genes, but we've also come across risk factors that are located between genes along the chromosomes, and at least three of these are in what we call 'gene deserts.'

'The purpose of gene deserts is still a scientific mystery, so this discovery could give us an insight into the function of these chromosome regions, as well as clues to how type-1 diabetes develops.'

The international study was funded by United State's National Institutes of Health -, said a WAIMR release.

The research was published in Nature Genetics online on Monday and will feature in the June edition of the journal.

Increased food intake alone explains the increase in body weight in the United States

Fri, 08 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: New research that uses an innovative approach to study, for the first time, the relative contributions of food and exercise habits to the development of the obesity epidemic has concluded that the rise in obesity in the United States since the 1970s was virtually all due to increased energy intake.

How much of the obesity epidemic has been caused by excess calorie intake and how much by reductions in physical activity has been long debated and while experts agree that making it easier for people to eat less and exercise more are both important for combating it, they debate where the public health focus should be.

A study presented on Friday at the European Congress on Obesity is the first to examine the question of the proportional contributions to the obesity epidemic by combining metabolic relationships, the laws of thermodynamics, epidemiological data and agricultural data.

There have been a lot of assumptions that both reduced physical activity and increased energy intake have been major drivers of the obesity epidemic. Until now, nobody has proposed how to quantify their relative contributions to the rise in obesity since the 1970s. This study demonstrates that the weight gain in the American population seems to be virtually all explained by eating more calories. It appears that changes in physical activity played a minimal role, said the study's leader, Professor Boyd Swinburn, chair of population health and director of the World Health Organization Collaborating Centre for Obesity Prevention at Deakin University in Australia.

The scientists started by testing 1,399 adults and 963 children to determine how many calories their bodies burn in total under free-living conditions. The test is the most accurate measure of total calorie burning in real-life situations.

Once they had determined each person's calorie burning rate, Swinburn and his colleagues were able to calculate how much adults needed to eat in order to maintain a stable weight and how much children needed to eat in order to maintain a normal growth curve.

They then worked out how much Americans were actually eating, using national food supply data (the amount of food produced and imported, minus the amount exported, thrown away and used for animals or other non-human uses) from the 1970s and the early 2000s.

The researchers used their findings to predict how much weight they would expect Americans to have gained over the 30-year period studied if food intake were the only influence. They used data from a nationally representative survey (NHANES) that recorded the weight of Americans in the 1970s and early 2000s to determine the actual weight gain over that period.

If the actual weight increase was the same as what we predicted, that meant that food intake was virtually entirely responsible. If it wasn't, that meant changes in physical activity also played a role, Swinburn said. If the actual weight gain was higher than predicted, that would suggest that a decrease in physical activity played a role.

The researchers found that in children, the predicted and actual weight increase matched exactly, indicating that the increases in energy intake alone over the 30 years studied could explain the weight increase.

For adults, we predicted that they would be 10.8 kg heavier, but in fact they were 8.6 kg heavier. That suggests that excess food intake still explains the weight gain, but that there may have been increases in physical activity over the 30 years that have blunted what would otherwise have been a higher weight gain, Swinburn said.

To return to the average weights of the 1970s, we would need to reverse the increased food intake of about 350 calories a day for children (about one can of fizzy drink and a small portion of French fries) and 500 calories a day for adults (about one large hamburger), Swinburn said. Alternatively, we could achieve similar results by increasing physical activity by about 150 minutes a day of extra walking for children and 110 minutes for adults, but realistically, although a combination of both is needed, the focus would have to be on reducing calorie intake.

He emphasized that physical activity should not be ignored as a contributor to reducing obesity and should continue to be promoted because of its many other benefits, but that expectations regarding what can be achieved with exercise need to be lowered and public health policy shifted more toward encouraging people to eat less.

Study: Vibration plate machines may aid weight loss and trim abdominal fat

Fri, 08 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Amsterdam, the Netherlands: New research suggests that, if used properly, vibration plate exercise machines may help you lose weight and trim the particularly harmful belly fat between the organs.

In a study presented on Friday at the European Congress on Obesity, scientists found that overweight or obese people who regularly used the equipment in combination with a calorie restricted diet were more successful at long-term weight loss and shedding the fat around their abdominal organs than those who combined dieting with a more conventional fitness routine.

These machines are increasingly found in gyms across the industrialized world and have gathered a devoted following in some places, but there has not been any evidence that they help people lose weight. Our study, the first to investigate the effects of vibration in obese people, indicates it's a promising approach. It looks like these machines could be a useful addition to a weight control package, said the study's leader, Dirk Vissers, a physiotherapist at the Artesis University College and the University of Antwerp in Belgium.

Vissers and his colleagues studied the effects of the Power Plate in 61 overweight or obese people - mostly women - for a year. The intervention lasted six months, after which the scientists advised all the volunteers to do the best they could with a healthy diet and exercise regime on their own for another six months. Body measurements, including CT scans of abdominal fat, were taken at the beginning of the study and after three, six and 12 months.

The researchers divided the volunteers into four groups. One group was prescribed an individually calculated calorie restricted diet. Dietician visits were scheduled every fortnight for the first three months and every month for the second three months. The dieters were asked not to engage in any exercise for the duration of the six-month intervention.

A second group received the same diet intervention, with the addition of a conventional fitness regime. They attended supervised exercise classes twice a week for an hour and were urged to exercise on their own a third time each week. The sessions included group cycling, swimming, running, step aerobics and some general muscle strengthening exercises.

A third group got the diet intervention plus supervised vibration plate training instead of conventional exercise. They were asked not to do any aerobic exercise during the six-month intervention phase. The physiotherapists gradually increased the speed and intensity of the machine each week, as well as the variety and duration of the exercises from 30 seconds for each of 10 exercises to 60 seconds for each of 22 exercises, such as squats, lunges, calf raises, push-ups and abdominal crunches. The average time spent on the machine was 11.9 minutes per session in the first three months and 14.2 minutes in the second three months.

A fourth group got no intervention. There were no significant differences between the groups in obesity and abdominal, or visceral, fat at the start of the study.

Over the year, only the conventional fitness and vibration groups managed to maintain a 5% weight loss, which is what is considered enough to improve health, Vissers said.

During the first six months, the diet only group lost about 6% of their initial body weight, but could not maintain a 5% weight loss in the subsequent six months. The group that got diet plus conventional fitness lost about 7% of their initial body weight in the first six months, but they didn't put much of it back on and by the end of the study, they had managed to keep off a 6.9% loss. The vibration group lost 11% of their body weight during the intervention phase and by the end of the follow-up period they had maintained a 10.5% loss. The control group gained about 1.5% of their original body weight.

The vibration group lost 47.8 square centimetres of visceral fat during the first six months and still had a loss of 47.7 square centimetres at 12 months. Visceral fat shrank by 17.6 square centimetres in the conventional fitness group in the first six months, but by the end of the year, it was only 1.6 square centimetres less than at the beginning. The diet group had a visceral fat loss of 24.3 square centimetres after six months and 7.5 square centimetres after a year.

These are very encouraging results, but it doesn't mean people trying to lose weight can ditch aerobic exercise and jump on the vibration plate instead. They still need a healthy diet and aerobic exercise, but this could be a viable alternative to weight lifting, Vissers said, explaining that the plate works by making muscles rapidly contract, which builds lean muscle mass.

People say vibration machines are fitness for lazy people. It may feel like a short cut, but if it's easy, you are not doing it properly, he added. Supervision in the beginning is imperative and the longer the better. What we see in gyms very often - people just standing on the machine holding the handles - is not going to do anything.

Vissers said further research on a larger group of obese patients is needed to confirm how beneficial the machines are. His team is also planning to study why vibration seems to be more effective than aerobic exercise in trimming visceral fat, including whether increased blood flow to the abdomen and hormonal response to vibration might play a role in more efficient fat breakdown. His study was funded by the Artesis University College of Antwerp.

Gene therapy appears safe to regenerate gum tissue

Tue, 07 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Scientists at the University of Michigan have developed a method of gene delivery that appears safe for regenerating tooth-supporting gum tissue---a discovery that assuages one of the biggest safety concerns surrounding gene therapy research and tissue engineering.

Gene therapy is an accepted, viable therapeutic concept, but safety is a major hurdle, said William Giannobile, professor at the U-M School of Dentistry. The most notable incident highlighting the safety concerns of gene therapy research and treatment occurred several years ago when a teenager died when given the adenovirus during a gene therapy clinical trial at the University of Pennsylvania.

The U-M therapy also uses the adenovirus, Giannobile said, but the big difference in the U-M approach lies in the local application and much lower dose. Instead of injecting the genes into the blood vessels, where they can then travel through the bloodstream and result in unexpected and sometimes fatal reactions, U-M scientists put the genes on a localized area, directly on the tissue during surgery much like a paste.

What the U-M study showed is (the topical method) is very well contained and doesn't distribute throughout the body, said Giannobile, who also directs the Michigan Center for Oral Health Research and has an appointment at the U-M College of Engineering's Department of Biomedical Engineering. This approach alleviates the safety concern about negative reactions within the body.

When the teenager died, it got into his bloodstream and he reacted to it. It was tragic. This is the first study of periodontal disease therapy that demonstrates the distribution of these genes is very safe, suggesting that it could be used in the clinic for clinical application.

Our study doesn't look at all the safety concerns, but certainly this is very important to the field. The two clinical applications to date where it shows potential are periodontal disease and diabetic wounds. Maybe the reason for this is that both diseases result from a compromised or a defective healing environment.

The next step for the U-M team is to use the new gene delivery approach in human clinical trials, Giannobile said. The planning stages for these studies will commence in the next year.

The paper, called Adenovirus Encoding Human Platelet-Derived Growth Factor-B Delivered to Alveolar Bone Defects Exhibits Safety and Biodistribution Profiles Favorable for Clinical Use, is partially available online. It's scheduled to appear in the May issue of the journal Human Gene Therapy. Co-authors include Po-Chun Chang, Joni Cirelli, Yang-Jo Seol, Qiming Jin, Jim Sugai, Nisha D'Silva and Theodora Danciu. The study was supported by the National Institutes of Health and the AO Foundation.

Scientists closer to understanding how to control high blood sugar

Wed, 18 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich.---Scientists are closer to understanding which proteins help control blood sugar, or glucose, during and after exercise. This understanding could lead to new drug therapies or more effective exercise to prevent Type 2 diabetes and other health problems associated with having high blood sugar.

Insulin resistance happens when insulin produced by the body doesn't properly stimulate the transport of glucose into the cells for energy. Too much glucose in the bloodstream can cause a host of medical problems, including Type 2 diabetes, said Gregory Cartee, professor at the University of Michigan School of Kinesiology.

Insulin and muscle contractions are the two most important stimuli to increase glucose transport into muscle cells. Cells then use the glucose for energy. However, scientists aren't entirely sure how this works.

Cartee and colleague Katsuhiko Funai, a graduate student researcher in kinesiology, looked at how two different proteins believed to be important in stimulating glucose transport react to two different enzymes also related to glucose transport. The goal of the study was to understand the contribution of the two proteins, AS160 and TBC1D1, in skeletal muscle stimulated by insulin.

We're trying to rule out or rule in which proteins are important with exercise, Cartee said.

The results suggest that the protein TBC1D1 was more important for exercise-stimulated glucose transport and suggested that the second protein, AS160, might be less important for this effect of exercise. By focusing on the protein that works best---in this case, TBC1D---scientists can develop ways to make that protein work better for insulin-resistant people.

Insulin resistance is a huge public health problem that affects millions of people, Cartee said.

Almost all people with Type 2 diabetes have muscle insulin resistance, he said. This doesn't cause diabetes by itself, but it's an essential component that contributes to Type 2 diabetes. This impacts millions of people. Even for people who aren't diabetic, insulin resistance is associated with lots of health problems.

In the longer term, people who are insulin resistant, or whose muscle don't respond normally to insulin, are more likely to get Type 2 diabetes, Cartee said.

The muscles seems to have the machinery to respond to exercise, even though they aren't responding to insulin normally, he said. If we understood how exercise worked we could develop more effective exercise protocols. In others who can't exercise, we could figure out a drug therapy or something else for insulin control.

The next step is to study what exactly TBC1D1 does to promote glucose transport during and after exercise.

Team-based diabetes care fetches more value for dollar

Thu, 26 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Diabetes patients undergoing team-based care do not save more in treatment costs under Medicare and Medicaid than other patients, but they are healthier, according to a recent study.

Chronic conditions impose a substantial financial burden on patients, payers and employers, said Dennis Scanlon, professor of health policy and administration, Penn State, and lead author of the study. Assessing the financial impact of chronic care management strategies remains a key health policy issue.

The researchers compared Medicaid patients with diabetes who received team-based care with those who did not. The aim of the study was to determine whether multidisciplinary team-based care reduces medical payments and improves quality for the Medicaid enrollees.

Individuals with chronic conditions account for disproportionately high health cost and often experience losses in productivity, notes Scanlon. But on average these patients receive only 56 percent of recommended care according to recent studies.

The Penn State researchers analyzed data between 1997 and 2005 from Medicaid and Medicare claims and payments one year before and after intervention for patients at CareSouth, a federally qualified community health center serving 10 clinics in and around Hartsville, South Carolina.

Our analysis suggests that patients enrolled in the CareSouth program did not experience significantly lower total Medicare and Medicaid costs than similar patients who did not receive team-based care, said Scanlon, whose work is funded by the California Health Care Foundation.

Statistical analyses also suggest that over time there is significant improvement in systolic blood pressure, body mass index and hemoglobin A1C among CareSouth patients.

Scanlon finds the improvement in care without significant increases in drug costs and improvement in the body mass index unusual. He believes that better lifestyle management could be a reasonable explanation.

The researchers caution that the study was only able to include data for a short period of time after team-based care was initiated. Therefore, it is possible that a multi-year study could show longer-term savings associated with the program. Still, Our findings suggest that even if longer-term savings do not materialize, Medicaid and Medicare patients in this study received greater value for their dollars in the CareSouth sites after the intervention, Scanlon explained.

Scanlon and his colleagues first identified 199 patients with type 2 diabetes -- from a sample of 2,572 patients -- in whom the disease had been diagnosed less than a year before the start of intervention. The control group was 1,868 patients who had been diagnosed with the disease more than a year after intervention.

Our objective was to assess the impact of CareSouth's program on short-term Medicaid payments, as well as Medicare payments by those eligible for that Federal insurance program, and on key clinical diabetes indicators, explained Scanlon, whose findings appeared in a recent issue of

PAI-1 is the link between diabetes and cardiovascular disease

Wed, 25 Feb 2009 00:30:03 PST

( from http://www.rxpgnews.com ) Researchers at the University of Vermont Cardiovascular Research Institute, Colchester, Vermont have found that increased expression in the heart of plasminogen activator inhibitor type-1 (PAI-1) is profibrotic. The results, which appear in the March 2009 issue of Experimental Biology and Medicine, implicate PAI-1 overexpression, known to accompany insulin resistance and type 2 diabetes, as a factor contributing to the high incidence of heart failure after myocardial infarction in people with diabetes. The research team, Dr. A.K.M. Tarikuz Zaman, a research associate, Mr. Christopher J. French, medical and graduate student, Dr. David J. Schneider, Professor of Medicine and Director of the Cardiology and Vascular Biology Units, and Dr. Burton E. Sobel, Professor of Medicine and Director of the Cardiovascular Research Institute, performed studies in 10 week old mice subjected to coronary occlusion. Controls and PAI-1 overexpressing mice congenic on a C57BL6 background had comparable PAI-1 content in left ventricular myocardium despite a marked elevation of PAI-1 in plasma in the latter. 6 weeks after coronary occlusion the PAI-1 overexpressing mice exhibited a 2-fold increase in left ventricular (LV) PAI-1 content. Histochemical analysis demonstrated 33% more LV fibrosis as well. The increased fibrosis associated with increased PAI-1 was accompanied by functional derangements including diminished LV wall thickness in both diastole and systole, increased end systolic LV dimensions, depressed fractional shortening, a greater impairment of LV segmental function, and greater transmitral E-wave amplitude.

In summary, overexpression of PAI-1 in the heart altered the response of the left ventricle to myocardial infarction. It led to increased expression of PAI-1 late after coronary occlusion accompanied by increased fibrosis and functional derangements indicative of both systolic and diastolic dysfunction. Dr. Sobel said that "in concert with our previously reported findings demonstrating increased expression of PAI-1 in the heart in transgenic mice rendered insulin resistant, these results suggest that the markedly increased incidence and severity of heart failure following myocardial infarction in patients with insulin resistance and type 2 diabetes may reflect in part adverse consequences of increased PAI-1 expression in the heart predisposing to fibrosis and impairment performance of the left ventricle."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "these elegant studies by Dr. Sobel and colleagues provide substantial insight into the mechanisms by which type 2 diabetes, with the resulting increase in PAI-1 in the heart, can lead to increased incidence and severity of heart failure following myocardial infarction. This is a major step forward in our understanding of the linkage between diabetes and cardiovascular disease".

ORNL, UT project could save vision of millions

Tue, 17 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) OAK RIDGE, Tenn., Feb. 17, 2009 -- In the blink of an eye, people at risk of becoming blind can now be screened for eye diseases such as diabetic retinopathy and age-related macular degeneration.

Using a technology originally developed at the Department of Energy's Oak Ridge National Laboratory to understand semiconductor defects, three locations in Memphis have been equipped with digital cameras that take pictures of the retina. Those images are relayed to a center where they are analyzed and the patient knows in minutes whether he or she needs additional medical attention.

Once we've taken pictures of the eyes, we transmit that information to our database, where it is compared to thousands of images of known retinal disease states, said Ken Tobin, who led the ORNL team that developed the technology. From there, the computer system is able to determine whether the patient passes the screening or it provides a follow-up plan that includes seeing an ophthalmologist.

Already, this technology is making a difference as two patients at the Church Health Center in Memphis have been identified as needing laser treatment for moderate and severe diabetic retinopathy and macular edema, both conditions that can lead to blindness.

While some cameras have been installed, others will be installed at several rural and urban health care centers serving the Mississippi Delta. Another camera is planned for a federally funded health center in Chattanooga. Eventually, the goal is to have hundreds of cameras throughout the United States and beyond. If disease can be detected early, treatments can preserve vision and significantly reduce the occurrence of debilitating blindness.

This project takes advantage of ORNL's proprietary content-based image retrieval technology, which quickly sorts through large databases and finds visually similar images. For more than a decade manufacturers of semiconductors have used this technology to rapidly scan hundreds of thousands of tiny semiconductors to learn quickly about problems in the manufacturing process.

Our approach allows us to adapt a proven technology to describe key regions of the retina, and this information can then be used to index images in a content-based image retrieval library, Tobin said. What separates this from other methods is that we have automated the process of diagnosing retinal disease by capturing the expert knowledge of an ophthalmologist in a patient archive.

Leading the medical portion of the project is Edward Chaum, an ophthalmologist and Plough Foundation professor of retinal diseases at the University of Tennessee Health Science Center (

Type 2 diabetics with obstructive sleep apnoea- CPAP helps regulate nocturnal glucose levels

Mon, 15 Dec 2008 01:54:35 PST

( from http://www.rxpgnews.com ) A study in the Dec. 15 issue of the Journal of Clinical Sleep Medicine suggests that screening type 2 diabetes patients for obstructive sleep apnea (OSA) and treating those who have OSA with continuous positive airway pressure (CPAP) therapy could improve the management of their hyperglycemia and might favorably influence their long-term prognosis.

Results show that in a group of 20 type 2 diabetics who were mostly obese and were newly diagnosed with OSA, sleeping and nocturnal hyperglycemia were reduced and the sleeping interstitial glucose level was less variable during CPAP treatment. The average glucose level during sleep decreased by approximately 20 mg/dl after an average of 41 days of CPAP. The sleeping glucose also was more stable after treatment, with the median standard deviation decreasing from 20.0 to 13.0 and the mean difference between maximum and minimum values decreasing from 88 to 57.

According to Arthur Dawson, MD, senior consultant in the Division of Chest and Critical Care Medicine and co-director of research at Scripps Clinic Sleep Center in La Jolla, Calif., it is not surprising that many diabetics have sleep apnea since type 2 diabetes and OSA are both conditions that are becoming much more common because of the obesity epidemic.

Dawson said, "The low blood oxygen level and the arousals associated with an apneic event activate the sympathetic nervous system and cause the release of stress hormones, both of which tend to raise the blood glucose. If we could prevent these apneic events with CPAP then we might keep the glucose level lower and more stable through the night."

According to the authors, population surveys, the Wisconsin Sleep Cohort and the Sleep Heart Health Study estimate the prevalence of type 2 diabetes in patients with OSA to be about 15 percent. OSA is associated with increased insulin resistance independent of obesity; 50 percent of patients with OSA have type 2 diabetes or impaired carbohydrate metabolism.

Twenty patients with type 2 diabetes who were on a stable diabetic regime were recruited at the time of their initial consultation with a sleep physician. All participants were newly diagnosed with moderate to severe OSA, and none had any previous experience with CPAP. Glucose level was monitored with a continuous glucose monitoring system (CGMS) over a period of 36 hours, which included a night in a sleep laboratory for evaluation by polysmnography. On the first night of the study, patients' OSA was untreated. A second night of glucose monitoring and sleep recording was done after the participants had been on CPAP therapy for a duration of one-to-three months. No changes were made in participants' diets or medication for diabetes throughout the study.

The authors report that previous studies have shown that variability of the glucose level increases the risk of eye complications and death in type 2 diabetics. Dawson said that the authors believe that recognizing and treating sleep apnea could improve the outlook for diabetics who also suffer from OSA. Researchers involved in this study theorized that by using the CGMS they were able to pick up short-term changes in the glucose level that would not be detected by traditional measurements.

Diabetes and other sugar abnormalities have a relationship to sleep disturbances

Sun, 07 Dec 2008 13:53:03 PST

( from http://www.rxpgnews.com ) Diabetes and high levels of blood sugar may be linked to abnormalities in a person's body clock and sleep patterns, according to a genome-wide association study published in the journal Nature Genetics.

The research suggests that diabetes and higher than normal blood sugar levels could partly be tackled by treating sleep problems, say the researchers, from Imperial College London, the French National Research Institute CNRS, Lille University, McGill University in Canada, Steno Diabetes Centre in Denmark and other international institutions.

People with high blood sugar levels and diabetes have a greatly increased risk of developing a range of conditions, including cardiovascular diseases.

The new study shows that a mutation called rs1387153, near a gene called MTNR1B, is associated with having an increased average blood sugar level and around a 20 percent elevated risk of developing type 2 diabetes.

MTNR1B forms part of a signalling pathway that controls the action of the hormone melatonin. This hormone regulates the body's circadian rhythm - the internal clock that controls sleeping and eating patterns – by responding to daylight and darkness.

The discovery of the rs1387153 mutation provides evidence that high blood sugar and diabetes could be directly linked to an impaired circadian rhythm.

Professor Philippe Froguel, the corresponding author of the research from the Department of Genomic Medicine at Imperial College London, said: "There is already some research to suggest there are links between sleep problems and conditions such as obesity and depression, both of which are associated with diabetes. For example, we know that obese children tend to sleep badly and that people become more obese if they are not having enough sleep. Our new study demonstrates that abnormalities in the circadian rhythm may partly be causing diabetes and high blood sugar levels. We hope it will ultimately provide new options for treating people."

In healthy people, blood sugar levels are kept under control by insulin, which the pancreas releases in varying amounts at different periods during a 24-hour natural cycle. The researchers suggest that when there is a genetic abnormality that affects melatonin levels and sleep patterns, this may also disturb the levels of insulin in the blood, preventing the body from maintaining control of blood sugar levels.

Insulin is normally secreted in peaks during the daytime, in order to allow blood sugar from meals to be processed properly, and at lower levels at night. In contrast, melatonin levels are low during the daytime and high at night.

The new study is part of a series of discoveries about the genetics of diabetes made by Professor Froguel and his colleagues. In May 2008 they identified a genetic mutation that can raise the amount of sugar in a person's blood to harmful levels and in February 2007 they identified the key genes associated with a risk of developing type-2 diabetes in the first study to map the genes of any disease in such detail.

The new study shows that identifying which people have high numbers of genetic mutations can reveal who is at most risk of developing high blood sugar levels. On average, the more genetic mutations associated with high blood sugar levels people had, the higher their blood sugar level.

For example, people with five genetic mutations had an average fasting blood sugar level of 5.4, whereas people with one mutation had an average level of 5.12.

Forty three percent of those carrying six or more mutations had levels of fasting blood glucose of 5.6 mmol/l or more. This level is defined as being 'impaired' by the American Diabetes Association, meaning that such people have a very high risk of developing diabetes in the future.

Professor Froguel added: "We have been developing quite a clear picture of the key genes involved with high blood sugar and diabetes and this allows us to better understand them and suggest new avenues for treatment. We are also nearing the stage when we can develop tests that can identify the people at most risk of developing high blood sugar and diabetes later in their lives, so we can intervene to improve their health before they reach that point."

For the new study, the team analysed the genetic makeup of 2,151 non-diabetic French people (comprising 715 lean adults, 614 lean children, 247 obese adults and 575 obese children) and identified the rs1387153 mutation as being associated with high blood sugar levels. They confirmed their findings by looking at the genetic makeup of more than 16,000 non-diabetic people from different groups in France, Denmark and Finland.

The team then determined that the presence of the rs1387153 increased the risk of type 2 diabetes by comparing the genetic makeup of 6,332 French and Danish diabetic subjects with that of a group of 9,132 French and Danish people with normal blood sugar levels. The researchers found the same links between rs1387153 and a risk of diabetes in all the European populations they studied.

Genes for 9 health indicators

Sun, 07 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A new genome-wide study examines genetic variants associated with nine metabolic traits and is the first to draw out novel variants from a population unselected for current disease. The traits are indicators for common disease such as cardiovascular disease, type 2 diabetes, blood pressure, inflammation and lipid levels.

Cohorts are followed throughout their lives, gathering lifelong information about their health: these data will help researchers to dissect the complex causes of common disease, whether genetic or environmental. The current study might indicate genetic variants that influence early development of disease, informing public health measures.

Unlike case-control studies, which make genomic comparisons of apparently healthy people with patients with a specific condition, cohort studies provide long-term information across a population.

The power of studies such as ours lies in their ability to examine these traits for early life events, to reflect the genetic make-up of the wider population and to investigate the relationship between genetic variation and environment over time, says Professor Leena Peltonen, Head of Human Genetics at the Wellcome Trust Sanger Institute and a senior author of the paper. Our study indicates that the environment accounts for around 30% or less of the consequences of the traits. Clearly we have to increase our efforts to understand the genetic factors involved.

The population study looked at a cohort of people born in northern Finland in 1966: the environmental exposure and genetic background of this population is relatively homogeneous and, because the sample includes almost all people born in that year, it reflects the overall composition of the population.

The team looked at more than 360,000 genetic variants in almost 5000 people. These samples were typed to uncover variants associated with levels of triglycerides, high density lipoprotein, low density lipoprotein, glucose, insulin, C-reactive protein, as well as body mass index and blood pressure. Eight 'environmental' factors, including alcohol use, smoking and birth weight, were also included in the analysis.

We found 23 regions of the genome associated with these traits, says Professor Nelson Freimer, University of California, Los Angeles, the other senior author. We were delighted that our study identified 14 that had been described before: it is essential that a study such as this picks up the known variants.

More important, we found nine novel variants: in five of these cases, our knowledge of the role of the gene suggests they are good candidates for important variants.

The research differs from prior investigations in power and study design, which might explain its ability to identify nine previously unknown loci. Five of these associations - HDL with NR1H3 (LXRA), LDL with AR and FADS1/FADS2, glucose with MTNR1B, and insulin with PANK1 - implicate genes with known or postulated roles in metabolism, and are good candidates for further study of the biological role they might play in these conditions.

The comprehensive cohort study also allowed the team adjust for the additional data such as environmental influences and body mass index. Three regions were associated with LDL or insulin when the population was divided into normal or elevated body mass index.

Our population sample allows us to look at gene-environment interactions, explains Professor Chiara Sabatti, University of California, Los Angeles, a co-author of the paper, but we need to examine larger populations in order to validate these. We are only starting to have a glimpse of how the power of modern genetics can work with population data to uncover genes that will be able to help clinical and public health work in the future. We still have many challenges ahead.

Although genetic influences are thought to account for at least half of the variation in each of the traits, the current results explain perhaps one-tenth of that. There remains much more to be discovered.

Work underway, such as The 1000 Genomes Project and wider population studies, will help to determine whether the additional genetic effects lie in many common variants with relatively small effect or in rare variants with a larger effect.

New technique eliminates toxic drugs in islet transplant in diabetic mice

Thu, 20 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO -- The body's immune system hates strangers. When its security patrol spots a foreign cell, it annihilates it.

This is the problem when people with type 1 diabetes undergo human islet cell transplantation. The islet cells from a donor pancreas produce robust amounts of insulin for the recipient -- often permitting independence from insulin therapy. However, the immune system tries to kill the new hard-working islets.

A person who has the transplant procedure must take powerful immunosuppressive drugs to prevent their bodies from rejecting the cells. The drugs, however, are toxic to the new islet cells and put patients at risk for infections and cancer.

Now researchers at Northwestern University's Feinberg School of Medicine have found a way to trick the immune system of mice into believing those transplanted islets are its own cells. This new technique eliminated the need for the immunosuppressive drugs in mice with chemically-induced diabetes after they had islet transplantation.

We made the recipient feel that the donor cells are their own, explained Stephen Miller, co-principal investigator and the Judy Gugenheim Research Professor of Microbiology-Immunology at the Feinberg School. This technique is a highly attractive potential therapy for human islet cell transplantation. The findings were reported in the journal Proceedings of the National Academy of Science in the fall.

As many as 3 million people in the U.S. may have type 1 diabetes, a disease that develops in children and adolescents. There are about 50 to 70 islet transplants, an experimental procedure, annually in North America.

Miller said he was happily surprised to see that such a high percentage of recipients of the transplanted islet cells -- greater than 70 percent -- maintained transplants long-term. His research showed the host's tolerance to these transplanted cells seemed to be permanent, lasting for at least 150 days. Xunrong Luo, assistant professor of medicine in nephrology at the Feinberg School, was co-principal investigator for the study.

In the study, researchers took a type of white blood cell from the islet donor's spleen, called splenocytes, and treated them with a chemical that masked the cells' identity. They then injected these chemically treated cells into diabetic mice before and after the mice underwent islet cell transplantation. As a result, the immune system of the mice didn't try to reject the cells, because it didn't perceive them as foreign and dangerous.

When the same test was done without pre-treated cells, the immune system rejected the transplanted islets within 15 days.

In an upcoming study, Miller and Luo will work with mice that have autoimmune disease that destroys their islet cells, as occurs in type 1 diabetes. Researchers will use therapies that prevent the autoimmune system's response against its own beta cells (which are part of the islets) as well as prevent the recipient's immune responses against the transplanted islet cells.

We have ways we can do both, Miller said. Hopefully this next study will show we can take combined therapies for underlying autoimmune disease and transplanted islets. If we do that together, we hopefully can cure an animal who became diabetic from autoimmune disease. If successful, the next step would be testing the technique on human subjects.

Miller said this technique also has applications for treating other autoimmune diseases such as multiple sclerosis.

Pure insulin-producing cells produced in mouse

Thu, 20 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Singapore researchers have developed an unlimited number of pure insulin-producing cells from mouse embryonic stem cells (ESCs).

These pure insulin-producing cells, which according to electron microscopy studies, have the same sub-cellular structures as the insulin-producing cells naturally found in the pancreas, were highly effective in treating diabetes in the mouse model.

The transplants of pure insulin-producing cells reduced the blood glucose levels of diabetic mice with high blood glucose levels.

The experiments also showed that the subsequent removal of the transplanted cells from the diabetic mice restored the blood glucose to its original high level.

None of the diabetic mice involved in the transplant experiments developed teratoma, which are a type of tumour often associated with ESCs and which could complicate their use in human therapeutic treatment.

Furthermore, the pure insulin-producing cells managed to retain their insulin-production and glucose-sensing capacity over time.

The Singapore researchers' achievement provides proof of principle that this strategy could be applied to human ESCs to obtain similar pure insulin-producing cells.

These research findings were published in two separate papers in the July and August 2008 online versions of the journal Stem Cell Research.

Conducting the research were scientists at the Institute of Medical Biology (IMB), which is under Singapore's Agency for Science, Technology and Research (A*STAR), and the Yong Loo Lin School of Medicine (YLLSoM ) at the National University of Singapore (NUS).

The team of researchers was co-led by Dr. Lim Sai Kiang, an IMB principal investigator and a research associate professor at the YLLSoM Department of Surgery, and Dr. Li Guodong, a research associate professor at National University Medical Institutes, YLLSoM, NUS.

Commenting about these findings, Dr. Gordon Weir, Director of the Clinical Islet Transplantation Program at Harvard Medical School, who also holds appointments at the Harvard Stem Cell Institute and Joslin Diabetes Centre, said, The amount of careful work done by this group of researchers is impressive. We need something to put into diabetic patients to treat their condition, and these findings tell us interesting things about the development of beta cells.

The strategic approach by the group offers avenues for further research in the treatment for diabetes. Said Dr. Lim, Our ability to isolate and then multiply insulin-producing cells from differentiating ESCs provides an unlimited supply of pure insulin-producing cells to study in unprecedented detail many aspects of these cells.

Added Dr Li, Besides providing a tool to facilitate basic research in test tubes and animals, these insulin-producing cells may be also used to replace the isolated native pancreatic cells that are hard to obtain in a large amount, for pharmacological tests.

Teaching tools foster science and diabetes education in Native-American schools

Wed, 12 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Schools across the country now have free access to an innovative set of teaching tools designed to increase the understanding of science, health, and diabetes among American Indian and Alaska Native students from kindergarten through the 12th grade. The comprehensive new curriculum, called Health is Life in Balance, is being launched today at the Smithsonian's National Museum of the American Indian in Washington, D.C.

The curriculum, a product of the Diabetes-based Science Education in Tribal Schools (DETS) program, integrates science and Native American traditions to educate students about science, diabetes and its risk factors, and the importance of nutrition and physical activity in maintaining health and balance in life. Applying an inquiry-based approach to learning, the curriculum builds research skills in observation, measurement, prediction, experimentation, and communication. The project was developed in collaboration with eight tribal colleges and universities and several Native American organizations, with funding from the National Institutes of Health (NIH), the Indian Health Service (IHS), and the Centers for Disease Control and Prevention (CDC).

Diabetes, a major cause of heart disease and stroke and the most common cause in adults of blindness, kidney failure, and amputations not related to trauma, now afflicts nearly 24 million people in the United States. Type 2 diabetes, the most common form of the disease, is linked to older age, obesity, physical inactivity, family history of the disease, and a history of gestational diabetes. In the last 30 years, the incidence of type 2 diabetes has been steadily rising.

The rate of diagnosed diabetes in American Indians and Alaska Natives is two to three times that of non-Hispanic whites. Nearly 17 percent of the total adult population served by the IHS has diagnosed diabetes. After adjusting for population age differences, diabetes rates vary from 6 percent among Alaska Native adults to 29 percent among American Indian adults in southern Arizona. Once seen only in adults, type 2 diabetes is increasingly being diagnosed in youth, especially in American Indian and other minority populations.

Many people don't know that type 2 diabetes can often be prevented by losing a modest amount of weight through diet and regular physical activity, said Griffin P. Rodgers, M.D., director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which contributed most of the funding for the project. We hope that this innovative, well tested curriculum will reduce the rapidly rising incidence of type 2 diabetes in Native Americans by teaching young people about diabetes prevention.

Alvin Windy Boy, former chair of the Tribal Leaders Diabetes Committee, a group of elected tribal officials who advise the Indian Health Service on diabetes topics, voiced the need for the curriculum at a 2002 meeting of the Diabetes Mellitus Interagency Coordinating Committee (DMICC), which coordinates federal research and activities related to diabetes. The materials were designed and extensively tested by staff in eight tribal colleges and universities, who worked with 63 teachers and 1,500 students in schools across 14 states. This curriculum is an important step in educating American Indian and Alaska Native youth about preventing type 2 diabetes. The materials are understandable, tailored for students at different grade levels, and make the concepts relevant to our lives and families, said Windy Boy.

We're pleased that our native youth will now be learning how to prevent type 2 diabetes early in life and in their own schools. We hope some of these students will be inspired to become health professionals to help us in the fight against diabetes and other chronic diseases, added Buford Rolin, who now chairs the Tribal Leaders Diabetes Committee.

The curriculum units provide accurate, culturally tailored materials and lesson plans for use in more than 1,000 tribal schools on reservations and in public schools that have a sizable number of Native American students. This curriculum can change perceptions and attitudes about diabetes and empower young people to adopt healthier lifestyles, said Kelly Acton, M.D., M.P.H, director of the Division of Diabetes Treatment and Prevention of the IHS, which will oversee distribution to schools.

To order printed copies or CDs of the curriculum free of charge, see the IHS website

University of Miami biomedical engineer wins

Wed, 12 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) CORAL GABLES, FL (November 12, 2008)-Cherie L. Stabler, Ph.D., assistant professor in the University of Miami College of Engineering and director of the tissue engineering program at the Diabetes Research Institute at the University of Miami Miller School of Medicine, is one of only ten scientists across the country to win the Type 1 Diabetes Pathfinder Award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The award recognizes highly innovative research studies that offer exceptional promise for improving the understanding, prevention and treatment of Type 1 diabetes and its complications.

The recipients, all new researchers who have never been principal investigators on an NIH-funded grant, receive about $1.5 million each in direct costs to pursue their work over a five-year period.

The Pathfinder Award recognizes creative new investigators whose innovative projects have the potential for unusually high impact in Type 1 diabetes, said NIDDK Director Griffin P. Rodgers, M.D. With this award, we hope to attract and retain talented new investigators whose bold and promising ideas have the potential to revolutionize thinking about type 1 diabetes.

The project for which Stabler won her award is titled Functionalized, Nanoscale Coatings for Islet Encapsulation. The proposal is focused on improving clinical islet transplantation, currently considered the most promising method for curing diabetes, by overcoming the impaired function and loss of islets following implantation.

Islet loss following transplantation is attributed to a strong inflammatory and immunological response by the patient to the transplant that we know is triggered by markers on the surface of the cell, explains Stabler.

Her research seeks to use novel biomaterials to encapsulate the islet cells and protect them from these detrimental responses by masking, or camouflaging, the cell surface. The work is focused on creating capsules on the nano-scale, as opposed to the current methods that create micro-scale coatings.

Given the high metabolic demand of these cells, we cannot place large biomaterial barriers between the islets and their nutrient supply or we basically starve the encased cells, explains Stabler. By minimizing the barrier thickness from micron to nano-scale, it's basically like shrinking that barrier from the size of a football field to a couple of blades of grass.

Dr. Stabler serves as an assistant professor of biomedical engineering in UM's College of Engineering, with a secondary appointment in the Department of Surgery at the Miller School, and her laboratory is at the Diabetes Research Institute on the medical campus. The collaboration between the College of Engineering and the Miller School of Medicine is part of an ongoing effort to forge interdisciplinary cooperation with the goal of making groundbreaking scientific discoveries.

Dr. Stabler's award is the first reward of our recently increased cooperation between the College of Engineering and the Miller School of Medicine, said Ozcan Ozdamar, PhD., professor and chairman of the Department of Biomedical Engineering. Dr. Ricordi saw the advantage of working together to find innovative solutions to challenging medical problems, and collaborated with us to recruit Dr. Stabler, who is an excellent bioengineer and diabetes researcher with a bright future.

Camillo Ricordi, M.D., serves as the scientific director of the Diabetes Research Institute, and leads an exceptional team of investigators focused on finding a cure for Type 1 diabetes.

Dr. Stabler's area of research is at the forefront of one of our major strategic objectives, where cellular therapies and regenerative medicine meet tissue engineering and nanotechnologies, said Ricordi. We are proud to have been able to recruit such a distinguished investigator who has already proven to be a key asset of our team-based search for a cure.

International Diabetes Federation calls for global action to keep all children with diabetes alive

Mon, 13 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The International Diabetes Federation (IDF) announced today that it is bringing together key opinion leaders to push for action to secure care for the thousands of children with diabetes in developing countries without access to care.

The meeting, Access to Essential Diabetes Medicines for Children in the Developing World, will be held on Saturday, October 25 in London, United Kingdom. The International Diabetes Federation has invited Ministries of Health from various developing countries, leaders from the pharmaceutical industry, philanthropic foundations, leading supply-chain management firms, diabetes associations, as well as professional societies in paediatrics and diabetes education.

We are bringing together the people and the organizations that can provide not only the interim humanitarian response to save lives but can lay the groundwork for sustainable solutions that will benefit all children with diabetes, said Dr Martin Silink, President of the International Diabetes Federation (IDF).

Diabetes is one of the most common chronic diseases to affect children. Every day more than 200 children are diagnosed with type 1 diabetes, requiring them to take multiple daily insulin shots and monitor the glucose levels in their blood. It is increasing at a rate of 3% each year among children and rising even faster in pre-school children at a rate of 5% per year. Currently, over 500,000 children under the age of 15 live with diabetes.

For children in the developing world with type 1 diabetes, the picture is bleak. Close to 75,000 children in low-income and lower-middle income countries are living with diabetes in desperate circumstances. These children need life-saving insulin to survive. Even more children are in need of the monitoring equipment, test strips and education required to manage their diabetes and avoid the life-threatening complications associated with the disease. A child's access to appropriate medication and care should be a right not a privilege.

The stark reality is that many children in developing countries die soon after diagnosis, said Dr Jean-Claude Mbanya, President-Elect of the International Diabetes Federation. It's been 87 years since the discovery of insulin, yet many of the world's most vulnerable citizens, including many children, die needlessly because of lack of access to this essential drug. This is a global shame. We owe it to future generations to address this issue now.

In many developing countries, particularly in Sub-Saharan Africa and some parts of Asia, life-saving diabetes medication and monitoring equipment is often unavailable or unaffordable. As a result, many children with diabetes die soon after diagnosis, or have poor control and quality of life, and develop the devastating complications of the disease early.

In order to support some of those children, the International Diabetes Federation created its Life for a Child Program in 2001. The program, which is operated in partnership with Diabetes Australia-NSW and HOPE worldwide, currently supports a total of 1000 children in Azerbaijan, Bolivia, The Democratic Republic of Congo, Ecuador, Fiji, India, Mali, Nepal, Nigeria, Papua New Guinea, The Philippines, Rwanda, Sri Lanka, Sudan, The United Republic of Tanzania, Uzbekistan and Zimbabwe.

The 1000 children that we support represent a pitifully small number of those in need, said Dr. Silink, who co-founded the Program. It seems unthinkable that diabetes care remains beyond the reach of so many. Solutions are available now to address the issues of affordability and accessibility. The means exist to strengthen healthcare systems and provide the diabetes education of healthcare professionals and the families of those affected by diabetes to make a significant step forward.

The timing of the London meeting is no accident, falling as it does just ahead of World Diabetes Day, November 14. The theme of the United Nations Health Day is diabetes in children and adolescents. The campaign led by the International Diabetes Federation with the endorsement of the World Health Organization sets out to establish the message that no child should die of diabetes.

Einstein and Montefiore receive grants to expand disease-focused stem cell research

Fri, 03 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The Empire State Stem Cell Board has awarded research planning grants to Albert Einstein College of Medicine and to Montefiore Medical Center. The grants, totaling $238,000, are part of $2 million in grants announced by State Health Commissioner Richard F. Daines, M.D. The funding, awarded to 18 medical colleges, medical centers and labs will strengthen New York State's capacity for stem cell research and could lead to the development of new therapies for Alzheimer's, diabetes, Parkinson's, ALS and other conditions.

Allen M. Spiegel, M.D., the Marilyn and Stanley M. Katz Dean said, Einstein considers this grant an important step in working collaboratively with scientists across New York State to broaden our understanding of stem cells. This knowledge could lead to breakthroughs in medical science that will have important implications for people suffering from many devastating diseases.

The ability to treat and heal patients with serious conditions such as liver disease and cancer through groundbreaking stem cell treatments represents the future of medicine, and it is very exciting for us to be part of this vital statewide initiative, said Steven M. Safyer, M.D., President and CEO of Montefiore Medical Center. Montefiore welcomes the opportunity to bring its strengths to this collaboration and create the synergy between biomedical advancement and its applications to patient care that can happen only in a premier academic medical center like ours.

The planning grant awarded to Montefiore will focus on the liver, which has a unique capacity for regeneration. Liver-directed cell therapy offers opportunities to treat or cure dozens of diseases where the liver itself is damaged or diseases that have a basis in the liver but result in disease in other organs of the body. This program will permit progress in developing new treatments for liver failure, genetic diseases and other disorders which can be addressed by such therapy.

The planning grant awarded to Einstein will focus on establishing a consortium for blood cell disease in New York State. Eric Bouhassira, Ph.D., Einstein's Ingeborg and Ira Leon Rennert Professor of Stem Cell Biology and Regenerative Medicine, said, What we're hoping to do is to create unique stem cells derived from patients with blood diseases like sickle cell anemia and hemophilia. Once we have these stem cells, we will be in a much better position to try to cure them, by either correcting the genes that cause the problem or by developing drugs that treat the underlying cause of these diseases.

Grant money received to date is part of a coordinated effort by both institutions to ramp up research and improve methods for deriving stem cell lines. The planning grants will allow Einstein and Montefiore to compete for much larger grants in the future.

In January, the Empire State Stem Cell Board awarded Einstein and Montefiore combined first-phase grants of more than $1 million. That funding supports activities at Einstein's Gottesman Institute for Stem Cell and Regenerative Medicine Research and at Montefiore. The two institutions work as partners conducting rigorous scientific study and developing novel therapies for patients.

With support from the Empire State Stem Cell program we can share our knowledge, leverage capabilities with other top medical researchers and clinicians, and increase our opportunities to discover and develop new treatments for a variety of clinical conditions and diseases, said Brian Currie, M.D., Vice President of Research at Montefiore.

Under the Empire State Stem Cell program, Einstein and Montefiore work within consortia aimed at linking research institutions and corporations, building and strengthening interdisciplinary research teams, establishing core research facilities, and developing stem cell training and education programs. Stem cell research aims to improve human health and alleviate disease by restoring cells, tissues, and organs lost to disease or injury. There are many areas in medicine where stem cell research could have a significant impact, particularly where a patient's cells or tissues are destroyed and must be replaced by tissue or organ transplants. Researchers believe that stem cell research also holds promise in treating and potentially curing diseases for which there are currently no adequate therapies.

The Empire State Stem Cell Trust Fund, created by the 2007-2008 state budget, will provide up to $600 million for stem cell research over 11 years, an allocation second only to that of California.

High blood pressure takes big toll on small filtering units of the kidney

Fri, 19 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Take a kidney out of the body and it still knows how to filter toxins from the blood.

But all bets are off in the face of high blood pressure.

How does the kidney know how to do it and why does it break in hypertension? says Dr. Edward W. Inscho, physiologist in the Medical College of Georgia Schools of Medicine and Graduate Studies.

The kidneys filter about 200 quarts of plasma daily, eliminating about two quarts of waste product and extra water as urine, according to the National Institute of Diabetes and Digestive and Kidney Diseases. But the complete physiology remains a mystery.

He challenged colleagues to fill in important blanks in how this process works normally and how to make it work better in disease during the Sept. 19 Lewis K. Dahl Memorial Lecture at the 62nd High Blood Pressure Research Conference and Workshop in Atlanta.

One thing is clear: Hypertension takes a serious toll on the kidneys and damaged kidneys worsen hypertension. Dr. Inscho believes the kidneys' million hard-working filters, or glomeruli, are direct victims of high pressure. His research focuses on the minute arteries, or arterioles, that feed blood into each of them. These afferent arterioles are responsible for keeping blood pressure at a comfortable 60 mmHg inside glomeruli. At a healthy blood pressure of 120/80 mmHg, blood enters the artery at a mean pressure of 100 mmHg, but higher pressures mean the arterioles must work even harder to reach the 60 mmHg target. They seem up to the task at least initially, contracting to make it harder for blood to pass and reducing pressure in the process. We want to know how it does that, Dr. Inscho says as he watches the near instantaneous contraction.

He thinks he may at least know the messenger. The first reaction to high pressure actually is for the small vessel to stretch. That stretch prompts smooth muscle cells on the vessel wall to release ATP, a common molecule known as an energy source but also gaining acceptance as an extracellular messenger, he theorizes. It's an action-reaction kind of event.

When he puts ATP on the vessel it rapidly constricts; when he blocks the ATP receptor it won't. Unfortunately ATP works best in the face of normal pressures: constricting pressure about 25 percent as opposed to 2-3 percent when it's high. Still there are plenty of questions. Whether ATP is really released by the initial stretching is a critical one, he says. Whether ATP really comes from smooth muscle cells is another.

University of Southern California researcher Dr. Janos Peti-Peterdi thinks high pressures tugging the tethers connecting smooth muscle cells to others in the blood vessel wall may really be what releases ATP, a theory Dr. Inscho presented during the Sept. 19 meeting. It may be that hypertension changes the attachment of those tethers so they don't respond and the blood vessel can't either.

We are trying to figure out how all this fits together, says Dr. Inscho. Figuring out the critical steps of this amazingly elegant, amazingly precise and very complicated process will lead to better understanding of what gets corrupted by diseases such as hypertension and diabetes and maybe how to stop kidney destruction.

As scientists are finding with many diseases, Dr. Inscho says inflammation likely plays a big role. We know we can make these animals hypertensive, treat them with anti-inflammatories and prevent this whole process from occurring, he says of glomeruli destruction. I think that's pretty exciting, but we don't know exactly how we are doing that. Blood pressure is not affected, just the negative impact on the kidneys. Inflammation, he notes, is likely well-intended but ultimately ends up thickening blood vessel walls and hampering flexibility.

Type 1 diabetes may result from good genes behaving badly

Fri, 19 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) WHAT: New research from Stanford University scientists suggests that type 1 diabetes, an autoimmune disease that develops in children and young adults, may not be due to bad genes but rather to good genes behaving badly.

Because type 1 diabetes typically runs in families, scientists have looked for inborn genetic errors or gene variants passed on from generation to generation. Although this search has failed to find a single type 1 diabetes gene, many candidate type 1 diabetes susceptibility genes have been identified. These susceptibility genes, located in a region known as the major histocompatibility complex (MHC), help the body distinguish its own cells and tissues from those that are foreign.

Studies in identical twins, however, reveal that the situation is more complicated: often one twin develops type 1 diabetes while the other twin remains disease-free. This pattern of good luck/bad luck led researchers at Stanford to examine whether genetically at-risk individuals respond differently to environmental stimuli. In some cases, the immune system will respond in a benign fashion, while in other cases it will begin an inflammatory response that can ultimately lead to diabetes. The critical difference between health and disease might thus reside not in an individual's genetic blueprint but in how those genes are expressed--that is, how the translation of genetic information into proteins or RNA is switched on and off.

In a study supported by the National Institute of Allergy and Infectious Diseases, (NIAID) part of the National Institutes of Health, the Stanford team, led by C. Garrison Fathman, M.D., studied differences in gene expression between two groups of mice. The first group, non-obese diabetic mice, spontaneously develop type 1 diabetes. The second group, mice genetically identical to the first group except for their MHC genes, do not develop the disease. The researchers looked at gene expression in three different tissues in the diabetic and non-diabetic mice at separate times after birth. In the first few weeks of life, they found an explosion of changes in gene expression in the pancreatic lymph nodes, spleen and circulating blood cells of the diabetic mice compared with those in the non-diabetic mice. At 8 weeks, this activity had quieted down. But several weeks later, when the mice were 12 weeks old, a second explosion of changes in gene expression occurred in the diabetic mice in all three tissues examined: pancreatic lymph nodes, spleen and blood cells.

According to Dr. Fathman, the results suggest that type 1 diabetes may not result from genetic mutations but from differences in how normal genes and gene variants are turned on and off during disease progression. In addition to identifying altered genes that may indicate potential avenues for therapeutic or preventive treatments, the authors also found patterns of coordinated gene expression that may prove useful as biomarkers of disease onset or progression.

Presidential medal for technological breakthroughs earned by 2 chemical engineering professors

Wed, 27 Aug 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Two chemical engineering professors from The University of Texas at Austin have been recognized by President George W. Bush as 2007 National Medal of Technology and Innovation laureates, the nation's highest honor for technological achievement.

In a rare recognition of two honorees from the same institution for separate discoveries, Professors Adam Heller and Grant Willson were among eight national recipients announced this week.

It's sort of the American Nobel Prize, says Richard Maulsby, spokesman for the United States Patent and Trademark Office, which administers the Medal program.

Heller was cited for his contributions to electrochemistry and bioelectrochemistry which led to the development of products that have improved the quality of life of millions, particularly in the area of human health and well-being. Heller's work enabled the creation of the painless glucose monitor for diabetics.

Willson, who holds the Rashid Engineering Regents Chair at the Cockrell School of Engineering, was cited for creating lithographic imaging materials and techniques that have enabled the manufacturing of smaller, faster and more efficient micro-electronic components.

With unprecedented consistency and creativity, these two engineers have spent careers continually besting their own breakthroughs, says Ben Streetman, dean of the Cockrell School of Engineering. Their pioneering ability to link disciplines taught a new generation of researchers the value of reaching outside of their knowledge base to solve problems. It has been a great privilege of my career to witness their simultaneous contribution to research, education and society.

Roger Bonnecaze, Chemical Engineering Department chairman, says the dual recognition is a monumental achievement for the Cockrell School of Engineering and the department.

To have two winners from the same department, let alone the same university is exceptional, he says. These awards are extremely well deserved and are for two unique and creative contributions to technology. Heller's development of glucose biosensors has revolutionized diabetes care, improving the lives of millions of people, and created a billion dollar business (Abbott Diabetes Care, formally Therasense) employing several thousand people. Willson's innovative work on lithography for microelectronics has enabled many of the electronic devices we enjoy today and will enjoy in the future and is spawning new nanomanufacturing industries, such as Molecular Imprints in Austin.

The last University of Texas at Austin recipient was George Kozmetsky in 1993.

Established by an act of Congress in 1980, the medal was first awarded in 1985. It's awarded annually to individuals, teams, companies or divisions of companies for their outstanding contributions to the nation's economic, environmental and social well-being through the development and commercialization of technological products, processes and concepts; technological innovation; and development of the nation's technological manpower.

Laureates will receive their medals in a formal awards ceremony at the White House on Sept. 29 in the East Room.

Caesarean babies more likely to develop diabetes

Tue, 26 Aug 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Babies delivered by Caesarean section have a 20 per cent higher risk than normal deliveries of developing the most common type of diabetes in childhood, according to a study led by Queen's University Belfast.

The team, led by Dr Chris Cardwell and Dr Chris Patterson, examined 20 published studies from 16 countries including around 10,000 children with Type 1 diabetes and over a million control children.

They found a 20 per cent increase in the risk of children born by Caesarean section developing the disease. The increase could not be explained by factors such as birth weight, the age of the mother, order of birth, gestational diabetes and whether the baby was breast-fed or not, all factors associated with childhood diabetes in previous studies.

Dr Cardwell, from the School of Medicine, Dentistry and Biomedical Sciences, said: This study revealed a consistent 20 per cent increase in the risk of Type 1 diabetes. It is important to stress that the reason for this is still not understood. It is possible that children born by Caesarean section differ from other children with respect to some unknown characteristic which consequently increases their risk of diabetes, but it is also possible that Caesarean section itself is responsible.

Type 1 diabetes occurs when the immune system destroys the insulin producing cells in the pancreas, and one theory suggests that being born by Caesarean section may affect the development of the immune system because babies are first exposed to bacteria originating from the hospital environment rather than to maternal bacteria.

Dr Chris Patterson said: The study findings are interesting, but unless a biological mechanism is established it would be unwise to read too much into this association between Caesarean section delivery and diabetes.

Fortunately figures from the Northern Ireland Type 1 diabetes register indicate that only around two per 1,000 children will develop diabetes by their 15th birthday so a 20 per cent increase is on quite a low baseline risk.

Diabetes is a serious condition that, if not managed, can lead to fatal complications including heart disease, stroke, kidney failure and amputations. There are 2.3 million people in the UK diagnosed with diabetes and 250,000 with Type 1 diabetes. In Northern Ireland over 62,000 people have diabetes, 6,000 of them with Type 1 diabetes.

Around one in four babies in Northern Ireland are delivered by Caesarean section, which is significantly higher that the World Health Organisation's recommended rate of 15 per cent.

Iain Foster, Director of Diabetes UK Northern Ireland, said: Not all women have the choice of whether to have a Caesarean section or not, but those who do may wish to take this risk into consideration before choosing to give birth this way.

We already know that genetics and childhood infections play a vital role in the development of Type 1 diabetes in children, but the findings of this study indicate that the way a baby is delivered could affect how likely it is to develop this condition later in life. Diabetes UK Northern Ireland would welcome more research in this area.

insulin-producing cells can give rise to stem-like cells in-vitro

Mon, 21 Jul 2008 23:22:55 PST

( from http://www.rxpgnews.com ) The question of whether insulin-producing cells of the pancreas can regenerate is key to our understanding of diabetes, and to the further development of regenerative therapies against the disease. Dr Rosenberg from the McGill University Health Centre (MUHC) and McGill University together with Dr Bernard Massie from the Centre hospitalier de l'Université de Montréal (CHUM) have just concluded that they can. The results of their study have been published in the July issue of the journal Laboratory Investigation.

The researchers have shown in vitro that insulin-producing β-cells (beta cells) can return to a more primitive developmental state called stem-like cells. This process is known as "dedifferentiation" and highlights the plasticity of this cell type. This same result has also been validated for the three additional types of cells that – along with β-cells – make up the islets of Langerhans. Together, these islet cells produce insulin and other hormones in the pancreas.

"The potential for dedifferentiation of all the different cells that make up the islets of Langerhans is a totally new finding," Dr. Rosenberg said.

"At this stage, we can't confirm whether the cells' ability to turn into stem-like cells occur naturally in a healthy pancreas, but the results are very encouraging for the development of regenerative therapies to fight diabetes," he continued. The cell's in-vitro plasticity opens up totally new avenues of investigation into the underlying causes of diabetes, and will validate the development of innovative treatments.

This study is the latest step in an extensive regenerative therapies research program based on a peptide called Islet Neogenesis Associated Protein, or INGAP. Dr. Rosenberg and his colleagues have demonstrated INGAP's potential to induce new islet formation in the pancreas. Clinical trials with INGAP have already demonstrated that it is possible to regrow new functional insulin-producing cells in diabetic patients.

"We know that the peptide works, but we are still lacking certain theoretical bases to explain its mechanism," said Dr. Rosenberg. "This finding will allow us to move ahead on firmer ground."

Racial disparities exist among diabetes patients treated by the same physician

Mon, 09 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Black patients with diabetes are less likely than white patients to achieve long-term control of their blood glucose, blood cholesterol and blood pressure levels, even when they are treated by the same physician, according to a report in the June 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Racial disparities in the quality of diabetes care have been previously documented, according to background information in the article. Black patients with diabetes are less likely to receive recommended components of care, including hemoglobin A1C testing (HbA1C, a measure of blood glucose control over time) and lipid testing, and to achieve treatment goals, such as controlled blood pressure, cholesterol and blood glucose levels. In addition, black patients are more likely than white patients to develop diabetes-related eye and kidney disease and to have amputations of their lower extremities. Identifying the underlying reasons and potential solutions for these differences in quality of care and outcomes is a high priority, the authors write.

Thomas D. Sequist, M.D., M.P.H., of Harvard Vanguard Medical Associates, Boston, and colleagues analyzed electronic medical records from 4,556 white patients and 2,258 black patients with diabetes treated by 90 primary care physicians in eastern Massachusetts. Each physician treated at least five black patients and five white patients; all patients were age 18 or older and had visited the physician within the last two years.

Black patients and white patients received tests of low-density lipoprotein (LDL or bad) cholesterol and HbA1C at similar rates. However, white patients were more likely than black patients to reach commonly accepted benchmarks for controlled levels of HbA1C (47 percent vs. 39 percent), LDL cholesterol (57 percent vs. 45 percent) and blood pressure (30 percent vs. 24 percent).

Patient sociodemographic factors explained 13 percent to 38 percent of the racial differences in these measures, whereas within-physician effects accounted for 66 percent to 75 percent of the differences, the authors write. Thus, racial differences in outcomes were not related to black patients differentially receiving care from physicians who provide a lower quality of care, but rather that black patients experienced less ideal or even adequate outcomes than white patients within the same physician panel.

The variation in diabetes care was not related to overall performance or the volume of black patients treated by individual physicians, the authors note. Our data suggest that the problem of racial disparities is not characterized by only a few physicians providing markedly unequal care, but that such differences in care are spread across the entire system, requiring the implementation of system-wide solutions, they write. Efforts to eliminate these disparities, including race-stratified performance reports and programs to enhance care for minority patients, should be addressed to all physicians.

(Arch Intern Med. 2008;168[11]:1145-1151. Available pre-embargo to the media at

An Australian-led diabetes study shows intensive glucose control reduces serious complications

Mon, 09 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) An Australian led global study, the largest of its kind, has found that the risk of developing serious kidney disease and other complications amongst our 1.2 million people living with diabetes can be significantly reduced by intensively lowering blood glucose (sugar) levels beyond what is currently standard practice.

The ADVANCE (Action in Diabetes and Vascular Disease) study was conducted by the Sydney based George Institute for International Health involving more than 11,000 people with type 2 diabetes worldwide.

The results show that intensive blood glucose (sugar) control using modified release gliclazide and other drugs as required, protects patients against serious complications of the disease. In particular, intensive treatment reduces the risk of kidney disease by one-fifth.

Presented today by Australian researchers at the American Diabetes Association conference in San Francisco and published in the New England Journal of Medicine, the results of ADVANCE show that this intensive treatment strategy has the potential to benefit millions of diabetic patients worldwide.

Diabetes mellitus is one of the greatest threats to the health of populations worldwide. More than 1 million Australians and over 250 million people globally are living with diabetes and that number is estimated to rise to 380 million in 2025.

Chief investigator of the study, Professor Stephen MacMahon, Principal Director of The George Institute, Australia said We are facing a global epidemic of diabetes. The ADVANCE results go beyond existing evidence as we have now shown that reducing the haemogloboin A1c level (a marker of blood glucose control) to 6.5% is a safe and effective way to reduce serious complications, particularly the risk of kidney disease, one of the most serious and disabling consequences of diabetes, leading to death in one in five people with diabetes.

Hypoglycemia (low blood sugar) was uncommon in the ADVANCE study, although as expected it was more frequent among those receiving intensive treatment, pointed out Study Director, Associate Professor Anushka Patel from The George Institute. These findings reinforce that blood glucose lowering in diabetes is safe and has an important role to play in the prevention of serious complications.

David Jayne, who took part in the study was diagnosed with type 2 diabetes eight years ago. The news that I had diabetes came as quite a shock. I decided to take part in the trial, as I wanted to give something back, having received a lot of special treatment whilst in hospital, said David. My glucose levels are well and truly under control, I do feel a lot better than I did before and I'm really enjoying life, he added

ADVANCE was initiated and designed by physicians at Australia's George Institute for International Health and involved a group of independent medical researchers from 20 countries worldwide. The study involved 11,140 patients with type 2 diabetes who were treated and followed up for five years. The study aimed to reduce levels of haemogloboin A1c to 6.5% or below. Intensive treatment included the sulfonylurea, modified-release gliclazide, for all patients and other drugs as required to achieve the haemoglobin target.

The major findings of ADVANCE show that intensive blood glucose lowering treatment:

New guidelines for treating resistant hypertension

Fri, 06 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) BIRMINGHAM, Ala. -- Resistant hypertension, blood pressure that remains above goal despite taking three antihypertensive medications or high blood pressure that is controlled but requires four or more medications to do so, may benefit from specialized diagnostic and therapeutic treatment by health care providers according to guidelines issued by the American Heart Association and co-authored by UAB physicians.

Lead author David A. Calhoun, M.D., professor of medicine in the UAB Division of Cardiovascular Disease, and colleagues said successfully treating resistant hypertension requires patients to modify lifestyle factors that contribute to treatment resistance, including using less salt, losing weight and drinking less alcohol. It also requires physicians to better diagnose and treat secondary causes of high blood pressure and more effectively use multiple-drug treatments. This is the first consensus statement to define resistant hypertension and recommend an approach for evaluation and treatment.

Calhoun said while it is not known how many people in the U.S. with high blood pressure have resistant hypertension clinical trials suggest it may as high as 20 to 30 percent.

Older age and obesity are two of the strongest risk factors associated with resistant hypertension and unfortunately, with an aging and increasing heavy population, we can anticipate resistant hypertension becoming more and more common, he said. And people need to recognize the importance of blood pressure control. Persons with resistant hypertension are at increased risk for cardiovascular diseases, including heart attacks and strokes.

Calhoun and colleagues emphasize in the statement that effective use of diuretics is essential for treatment of resistant hypertension. Calhoun said they recommend that a long-acting diuretic be part of the treatment regimen of all patients with resistant hypertension in order reduce fluid retention and thereby blood pressure. He added that some patients may also benefit from adding mineralocorticoid receptor antagonists (MRAs) to their treatment regimens. MRAs have traditionally been used to treat a condition called primary aldosteronism, which is found in about 20 percent of patients with resistant hypertension. However, recent clinical studies indicate that MRAs may be useful in treating resistant hypertension even in the absence of demonstrable aldosterone excess.

The benefit of MRAs for treating resistant hypertension has been recently appreciated, he said. Hypertension specialists are using them more commonly, but they are probably not being routinely used by other physicians. Prescription of MRAs does require biochemical monitoring, particularly measurement of serum potassium levels, which does limit there use.

Calhoun said it is important to note that uncontrolled high blood pressure and resistant hypertension are not the same and effectively evaluating a patient to distinguish between the two possibilities is key to successful treatment.

High blood pressure readings can be caused by poor medication adherence, which is not the same as resistant hypertension, he said. Confirming treatment resistance is the first step in evaluating difficult-to-treat high blood pressure. It also is important to evaluate the condition correctly because often, patients with resistant hypertension have other medical conditions that complicate their blood pressure management. If a secondary cause of hypertension is identified such as obstructive sleep apnea, renal parenchymal disease, primary aldosteronism or renal artery stenosis, treating these disorders, which may require referral to a specialist, can improve blood pressure control.

Moores UCSD Cancer Center study links vitamin D, type 1 diabetes

Thu, 05 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Sun exposure and vitamin D levels may play a strong role in risk of type 1 diabetes in children, according to new findings by researchers at the Moores Cancer Center at University of California, San Diego (UCSD) and the Department of Family and Preventive Medicine. This association comes on the heels of similar research findings by this same group regarding vitamin D levels and several major cancers.

In this new study, the researchers found that populations living at or near the equator, where there is abundant sunshine (and ultraviolet B irradiance) have low incidence rates of type 1 diabetes. Conversely, populations at higher latitudes, where available sunlight is scarcer, have higher incidence rates. These findings add new support to the concept of a role of vitamin D in reducing risk of this disease.

Ultraviolet B (UVB) exposure triggers photosynthesis of vitamin D3 in the skin. This form of vitamin D also is available through diet and supplements.

This is the first study, to our knowledge, to show that higher serum levels of vitamin D are associated with reduced incidence rates of type 1 diabetes worldwide, said Cedric F. Garland, Dr. P.H., professor of Family and Preventive Medicine in the UCSD School of Medicine, and member of the Moores UCSD Cancer Center.

The study is published June 5 in the online version of the scientific journal Diabetologia.

Type 1 diabetes is the second most common chronic disease in children, second only to asthma. Every day, 1.5 million Americans deal with type 1 diabetes and its complications. About 15,000 new cases are diagnosed in the United States each year, where this disease is the main cause of blindness in young and middle-aged adults and is among the top reasons for kidney failure and transplants in youth and midlife.

This research suggests that childhood type 1 diabetes may be preventable with a modest intake of vitamin D3 (1000 IU/day) for children, ideally with 5 to 10 minutes of sunlight around noontime, when good weather allows, said Garland. Infants less than a year old should not be given more than 400 IU per day without consulting a doctor. Hats and dark glasses are a good idea to wear when in the sun at any age, and can be used if the child will tolerate them.

The association of UVB irradiance to incidence of type 1 diabetes remained strong even after the researchers accounted for per capita healthcare expenditure. This was an important consideration because regions located near the equator tend to have lower per capita healthcare expenditures, which could result in under-reporting of type 1 diabetes.

The researchers created a graph with a vertical axis for diabetes incidence rates, and a horizontal axis for latitude. The latitudes range from -60 for the southern hemisphere, to zero for the equator, to +70 for the northern hemisphere. They then plotted incidence rates for 51 regions according to latitude. The resulting chart was a parabolic curve that looks like a smile.

In the paper the researchers call for public health action to address widespread vitamin D inadequacy in U.S. children.

This study presents strong epidemiological evidence to suggest that we may be able to prevent new cases of type 1 diabetes, said Garland. By preventing this disease, we would prevent its many devastating consequences.

International Diabetes Federation grant supports study to prevent type 2 diabetes in India

Fri, 30 May 2008 03:59:37 PST

( from http://www.rxpgnews.com ) - The International Diabetes Federation (IDF) BRIDGES translational research grant programme will fund a lifestyle intervention trial that seeks to reduce the risk of for people developing type 2 diabetes in Chennai, India.

The community based diabetes prevention programme will determine optimal ways to translate the programs developed for research studies of lifestyle interventions for diabetes prevention to real-life settings in Chennai (formerly Madras) India. The Rollins School of Public Health at Emory University will collaborate with a team of investigators from Madras Diabetes Research Foundation (MDRF) and will facilitate a study of 700 people with pre-diabetes in Chennai. The study is designed to explore ways to identify and evaluate culturally appropriate, low-cost, feasible and sustainable ways to promote changes in health behaviours, improved diet, weight loss and increased physical activity to prevent diabetes in those in South India.

The messages will be tailored to the unique dietary patterns and physical activity programmes of Indian communities and will be designed to determine if these targeted interventions are effective and cost-effective.

This grant will help researchers and clinicians to better understand how to create and deliver culturally tailored programs for the prevention of diabetes in high-risk populations. The project is designed to produce a permanent, community-based program for promoting diabetes prevention and healthy lifestyle changes said Dr. K.M. Venkat Narayan, principal investigator of the study and a world leader in translational research.

The International Diabetes Federation's Diabetes Atlas reports that India has the highest number of people with diabetes in the world. Currently, 40.9 million Indians have diabetes and by 2025, this number will rocket to 69.9 million. In addition, 35 million Indians are at risk for diabetes -impaired glucose tolerance (IGT). India is not alone in facing the diabetes epidemic. Over 250 million people worldwide live with diabetes and by 2025, over 380 million people will have the disease. (1)

All South Asians, including those with diabetes, could benefit from making the positive changes in diet, activity, and behaviour that are taught in this program, said Dr. Narayan.

Data and results from the trial will be used to design and advocate policy and public health recommendations, which will result in broader diabetes prevention efforts in India and other South Asian countries.

India is at the epicentre of the diabetes pandemic. Every effort must be taken to prevent the devastating human, social and economic effects of diabetes, said Dr. Linda Siminerio, Chair of the IDF BRIDGES Review Committee. The Chennai trial led by Dr. Narayan and Indian investigators will help to address the major public health issue

The Federation, through BRIDGES, is committed to converting research findings into useful practices for the provision of quality care and services delivered by healthcare providers. The culturally specific randomized trial in India, along with the 10 other selected translational research projects, was chosen because of its innovative idea, demonstration of the potential for health care cost savings, sustainability plans and the opportunity for its results to be widely replicated in other settings.

Suspected cause of type 1 diabetes caught 'red-handed' for the first time

Fri, 09 May 2008 03:59:37 PST

( from http://www.rxpgnews.com ) May 8, 2008 -- Scientists at Washington University School of Medicine in St. Louis working with diabetic mice have examined in unprecedented detail the immune cells long thought to be responsible for type 1 diabetes.

Researchers were able to examine the immune cells from isolated insulin-making structures in the pancreas known as the islets of Langerhans. They caught the immune cells, known as dendritic cells, red-handed: carrying insulin and fragments of insulin-producing cells known as beta cells. This can be the first step toward starting a misdirected immune system attack that destroys the beta cells, preventing the body from making insulin and causing type 1 diabetes.

The results, reported online in The Proceedings of the National Academy of Sciences, push scientists a step closer to finding ways to treat this condition.

Now that we've isolated dendritic cells from the pancreas, we can look at why they get into the pancreas and determine which of the materials that they pick up are most critical to causing this form of diabetes, says senior author Emil R. Unanue, M.D., the Paul and Ellen Lacy Professor of Pathology. That may allow us to find ways to inhibit dendritic cell function in order to block the disorder.

The American Diabetes Association estimates that 1 million to 2 million Americans suffer from type 1 diabetes, which is also called juvenile diabetes because it frequently develops in children.

Patients require insulin injections to survive because the immune system has destroyed the islets of Langerhans, which contain the body's only beta cells. The insulin these cells make is required for the critical task of regulating blood sugar levels.

Scientists detected dendritic cells in the islets years ago. Dendritic and other antigen-presenting cells are the sentinels of the immune system: They pick up bits of protein from around the body and present them to lymphocytes to initiate an immune system reaction. The lymphocytes lead immune attacks against foreign invaders like bacteria and viruses and eliminate them, clearing infections. But when interaction between an antigen-presenting cell and a lymphocyte leads to a part of the body being mistakenly identified as alien, the resulting attack harms the body, causing autoimmune diseases.

Although dendritic cells' presence in the islets and their ability to summon immune attacks made them likely suspects in type 1 diabetes, they were challenging to isolate from the pancreas for closer examination.

They're very tiny and there are only about 5 to 10 of them per islet, each of which contains approximately a thousand cells, explains Unanue. So the senior postdoctoral researcher in the lab who did this work, Boris Calderon, had to develop some sophisticated cellular assays to pick them up.

Calderon, M.D., found indications that the cells were carrying granules of insulin and pieces of proteins from beta cells on their cell surfaces. To test whether this cargo carried by the dendritic cells had the potential to trigger an immune attack on beta cells, Calderon exposed the dendritic cells to lymphocytes taken from diabetic mice. The lymphocytes were activated by the dendritic cells of the islets and switched into attack mode.

In a separate line of research, Unanue's lab has learned that dendritic cells in the pancreas may normally have beneficial effects on the health of beta cells. They've shown that when dendritic cells are absent from the pancreas, the beta cells are smaller, an indication that they're not as healthy.

We think these dendritic cells aren't in the pancreas by accident, says Unanue. We believe that in the normal individual they help maintain the health of beta cells. But in a person with autoimmune diabetes, they appear to start the problems that destroy beta cells.

The key distinction likely lies in a group of proteins called the major histocompatibility complex (MHC). Two decades ago, Unanue and Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, showed that the MHC provides the stage on which antigen-presenting cells show bits of protein or peptides to other immune system cells. Scientists believe autoimmune conditions like type 1 diabetes are caused by differences in what the MHC binds to and how it presents that material to immune attack cells. In support of this theory, Unanue's laboratory and that of Michael Gross, Ph.D., Washington University professor of chemistry, have collaboratively shown that the genes that encode the MHC proteins in the diabetic mouse are unique and bind to a set of very characteristic peptides.

In addition to studying what protein fragments carried by dendritic cells are essential for causing type 1 diabetes, Unanue and others are working to learn how genetic variations in the MHC alter the chances that the immune system will mistakenly attack the body.

Harmful blood glucose levels linked to defective gene

Thu, 01 May 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A genetic mutation that can raise the amount of glucose in a person's blood to harmful levels is identified today in a study in the journal Science.

High levels of blood glucose increase the risk of cardiovascular disease and early death, even in healthy people who do not have diabetes and whose blood glucose levels are at the higher end of the range considered 'normal' by doctors. One in five people in the UK has a high blood glucose level.

The study, by researchers from Imperial College London, the French National Research Institute and McGill University in Canada, reveals an association between high levels of blood glucose and a mutation in a gene known as G6PC2 or IGRP.

The research shows that the mutated IGRP gene blocks the action of a sensor called glucokinase. By stopping glucokinase from doing its job, the gene prevents the body from keeping tight control over its levels of blood glucose. Glucokinase works by signalling to cells known as beta cells which then secrete insulin to keep blood glucose levels under control.

The researchers hope their findings could enable a therapy to be developed to stop the defective IGRP gene from blocking the glucokinase sensor. This would restore control of glucose levels in the blood and help prevent these levels from becoming too high.

The researchers believe that the mutation in the IGRP gene could cause an increase of around five percent in the level of glucose in the blood. This small percentage increase would be enough to raise a person's risk of health problems because levels of blood glucose are so tightly controlled.

Epidemiological studies have shown that 80 percent of the risk of cardiovascular disease is related to a blood glucose level just above the average. High blood glucose levels are linked to obesity, poor nutrition and lack of exercise.

Professor Philippe Froguel, leading author of the research from the French National Research Institute and the Department of Genomic Medicine at Imperial College London, said: Having a high level of blood glucose is a bit like having high cholesterol or high blood pressure in that the higher the level, the greater your risk of serious health problems. Our study helps unravel the genetic reasons why some people have higher levels of glucose in their blood than others.

At present, doctors advise people with high blood glucose levels to lose weight and exercise. We hope that ultimately our research will mean we can develop new treatments to stop people from developing high blood glucose levels, which would enable them to live longer and healthier lives, added Professor Froguel.

The scientists reached their conclusions after comparing the genetic makeup of 654 non diabetic people with differing levels of blood glucose, from the low to the high end of the 'normal' range. The researchers looked at mutations in the building blocks, called nucleotides, which make up DNA.

There are mutations, known as single-nucleotide polymorphisms, in around one in every 600 nucleotides. The scientists examined over 392,000 of these mutations to find the ones specific to high blood glucose levels. The researchers confirmed their findings by analysing the genetic makeup of a further 8000 individuals with blood glucose levels within the non diabetic range, to verify that the same genetic mutations were visible in these individuals.

Today's study follows on from a study published in February 2007 by the same team, where they identified the most important genes associated with a risk of developing type-2 diabetes.

Researchers uncover new genetic links to psoriasis

Thu, 03 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) In the first comprehensive study of the genetic basis of psoriasis, researchers at Washington University School of Medicine in St. Louis have discovered seven new sites of common DNA variation that increase the risk of the troublesome skin condition. They also found that variations in one genetic region link psoriasis and a related joint disorder, psoriatic arthritis, to four autoimmune diseases: type 1 diabetes, Grave's disease, celiac disease and rheumatoid arthritis.

The study's results appear April 4 in the open-access journal PLoS Genetics.

Common diseases like psoriasis are incredibly complex at the genetic level, says lead investigator Anne Bowcock, Ph.D., professor of genetics at the School of Medicine. Our research shows that small but common DNA differences are important in the development of psoriasis. Although each variation makes only a small contribution to the disease, patients usually have a number of different genetic variations that increases their risk of psoriasis and psoriatic arthritis.

The DNA variations uncovered by the researchers point to different biological pathways that underlie psoriasis and may eventually lead to new targeted drugs and treatments that hit specific pathways, Bowcock says.

An estimated 7 million Americans have psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin. The condition is characterized by red, scaly patches that can be itchy, painful or both. Some 10 to 30 percent of patients with psoriasis develop psoriatic arthritis, a condition that is often excruciatingly painful and debilitating.

The Washington University researchers focused on points of common variation in the genome called single nucleotide polymorphisms, or SNPs. While most of the 3 billion nucleotides that comprise DNA are thought to be identical from one person to the next, some 10 million SNPs build variation into the genome and make each individual unique. Some of these SNPs play a crucial role in a person's predisposition to disease or good health.

Using an approach known as whole genome association, the investigators scanned more than 300,000 SNPs in the genomes of 223 psoriasis patients, including 91 who had psoriatic arthritis. They compared the DNA variations in people with psoriasis to those found in 519 healthy control patients, looking for specific differences that may be linked to the disease. They then replicated their findings in a larger set of patients -- 577 with psoriasis and 576 with psoriatic arthritis -- and more than 1,200 healthy controls.

Bowcock and her team found seven novel DNA variations linked to psoriasis. Four other variations associated with the disease that had been identified previously by other researchers also were confirmed by the current study.

Whole genome association studies have recently been used to identify common genetic variations that increase the risk of diseases such as breast cancer, heart disease and type 2 diabetes. They typically involve more than 1,000 patients with a particular disease to help ensure that the genetic variations identified in the study do not occur by chance. While the current study included fewer patients, nearly half of them had a sibling and, in some cases, a parent with psoriasis, which increases the odds of finding genetic variations that contribute to the disease.

The researchers found the strongest genetic risk for psoriasis lies in a region of the genome that contains the major histocompatibility complex, a collection of genes involved in distinguishing the body's own cells from foreign invaders. Although this region has been known to play a major role in psoriasis, DNA variations in the MHC alone have been known to not be enough to trigger disease, Bowcock says. Only 10 percent of patients with variations in the major histocompatibility complex developed psoriasis. This tells us that other genetic or environmental factors also contribute to the disease.

One MHC variation linked to psoriasis and psoriatic arthritis occurs in the gene HCP5, the scientists noted. That variation was recently reported to delay the onset of AIDS in people infected with HIV. This is particularly interesting, Bowcock says, because psoriasis can be triggered by infection with HIV or other viruses. It may be that in people with this SNP variant, viral infection triggers a larger immune response that slows the development of AIDS but also leads to excessive inflammation in the skin and bone joints in genetically susceptible individuals, leading to the onset of psoriasis and psoriatic arthritis.

Notably, DNA variations on chromosome 4 were strongly linked to psoriatic arthritis. These same variations were also associated with psoriasis and had been previously linked to type 1 diabetes, rheumatoid arthritis, Grave's disease (caused by an overproductive thyroid gland) and celiac disease (caused by the inability to digest gluten). Doctors have noticed that some psoriasis patients have autoimmune diseases such as celiac disease, Grave's disease, and type 1 diabetes, Bowcock says. But we didn't know whether this was a coincidence. Now we know there is a genetic component underlying all of these diseases.

The same region of chromosome 4 contains genes that code for the signaling molecules IL2 and IL21. This opens the door to investigating whether existing drugs that block either molecule may be effective in some psoriasis patients, especially those with psoriatic arthritis.

The researchers also uncovered significant DNA variations on chromosome 13 in a genetic region involved in modifying proteins, and on chromosome 15, in a region responsible for producing a protein that activates TNF alpha (tumor necrosis factor-alpha) in a specialized immune cell known as a dendritic cell. While TNF alpha normally helps fight infections, it is thought to be a major player in psoriasis and psoriatic arthritis. Several FDA-approved psoriasis medications work by binding to TNF-alpha, thereby preventing it from communicating with cells.

Bowcock is now involved in a larger genome-wide association study of psoriasis patients and says she expects it will uncover additional genetic variations that are associated with psoriasis.

Eventually, she predicts, such studies will lead to more effective, better-targeted therapies.

The goal of this study and other genome-association studies is to get to personalized medicine, where you can diagnose a disease and ask what genetic risk factors this person has that points to altered pathways, she says. Then, we can target those pathways for specific therapeutic interventions.

How diabetes accelerates atherosclerosis

Thu, 13 Mar 2008 10:11:37 PST

( from http://www.rxpgnews.com ) Researchers have discovered how diabetes, by driving inflammation and slowing blood flow, dramatically accelerates atherosclerosis, according to research to be published in the March 14 edition of the journal Circulation Research.

Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body's immune system to fatty build-up, more than the build-up itself, creates heart attack risk. Immune cells traveling with the blood mistake fatty deposits for intruders, akin to bacteria, home in on them, and attack. This causes inflammation that makes plaques more likely to swell, rupture and cut off blood flow.

Making matters worse, nearly 21 million Americans have diabetes, a disease where patients’ cells cannot efficiently take in dietary sugar, causing it to build up in the blood. In part because diabetes increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke.

Past work has shown that high blood sugar has two effects on cells lining blood vessels as part of atheroslerosis. First, it increases the production of free radicals, highly reactive molecules that tear about sensitive cell components like DNA, causing premature cell death (apoptosis). This process also reduces the availability of nitric oxide (NO), which would otherwise enable blood vessels to relax and blood flow to increase. In contrast to diabetes, exercise and good diet bring about faster blood flow through blood vessels. The force created by fast, steady blood flow as it drags along blood vessel walls has been shown by recent studies to protect arteries from atherosclerosis. Physical force has emerged recently as a key player in bodily function, capable of kicking off biochemical processes (e.g. weightlifting thickens bone).

“Inflammation is blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse,” said Jun-ichi Abe, M.D., Ph.D., associate professor with the Aab Cardiovascular Research Center at the University of Rochester Medical Center, and a study author. “Our study argues that a pathway surrounding a key signaling enzyme both protects the heart in normal cases, and is sabotaged by the chemicals produced in diabetes. We believe we have found a new therapeutic target for the treatment of diabetes-related damage to blood vessels.”

How Diabetes Does It

In people without diabetes, fast blood flow triggers an enzyme called extracellular signal-regulated kinase 5 (ERK-5). ERK5 in turn signals endothelial nitric oxide synthase (eNOS) to produce more nitric oxide and dilate blood vessels. It also activates Kruppel-like factor 2 (KLF2) and peroxisome proliferator-activated receptor-g (PPARg), both of which block the ability of pro-inflammatory immune cells to home in on and adhere to diseased portions of blood vessels.

Past studies had shown diabetes to worsen atherosclerosis, but its exact link to related inflammation had remained unclear. The current results provides the first mechanistic description of how diabetes takes away the ability of fast blood flow force to protect blood vessels, arguing that it does so by interfering with ERK5 and its signaling partners.

Abe’s team showed that molecules called advanced glycation end products (AGEs), produced in greater levels by patients with diabetes, interfere with ERK5 cardioprotection. Glycation reactions cause the release of oxidizing side products like hydrogen peroxide (H202) that drive free radical production, inflammation and cell damage in many diseases.

Researchers found that AGEs and H202 sabotage ERK5 by encouraging the attachment to it of a small ubiquitin-related modifier (SUMO), a protein tag used by cells to fine-tune their control over proteins. In normal function, a cell may extend a protein’s lifespan, or send it from one part of the cell to another, by attaching a SUMO tag. In the current study, researchers found that AGEs and H202 induced ERK5-SUMOylation as part of disease. In addition, the team found that ERK5-SUMOylation was increased in the aortas of diabetic mice.

Along with Abe, Chang-Hoon Woo, Tetsuro Shishido and Carolyn McClain contributed to the work within the Aab Cardiovascular Research Center. Jae Hyang Lim and Jian-Dong Li within the Department of Microbiology & Immunology at the Medical Center contributed expertise, along with Jay Yang, professor of Anesthesiology at Columbia University. This work is supported by grants from the America Heart Association and the National Institutes of Health.

“Our experiments found that taking away the “SUMO tag” from ERK protects blood vessels against diabetes,” Abe said. “We believe that the SUMOylation of ERK turns off ‘good’ genes that are important in countering atherosclerosis. In the next phase, we will be looking for drug candidates that can turn on ERK5 as diabetes attempts to shut it down.”

CRTC2 inhibitors may be needed for maintaining sugar levels

Sun, 09 Mar 2008 06:57:00 PST

( from http://www.rxpgnews.com ) Continually revved up insulin production, the kind that results from overeating and obesity, slowly dulls the body’s response to insulin. As a result, blood sugar levels start to creep up, setting the stage for diabetes-associated complications such as blindness, stroke and renal failure. To make matters even worse, chronically elevated blood sugar concentrations exacerbate insulin resistance.

The vicious circle gets rolling, researchers at the Salk Institute for Biological Studies discovered, when out-of-control blood sugar levels disable the molecular switch that normally shuts off sugar production in the liver in response to rising levels of insulin.

Their findings, published in the March 7 issue of Science suggest that appropriate inhibitors of the enzymatic pathway that blocks the “sugar-off”-switch might be useful in lowering glucose levels in diabetic individuals and reducing long-term complications associated with the disease.

“The islet cells in the pancreas can compensate with increased insulin production only for so long when confronted with chronic obesity and inactivity,” says Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. “As a result glucose levels start to rise causing a host of problems.”

Just like a flex-fuel vehicle that can run on either gasoline or ethanol, the human body can switch between different types of fuel: During the day the body mostly burns glucose, and during the night or prolonged fasting, it burns primarily fat. But neither flex-fuel engines nor human brains can run on ethanol or fat alone —a little bit of gasoline or glucose needs to be thrown into the mix to keep either one of them humming.

Three years ago, Montminy discovered a “fasting switch” called CRTC2 (formerly known as TORC2) that flips on glucose production in the liver when blood glucose levels run low during the night. After a meal, the hormone insulin normally shuts down CRTC2 ensuring that blood sugar levels don’t rise too high.

In many patients with type II diabetes, however, CRTC2 no longer responds to rising insulin levels and as a result the liver acts like a sugar factory on overtime, churning out glucose throughout the day, even when blood sugar levels are high. The Salk researchers were interested in the molecular mechanism that leads to the breakdown of the normally tightly regulated feedback loop.

Mice whose livers light up — courtesy of the luciferase gene, which produces the glow in fireflies — as soon as CRTC2 is turned on, led post-doctoral fellow and first author Renaud Dentin, Ph.D., onto the trail of the hexosamine biosynthetic pathway. Activation of the pathway promotes the addition of sugar molecules to proteins, a process also known as O-glycosylation. “It had been known that increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway,” says Dentin. “But we had no idea that the resulting O-glycosylation would lock CRTC2 in the ‘on’-position.”

Normally, the rise in insulin after a meal activates a liver enzyme called SIK2. The enzyme chemically tags CRTC2 with a phosphate group, marooning the protein outside the cell’s nucleus. Unable to reach the genes involved in gluconeogenesis, CRTC2 is powerless to turn them on and glucose production in the liver ceases.

In the presence of excessive glucose levels, however, the hexosamine biosynthetic pathway is activated and blocks crucial phosporylation sites on CRTC2 by adding sugar molecules instead. CRTC2 can no longer be phosphorylated in response to rising insulin levels and is now free to slip into the nucleus and keep the gluconeogenic program going.

Shutting down the O-glycosylation pathway should then get the body’s own glucose production under control, the researchers reasoned. Just as predicted, glucose tolerance and insulin sensitivity markedly improved in insulin resistant diabetic mice and mice fed a high fat diet — who both suffered from hyperglycemia — when Dentin and his colleagues decreased the activity of the hexosamine biosynthetic pathway in the liver of these animals.

“What I really would like to do is to use the glowing mice to screen for drugs that decrease gluconeogenesis,” says Montminy. “Imagine hyperglycemic mice whose livers light up because CRTC2 is on all the time. When you feed them a drug that inhibits O-glycosylation the light dims and you know you have compound that’s effective in living animals and you know how it works.”

A focus on the ADVANCE and RISC studies in the Diabetes UK conference March 2008

Sat, 08 Mar 2008 07:21:44 PST

( from http://www.rxpgnews.com ) In the recent Annual Professional Conference held in Glasgow(March 5-7, 2008) an interesting talk was on the late breaking trials. There was a focus on the ADVANCE study (presented by Dr Neil Poulter, London) and the RISC study (presented by Dr Mark Walker, Newcastle). Here is a brief overview of the studies and the thoughts of the speakers and audience.

The Advance study which was published in The Lancet, September 2007, has sparked off a lot of discussion this year. As we know the previous UKPDS study had defined a tight systolic BP control as being <140, and this really needed another trial in keeping with recent guidelines like JSB. ADVANCE was a randomised controlled trial done across 20 countries from Asia, Australasia, Europe, and North America. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial was designed to assess the effects on vascular disease of using a fixed combination of the ACE inhibitor, perindopril, and the diuretic, indapamide, in a diverse population of patients with type 2 diabetes and a broad range of blood pressure values. The study also assesses the effects on the same outcomes of an intensive gliclazide MR-based glucose lowering regimen (aiming for a haemoglobin A1C level of 6•5% or lower) compared with standard glucose control.
INCLUSION CRITERIA-Patients were eligible if they had been diagnosed with type 2 diabetes mellitus at the age of 30 years or older and were aged 55 years or older, with a history of major cardiovascular disease or at least one other risk factor for cardiovascular disease. Patients could be normotensive or hypertensive to be included.
METHODS- Patients had an initial run –in period of 6 weeks prior to randomisation when they were given 2 mg perindopril and 0.625 mg of indapamide. Those who were on other ACE inhibitor drugs were switched to perindopril. If the patients tolerated these drugs, then after 6 weeks they were randomly assigned to combined perindopril (2 mg) and indapamide (0•625 mg) or matching placebo for 3 months. Then the doses of randomised therapy were doubled to 4 mg for perindopril and 1•25 mg for indapamide, or matching placebo.
FINDINGS-Over the duration of follow-up, blood pressure was reduced by an average of 5•6 mm Hg systolic and 2•2 mm Hg diastolic in patients assigned active treatment compared to the control. The relative risk reduction for combined macrovascular and microvascular events was 9% in the treated group compared to the placebo group, and similarly the reduction in the macrovascular events risk was 8% and that in the microvascular events was 9%.
DISCUSSION- What was considered significant was the fact that the study failed to show any reduction in the endpoints of stroke and in microvascular eye disease. The stroke rate was thought to be the same in both groups due to the use of calcium channel blockers in the control group. It was put forward as the speaker’s thoughts that the reduction in events may have been due to the Blood pressure lowering, due to the drugs used or due to the RAS blockage via the ACE inhibitors. The recent stoppage of the intensive blood sugar treatment arm in the ACCORD study which was stopped due to increased mortality was also discussed and it was felt that maybe the higher insulin usage and the higher risk population in the ACCORD study may have contributed to those adverse events.

The Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study was presented by Mark Walker, Newcastle University, UK. The study was a multicentric, prospective cohort study to establish whether insulin resistance predicts development of cardiovascular disease, to determine genetic and environmental contributions and to develop a method of identifying insulin resistant subjects in clinical practice.
INCLUSION – Patients between the ages of 30-60 years who were not known to have hypertension, diabetes mellitus, dyslipidaemia or established, cardiovascular disease, renal failure, cancer or lung disease.
METHOD – Insulin resistance was measured with a hyperinsulinaemic, euglycaemic clamp. Physical examination, CVD risk assessment, oral glucose tolerance test, measurement of physical activity with an accelerometer and measurement of carotid artery intima media thickness measurement was carried out. There is an initial 3 year and then 10 year follow up.
RESULTS- It was found that the BMI, waist – hip ratio, insulin resistance and insulin exposure independently predicted Cardiometabolic risk factor score. Insulin sensitivity was found to increase with level of activity. Total physical activity was also associated with carotid artery stiffness. The CDKAL and HHEX/IDE susceptibility alleles were associated with impaired pancreatic ß cell function. Only the FTO allele was associated with decreased insulin sensitivity, which was mediated through increased adiposity. Longitudinal data over the complete planned follow-up period is needed to show whether insulin resistance is an independent predictor of the development of atherosclerosis and CVD.

Type 2 diabetes may be caused by intestinal dysfunction

Wed, 05 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (March 5, 2008) -- Growing evidence shows that surgery may effectively cure Type 2 diabetes -- an approach that not only may change the way the disease is treated, but that introduces a new way of thinking about diabetes.

A new article -- published in a special supplement to the February issue of Diabetes Care by a leading expert in the emerging field of diabetes surgery -- points to the small bowel as the possible site of critical mechanisms for the development of diabetes.

The study's author, Dr. Francesco Rubino of NewYork-Presbyterian Hospital/Weill Cornell Medical Center, presents scientific evidence on the mechanisms of diabetes control after surgery. Clinical studies have shown that procedures that simply restrict the stomach's size (i.e., gastric banding) improve diabetes only by inducing massive weight loss. By studying diabetes in animals, Dr. Rubino was the first to provide scientific evidence that gastrointestinal bypass operations involving rerouting the gastrointestinal tract (i.e., gastric bypass) can cause diabetes remission independently of any weight loss, and even in subjects that are not obese.

By answering the question of how diabetes surgery works, we may be answering the question of how diabetes itself works, says Dr. Rubino, who is a professor in the Department of Surgery at Weill Cornell Medical College and chief of gastrointestinal metabolic surgery at NewYork-Presbyterian/Weill Cornell.

Dr. Rubino's prior research has shown that the primary mechanisms by which gastrointestinal bypass procedures control diabetes specifically rely on the bypass of the upper small intestine -- the duodenum and jejunum. This is a key finding that may point to the origins of diabetes.

When we bypass the duodenum and jejunum, we are bypassing what may be the source of the problem, says Dr. Rubino, who is heading up NewYork-Presbyterian/Weill Cornell's Diabetes Surgery Center.

In fact, it has become increasingly evident that the gastrointestinal tract plays an important role in energy regulation, and that many gut hormones are involved in the regulation of sugar metabolism. It should not surprise anyone that surgically altering the bowel's anatomy affects the mechanisms that regulate blood sugar levels, eventually influencing diabetes, Dr. Rubino says.

While other gastrointestinal operations may cure diabetes as an effect of changes that improve blood sugar levels, Dr. Rubino's research findings in animals show that procedures based on a bypass of the upper intestine may work instead by reversing abnormalities of blood glucose regulation.

In fact, bypass of the upper small intestine does not improve the ability of the body to regulate blood sugar levels. When performed in subjects who are not diabetic, the bypass of the upper intestine may even impair the mechanisms that regulate blood levels of glucose, says Dr. Rubino. In striking contrast, when nutrients' passage is diverted from the upper intestine of diabetic patients, diabetes resolves.

This, he explains, implies that the upper intestine of diabetic patients may be the site where an abnormal signal is produced, causing, or at least favoring, the development of the disease.

How exactly the upper intestine is dysfunctional remains to be seen. Dr. Rubino proposes an original explanation known in the scientific community as the anti-incretin theory.

Incretins are gastrointestinal hormones, produced in response to the transit of nutrients, that boost insulin production. Because an excess of insulin can determine hypoglycemia (extremely low levels of blood sugar) -- a life-threatening condition -- Dr. Rubino speculates that the body has a counter-regulatory mechanism (or anti-incretin mechanism), activated by the same passage of nutrients through the upper intestine. The latter mechanism would act to decrease both the secretion and the action of insulin.

In healthy patients, a correct balance between incretin and anti-incretin factors maintains normal excursions of sugar levels in the bloodstream, he explains. In some individuals, the duodenum and jejunum may be producing too much of this anti-incretin, thereby reducing insulin secretion and blocking the action of insulin, ultimately resulting in Type 2 diabetes.

Indeed, in Type 2 diabetes, cells are resistant to the action of insulin (insulin resistance), while the pancreas is unable to produce enough insulin to overcome the resistance.

After gastrointestinal bypass procedures, the exclusion of the upper small intestine from the transit of nutrients may offset the abnormal production of anti-incretin, thereby resulting in remission of diabetes.

In order to better understand these mechanisms, and help make the potential benefits of diabetes surgery more widely available, Dr. Rubino calls for prioritizing research in diabetes surgery. Further research on the exact molecular mechanisms of diabetes, surgical control of diabetes and the role played by the bowel in the disease may bring us closer to the cause of diabetes.

Today, most patients with diabetes are not offered a surgical option, and bariatric surgery is recommended only for those with severe obesity (a body mass index, or BMI, of greater than 35kg).

It has become clear, however, that BMI cut-offs can no longer be used to determine who is an ideal candidate for surgical treatment of diabetes, says Dr. Rubino.

There is, in fact, growing evidence that diabetes surgery can be effective even for patients who are only slightly obese or just overweight. Clinical trials in this field are therefore a priority as they allow us to compare diabetes surgery to other treatment options in the attempt to understand when the benefits of surgery outweigh its risks. Clinical guidelines for diabetes surgery will certainly be different from those for bariatric surgery, and should not be based only on BMI levels, he notes.

The lesson we have learned with diabetes surgery is that diabetes is not always a chronic and relentless disease, where the only possible treatment goal is just the control of hyperglycemia and minimization of the risk of complications. Gastrointestinal surgery offers the possibility of complete disease remission. This is a major shift in the way we consider treatment goals for diabetes. It is unprecedented in the history of the disease, adds Dr. Rubino.

Type 2 diabetes, which accounts for 90 to 95 percent of all cases of diabetes, is a growing epidemic that afflicts more than 200 million people worldwide.

At a time when diabetes is growing epidemically worldwide, Dr. Rubino says that finding new treatment strategies is a race against time. At this point, missing the opportunity that surgery offers is not an option.

Protein target for diabetes drug regulates blood pressure

Tue, 04 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) University of Iowa researchers have identified a molecular pathway in blood vessels that controls blood pressure and vascular function and may help explain why certain drugs for type II diabetes also appear to lower patients' blood pressure. The study is published in the March 5 issue of Cell Metabolism.

A majority of patients with type II diabetes, which is associated with obesity and metabolic syndrome, also are at risk for serious cardiovascular problems, including atherosclerosis, heart attack, stroke and hypertension. Understanding the biological pathways that link cardiovascular and metabolic function could lead to better treatments for the millions of Americans affected by these conditions.

The focus of the UI study is a protein called peroxisome proliferator-activated receptor gamma (PPAR gamma), which plays a critical role in fat metabolism and insulin action, and appears to link metabolic disorders, like type II diabetes, with cardiovascular disease.

Drugs called thiazolidinediones (TDZs), which are used to treat type II diabetes, target and activate PPAR gamma. In addition to controlling blood sugar, these drugs also appear to lower blood pressure.

The UI team led by Curt Sigmund, Ph.D., professor of internal medicine and molecular physiology and biophysics in the UI Roy J. and Lucille A. Carver College of Medicine, and Carmen Halabi, a student in the UI Medical Scientist Training Program and the study's lead author, tested the idea that these two beneficial effects of TZDs are produced through two separate PPAR gamma pathways.

Working with mice, the team knocked out the function of PPAR gamma in vascular smooth muscle, which surrounds blood vessels. The mice developed high blood pressure and very severe vascular dysfunction, which resembled the vascular disorders often seen in patients with advanced type II diabetes.

It appears that when PPAR gamma is activated it initiates a cascade of events that protect the blood vessel, Sigmund explained. When we interfere with the PPAR gamma pathway, those protective mechanisms are eliminated and the blood vessel becomes dysfunctional.

Although TZDs have been used for many years to treat type II diabetes, they do have several serious side effects, including weight gain and water retention. A recent study also suggested that one TZD (rosiglitazone, which is sold as Avandia) might increase the incidence of fatal and non-fatal heart attacks in diabetes patients. Avandia now carries an FDA warning.

These side effects really highlight the need to figure out ways to dissociate beneficial effects from dangerous side effects, Sigmund said. By understanding the mechanisms that lead to those effects we may be able to enhance benefits and minimize dangers.

When a drug is found to have serious side effects, people often think that the molecule the drug targets is no longer relevant, he added. But that is not the case. We know from our study and from others that the molecule is still very relevant. We just need drugs with higher specificity.

Sigmund also noted that Halabi's combined training in medicine and bench science helped to focus the genetic study on an area with direct clinical relevance.

This study is at the interface of her knowledge of clinical medicine and the basic science, he said.

PPAR gamma is a transcription factor and when it is activated, a cascade of signals is initiated, which controls gene expression -- some genes are turned on and others are turned off. In particular, inflammatory genes are turned off and antioxidant genes are turned on.

Having identified the PPAR gamma pathway, the next question for the researchers is which genes are being turned on or off to produce the antihypertensive effect Identifying these genes may lead to more specific ways of treating hypertension and vascular disease in patients with diabetes.

Study: highly involved patients don't always see better health outcomes

Fri, 22 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Patients who prefer to be highly involved in their treatment don't necessarily have better luck managing chronic health conditions, a new study suggests.

A research team based at the Veterans Affairs (VA) Iowa City Health Care System and the University of Iowa surveyed 189 veterans with high blood pressure to determine the patients' preferences for involvement in their health care. They discovered those who wanted an active role in their treatment had higher blood pressure and cholesterol over a 12-month span than those who wanted a less active role.

The study, published this week in the Annals of Behavioral Medicine, was led by Austin Baldwin, a post-doctoral fellow in the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the VA Iowa City Health Care System and an adjunct assistant professor of psychology in the UI College of Liberal Arts and Sciences.

The intuitive assumption is that the more involved people are with their health, the better they'll be at managing chronic conditions. We found evidence to the contrary, Baldwin said. Those who preferred a more 'patient-centered' or active role actually had higher blood pressure and lipid levels. Those who preferred a 'provider-centered' approach, in which the doctor is more authoritative, did better at managing their blood pressure and lipid levels.

Patients who preferred the most active role averaged a blood pressure of 141 over 79 and a low-density lipoprotein (LDL) cholesterol level of 112, while those who preferred the least active role averaged a blood pressure of 137 over 72 and an LDL of 92. Doctors tell most patients with high blood pressure to aim for a blood pressure less than 140 over 90 and keep LDL cholesterol under 130.

The average participant was 65.8 years old, and 97 percent were men. Participants were recruited from the Iowa City and Minneapolis VA health care systems and four affiliated community-based outpatient clinics as part of a larger hypertension trial. The data were collected in 2004.

The research team offered a couple potential explanations for the results.

One possibility is that patients who wanted an active role were dissatisfied with the relatively passive treatment of taking medication to control their conditions, and therefore may not have followed doctors' orders as well.

They were presumably provided advice and guidance about modifying their lifestyle, but all of these patients were on hypertension medication, and many were on lipid-lowering medications, Baldwin said. For those who want more control over their treatment, a relatively passive treatment like taking medication may not be a good match.

One aspect of the study gave traction to this explanation. Some patients were diabetic. While those who preferred an active role did worse at managing blood pressure and cholesterol, they did slightly better at managing blood sugar (although the effect on managing blood sugar was not statistically significant). Researchers believe that's because managing blood sugar is a more hands-on treatment involving blood sugar tests, diet regulation and sometimes medication.

Another potential explanation is that the patients' role preferences didn't match their doctors' role preferences. While this study did not assess providers' preferences, previous research suggests that a mismatch between patients' and providers' role preferences impacts adherence to treatment recommendations. (See related UI study at

Intensive blood sugar treatment in trial of diabetes and cardiovascular disease changed

Wed, 06 Feb 2008 23:39:37 PST

( from http://www.rxpgnews.com ) The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped one treatment within a large, ongoing North American clinical trial of diabetes and cardiovascular disease 18 months early due to safety concerns after review of available data, although the study will continue.

In this trial of adults with type 2 diabetes at especially high risk for heart attack and stroke, the medical strategy to intensively lower blood glucose (sugar) below current recommendations increased the risk of death compared with a less-intensive standard treatment strategy. Study participants receiving intensive blood glucose lowering treatment will now receive the less-intensive standard treatment.

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants. Of these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment group. This is a difference of 54 deaths, or 3 per 1,000 participants each year, over an average of almost four years of treatment. The death rates in both groups were lower than seen in similar populations in other studies.

Insulin inhibits resistin expression and secretion

Wed, 16 Jan 2008 14:07:06 PST

( from http://www.rxpgnews.com ) Obesity is a worldwide health problem directly linked to several diseases such as hypertension and type 2 diabetes. Resistin is a cysteine-rich hormone mainly secreted by adipose tissues and may form a biochemical link between obesity and type 2 diabetes.

It has been reported insulin inhibits resistin mRNA level in 3T3-L1, which does not support a role for resistin in insulin resistance. Does resistin play a role in insulin resistance? Is insulin the major regulator of resistin?

A research article to be published on January 7, 2008 in the World Journal of Gastroenterology (volume 14, issue 1) addresses these questions. The research team led by Dr. Guo Xi-Rong studied the resistin action in vitro and resistin secretion. In addition to this, diet-induced obese rats were used to study the relationship between insulin, resistin and insulin resistance.

One result reported by the investigators was resistin expression and secretion was enhanced during 3T3-L1 pre-adipocytes differentiation, insulin inhibits resistin expression and secretion. Insulin does not support a role for resistin in insulin resistance.

The result showed resistin induces cellular insulin resistance in H4IIE hepatocytes and L6 rat myoblasts. Serum resistin negatively correlates to insulin sensitivity, not to serum insulin in diet-induced obesity rats.

The results of this study suggest insulin inhibits resistin secretion and resistin induces insulin sensitivity. In vivo study shows serum resistin correlated to rat insulin sensitivity, so insulin is not the major regulator of resistin. Resistin induced hepatocytes insulin resistance takes part in diet induced insulin resistance.

Oral anti diabetic substance discovered

Mon, 24 Dec 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Research in the Department of Biology at the Faculty of Science and Science Education of the University of Haifa has discovered a substance that may become an oral treatment for diabetes and its complications. The substance, which is derived from yeast, is called Glucose Tolerance Factor (GTF). The research is now at the stage where the substance has been successfully tested on diabetic rats and was found to reduce sugar and lipids in the blood of the treated animals. The next stage of the research is to evaluate GTF efficacy in humans, said Dr. Nitsa Mirsky, who is conducting the research.

Diabetes is recognized as a major global health problem. Diabetes affects 5%-10% of the population in developed countries, while in developing countries the disease has been recently declared an epidemic. Diabetics suffer from lack of insulin or a deficiency in the body's ability to respond to insulin. Diabetes is a chronic illness with no cure and can lead to kidney failure, heart problems, strokes or blindness, as well as other complications. Approximately 50% of diabetics are treated with insulin, which has to be injected, while the rest are treated with oral medications which tend to be more difficult to regulate and often have side effects.

According to Dr. Mirsky, there are a number of problems with insulin treatment; the main one being that insulin is not always an effective treatment, due to gradual development of resistance to the hormone. An additional problem is that insulin doses are not necessarily synchronized with the patient's physical activities or eating intervals. A large dose of insulin injected before a diabetic patient eats, for example, can cause a sudden drop in blood sugar (hypoglycemia) that can result in a diabetic coma and ultimately death. In addition, the fact that insulin must be injected is in and of itself difficult for many patients.

This current research was conducted on two levels: on diabetic rats and on the molecular-cell level. The results indicate that GTF acts similarly to insulin in the rats, lowering the level of glucose, and of LDL-cholesterol, (the bad cholesterol), and raising the level of HDL-cholesterol (the good cholesterol). GTF inhibited oxidation processes that can cause atherosclerosis and result in further complications of the disease like strokes and heart attacks. Moreover, when GTF is given at early stage of the disease, it could prevent or delay renal complications. GTF also helped to prevent cataracts and retinal damage. It was also found that GTF improves the effectiveness of injected insulin. Further research is needed in order to find a combined regimen of insulin and GTF as a potential treatment for diabetes.

Stanford researchers shed light on black box of gestational diabetes

Thu, 01 Nov 2007 03:59:37 PST

( from http://www.rxpgnews.com ) STANFORD, Calif. - A protein in the pancreas is giving researchers at the Stanford University School of Medicine their first chance at cracking the code that determines how diabetes develops during pregnancy, a finding that could lead to new treatments for all forms of diabetes.

The study may help explain why roughly 5 percent of women develop diabetes temporarily while pregnant, a condition called gestational diabetes. That condition is a leading cause of birth defects and can predispose the child to develop diabetes later in life.

The basis of gestational diabetes has been a black box, said Seung Kim, MD, PhD, associate professor of developmental biology and senior author on the study. The results will be published in the Nov. 2 issue of the journal Science.

The protein Kim and his colleagues studied, called menin, was already known to have a role in preventing cancer in the pancreas and other organs. When menin is present it blocks the growth of pancreatic cells and, in that way, prevents cancer.

However, cells of the hormone-producing part of the pancreas, called the islets, need to grow in pregnant women or when people gain weight as a way of providing enough insulin for the burgeoning supply of cells. The increase in pancreas islet cells provides the additional insulin needed for the cells of the body to take up sugar from the blood. After a pregnant woman delivers her child, the pancreatic islets return to their original size.

According to Kim's work in mice, the pancreas accomplishes that adaptive growth by producing less menin during pregnancy. With less of the brake present, the pancreatic islet cells can divide, and this growth provides the additional insulin. Within a week after delivery the menin levels in the mice were back up to normal and the pancreatic islets began shrinking to their original size.

When Kim and postdoctoral scholar Satyajit Karnik, PhD, first author of the study, created mice that produce too much menin, the islets couldn't grow sufficiently during pregnancy and the mice ended up with gestational diabetes.

This suggests that there is an internal code for controlling pancreatic islet growth, a code we intend to crack, Kim said. That code appears to be regulated partly by the level of menin.

Kim's group also showed that a natural way of regulating the amount of menin present in the pancreas is through a hormone called prolactin, which is abundant in pregnant women. Other researchers had previously shown that prolactin during pregnancy stimulates the islet cells to start dividing, but how it accomplished this stimulation was unclear.

Kim and Karnik suspected menin might be the link other researchers had been looking for. To test that idea, they gave prolactin to nonpregnant mice. As predicted, menin levels dropped and the pancreas increased in size, mimicking what is seen during pregnancy.

Kim said that although most of this research relates to menin regulation during pregnancy, similar forces may be at work in obese adults with diabetes. He and Karnik found that obese mice have less menin in the pancreas than mice at a normal weight. That finding suggests that menin may have a central role in obesity-related diabetes as well.

Kim said prolactin may be just one way of regulating menin levels and as a result regulating pancreatic growth. Other hormones may be involved in increasing or decreasing menin in nonpregnant adults.

Understanding the mechanisms of regulating menin should lead to new ways of growing islets for transplantation into people with type-1 diabetes and could lead to new treatments for diabetes in pregnant women or obese adults, Kim said.

Gestational diabetes, which is on the rise nationwide, is becoming more recognized as a significant risk to mothers and their babies. Sen. Hillary Rodham Clinton, D-NY, recently cosponsored a bill aimed at devoting more funding to understanding, preventing and treating the disease.

'Knocking out' cell receptor may help block fat deposits in tissues, prevent weight gain

Thu, 25 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CINCINNATI�University of Cincinnati (UC) pathologists have identified a new molecular target that one day may help scientists develop drugs to reduce fat transport to adipocytes (fat cells) in the body and prevent obesity and related disorders, like diabetes.

Detailed in the Oct. 18 online edition and the November 2007 print issue of the Journal of Clinical Investigation, the findings about a specific cell receptor, known as the adipocyte LDL receptor-related protein 1 (LRP1), provide important clues about the underlying biological mechanisms that control fat transport in the body.

Using genetically altered mice, David Hui, PhD, and his team demonstrated that �knocking out� the LRP1 in fat cells has a direct impact on how many lipids (fats and fat-like substances) are transferred and deposited to different tissues. Hui says the experimental mice gained less weight, stored less fat, tolerated glucose better and expended more energy (due to increased muscle activity) when compared with a control group.

�This receptor is expressed in numerous tissues throughout the body�including the heart, muscles, liver and vascular wall�but its specific functions in the different tissues are still relatively unknown,� says Hui, corresponding author of the study and professor of pathology and laboratory medicine at UC. �Our study has shown that this molecule directly impacts the rate of fat transport in the body, so with further study it could be a new target for drugs aimed at controlling obesity.�

For the study, two independent groups of LPR1-knockout mice were developed: one studied by Hui and his team at UC, the second monitored by collaborator and co-senior author Joachim Herz, PhD, at the University of Texas Southwestern Medical Center.

Researchers discovered that when the LRP1 receptor was active, adipocytes absorbed more fat and triggered a series of cell-signaling activities that caused the body to increase overall fat storage. Although both groups of mice were fed the same low-fat diet, the LRP1 knockout mice stored less fat and experienced no significant weight gain.

�This shows that LRP1 is a critical regulator of lipid absorption in fat cells. Functional disruption leads to fewer lipids being absorbed into the cells and transported throughout the body,� explains Susanna Hofmann, first author of the study and pathology research instructor at UC. �Preventing these interactions in our model prevented the onset of obesity and diabetes.�

Because the genetically altered mice had smaller fat stores to provide warmth, muscular activity naturally increased to raise body temperature and may have also contributed to the lack of weight gain, Hui adds.

Prevailing scientific knowledge says that dietary factors�primarily consumption of triglyceride-rich foods such as fried foods�contribute to obesity and diabetes. When energy intake surpasses energy expenditure, excess calories are deposited as fat in adipose tissue and cause people to gain weight.

'Twinkle after effect' can help retinal patients detect vision loss quickly and cheaply

Tue, 23 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Boston, MA�Scientists at Schepens Eye Research Institute have discovered a simple and inexpensive way for patients with retinal and other eye disease to keep track of changes in their vision loss. In a study published in this week�s PLoS One (October 24, 2007) they demonstrate that a compelling visual illusion known as the induced twinkle after-effect (TAE) can accurately identify the location and breadth of actual blind spots in people with retinal disease. The twinkle after-effect is a �twinkling� that people can see in a blind spot when they stare at a blank screen after staring at a noisy visual target such as a detuned television screen.

�Our hope is that we can make this simple technique available online or on a DVD,� says Dr. Peter Bex, associate scientist at Schepens Eye Research Institute and the principal investigator of the study. �This will be particularly helpful with patients who have glaucoma, diabetic retinopathy or macular degeneration where early detection of changes in vision can impact the effectiveness of treatments.�

According to Bex, many people fail to seek help when they develop blind spots in their vision, because their brains automatically compensate or �fill in� the missing information in their visual field. Since everyone has a blind spot where the optic nerve meets the retina, this perceptual �fill in� process is useful for normally sighted people, allowing them a complete visual image. �But this innate process can mask the effects of serious disorders such as diabetic retinopathy and glaucoma and keep sufferers from seeking help until the vision loss is very serious or they bump into objects they can no longer see.�

The traditional gold standard method for detecting blind spots (scotomas) is very expensive and time consuming and must be done in an ophthalmologist�s office. The technique known as retinal specific microperimetry is a diagnostic tool that costs nearly 50 thousand dollars and requires specialized training to apply.

In 1992 scientists became aware of what they eventually named the �twinkle after effect.� They discovered that when someone looks at a television screen filled with static noise while covering part of their visual field with a small patch, the formerly patched area is left with a twinkling sensation after the noise is turned off and the person looks at a blank screen. The rest of the visual field does not experience the twinkling effect, which was described by one patient as resembling a moving cumulous cloud. �While this discovery was intriguing, it wasn�t clear how it could be used for patients,� says Bex.

In the past several years, Bex and his team began to understand its potential. �We theorized that if people with blind spots stared at a noisy screen, the blind areas would �twinkle� when the screen was turned off and their eyes focused on a blank screen. These �twinkling� blind spot areas could then easily be mapped,� he says.

To test their theory, Bex and his team asked eight patients with macular degeneration to undergo the retinal specific microperimetry test and his �twinkling after-effect� test. The team provided a blank touch screen--after the noisy screen--so patients could outline the twinkling areas with their finger.

The team found that the results of the two tests matched in 75 percent of cases, and visual defects could be detected in areas that are not accessible to conventional microperimetry, confirming his belief that TAE could be used diagnostically. �This tool cannot replace the more sophisticated technique but we believe it is a powerful, simple tool that patients can use daily in the privacy of their home to detect any changes in their vision,� he says. �If a patient detects a change, his or her physician can then study it more closely and offer therapy.�

While the results of this small study are very encouraging, Bex says the next step is to do a larger clinical study.

Ultimately Bex sees this type of test being free to the public on the Internet or distributed through a public health entity. �We really believe this could have a great impact on the visual health of the community,� says Bex.

Exercise improves thinking, reduces diabetes risk in overweight children

Mon, 22 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Just three months of daily, vigorous physical activity in overweight children improves their thinking and reduces their diabetes risk, researchers say.

Studies of about 200 overweight, inactive children ages 7-11 also showed that a regular exercise program reduces body fat and improves bone density.

�Is exercise a magic wand that turns them into lean, healthy kids? No. They are still overweight but less so, with less fat, a healthier metabolism and an improved ability to handle life,� says Dr. Catherine Davis, clinical health psychologist at the Medical College of Georgia and lead investigator.

All study participants learned about healthy nutrition and the benefits of physical activity; one-third also exercised 20 minutes after school and another third exercised for 40 minutes. Children played hard, with running games, hula hoops and jump ropes, raising their heart rates to 79 percent of maximum, which is considered vigorous.

�Aerobic exercise training showed dose-response benefits on executive function (decision-making) and possibly math achievement, in overweight children,� researchers write in an abstract being presented during The Obesity Society�s Annual Scientific Meeting Oct. 20-24 in New Orleans. �Regular exercise may be a simple, important method of enhancing children�s cognitive and academic development. These results may persuade educators to implement vigorous physical activity curricula during a childhood obesity epidemic.�

Functional magnetic resonance imaging studies, which show the brain at work, were performed on a percentage of children in each group and found those who exercised had different patterns of brain activity during an executive function task.

�Look what good it does when they exercise,� says Dr. Davis. �This is an important public health issue we need to look at as a nation to help our children learn and keep them well.�

Unprecedented obesity and inactivity rates in America�s children are impacting health, including dramatic increases in the incidence of type 2 diabetes, a disease formerly known as adult-onset diabetes. Overweight children also have slightly lower school achievement, on average.

�We hope these findings will help persuade policymakers, schools and communities that time spent being physically active enhances, rather than detracts, from learning,� says Dr. Davis.

�There have been several studies that have shown that exercise produces kind of a selective effect, particularly with older adults, in cognitive tasks that require regulation of behaviors,� says Dr. Phillip D. Tomporowski, experimental psychologist at the University of Georgia and a key collaborator.

For this study, researchers gave the children tests that look at their decision-making processes. In the first such studies in children, the researchers found small to moderate improvements in children who exercised as well as a hint of increased math achievement.

�We have a number of studies conducted with animals that examined what influence physical activity has on blood flow, metabolic activity, brain function, glucose regulation, and they all demonstrate the same theme: that physical activity done on a regular basis has a protective effect,� says Dr. Tomporowski. �It doesn�t take too much to make the leap that it might influence developing children as well.�

Looking at the children�s insulin resistance, a precursor of type 2 diabetes in which it takes more insulin to convert glucose into energy, researchers found levels dropped 15 percent in the 20-minute exercise group and 21 percent in the 40-minute group. The control group stayed about the same.

�Increasing volume of regular aerobic exercise shows increased benefits on insulin resistance in overweight children, indicating reduced risk of type 2 diabetes, regardless of sex or race,� they write.

�We also know that if you stop exercising, you lose all the benefits,� adds Dr. Davis. �Exercise works if you do it.�

Adult studies have yielded comparable findings regarding exercise�s impact on insulin resistance and cognition.

The researchers tested oral glucose tolerance, measuring insulin response after children drank a small amount of glucose, before and after the studies. �Once your glucose levels start to rise, it�s called impaired glucose tolerance and that is a precursor of diabetes. It�s called pre-diabetes now,� says Dr. Davis, noting that overweight children typically have higher insulin resistance than their leaner peers. Insulin resistance is an early sign of diabetes risk that appears before glucose levels start to rise. Growth associated with puberty can temporarily increase insulin resistance, Dr. Davis notes, so because some of the children were beginning puberty, they made adjustments for the level of sex hormones.

DEXA scanning, which uses a small amount of radiation to quantify bone, tissue and fat, was used to accurately assess body composition. Executive function was measured using the Cognitive Assessment System and math skills using the Woodcock Johnson Test of Achievement III.

�If physical education were ideal, which it�s not � it�s not daily and it�s not active � then children could achieve this within the school day,� Dr. Davis says, pointing to benefits derived by children exercising just 20 minutes a day. �We are not there. To achieve maximum benefit, we were able to show it will take more than PE.�

Cross-species transplant in rhesus macaques is step toward diabetes cure for humans

Thu, 18 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) St. Louis, Oct. 18, 2007 � With an eye on curing diabetes, scientists at Washington University School of Medicine in St. Louis have successfully transplanted embryonic pig pancreatic cells destined to produce insulin into diabetic macaque monkeys � all without the need for risky immune suppression drugs that prevent rejection.

The transplanted cells, known as primordia, are in the earliest stages of developing into pancreatic tissues. Within several weeks of the transplants, the cells became engrafted, or established, within the three rhesus macaque monkeys that received them. The cells also released pig insulin in response to rising blood glucose levels, as would be expected in healthy animals and humans.

The approach reduced the animals' need for insulin injections and has promise for curing diabetes in humans, says senior investigator Marc Hammerman, M.D., the Chromalloy Professor of Renal Diseases in Medicine. The transplants worked without a need for immune suppression and that is a major obstacle we have overcome.

The researchers' results appear online and will be published in the journal Xenotransplantation in November.

Although the transplants fell short of producing sufficient insulin to cure the macaques' diabetes, Hammerman predicts that with additional research, including the transplantation of additional embryonic pig cells into the animals, he will be able to reduce their need for insulin injections entirely.

The new research follows on the heels of reports by Hammerman and his colleagues demonstrating that transplanted pig pancreatic primordia can cure both type 1 and type 2 diabetes in rats, without using immune suppression drugs. Other scientists have tried different types of pancreatic cell transplants � in animals and humans � as a stepping stone to curing diabetes, but they all require anti-rejection drugs. These drugs must be taken daily to stave off rejection and have adverse effects of their own that limit the success of the transplants.

As a treatment for diabetes in people, pig insulin typically works as well as the human form. Before recombinant DNA technology enabled pharmaceutical companies to manufacture human insulin in the 1980s, pig and cow insulin were routinely given to diabetic patients.

The primates in the current study had type 1 diabetes, the form that occurs when islet cells in the pancreas stop producing insulin all together. The Washington University researchers transplanted 19 embryonic pig pancreatic primordia into each diabetic monkey. Each primordium is smaller than the diameter of a period that ends a sentence and is transplanted into a membrane that envelops the intestines and other digestive organs.

The transplanted cells were retrieved from the pig embryos early in their development, which is believed to render them invisible to the primates' immune system or induce a state of tolerance, either of which eliminates the need for immune suppression.

The researchers determined by multiple methods that the transplanted cells became established within the primates. And as the cells matured, they began to release pig insulin. We found using every method that the cells engraft long-term and, thus, are not rejected by the animals' immune systems, Hammerman says. It's been more than two years since our first transplant was carried out. That particular primate doesn't produce any primate insulin, but has pig insulin circulating in its bloodstream that has reduced by more than 50 percent the amount of injected insulin the animal needs, compared to levels before the transplant. The animals have never received immune suppression drugs.

Two of the macaques remain healthy. One, however, became anemic about six weeks post-transplant and was euthanized a month later after developing acute respiratory distress. The researchers could not find a link between this animal's illness and the pancreatic cell transplants.

The two remaining macaques have each received two transplants of embryonic pancreatic cells. One of the animals has been followed for 23 months after his first transplant, and the amount of insulin he needs to have injected has declined by some 55 percent over baseline levels. The other macaque has been followed for 10 months after his initial transplant, and his need for injected insulin continues to decline over time.

Hammerman and his colleague Sharon Rogers, research instructor in medicine, are leaders in the emerging field of organogenesis, which focuses on growing organs from transplanted embryonic organ precursors known as primordia. Unlike embryonic stem cells, which can become virtually any cell type, primordia are locked into becoming cells of a particular organ.

We are encouraged by these results, Rogers says. The absence of a need for immune suppression in diabetic rats gave us hope that we were on the right track. But many findings in rats do not hold true for species that are more closely related to humans, such as non-human primates. This one did.

The team will now determine how best to eliminate the need for injected insulin in the diabetic macaques that receive transplants, thus demonstrating long-term effectiveness of the technique, and establish the absolute safety of pancreatic primordia transplants. If these experiments succeed, the researchers plan to conduct clinical trials in humans with diabetes.

We hope to find out how to apply our findings to human type 1 and type 2 diabetics because the embryonic pig primordia would represent an unlimited source of tissue for transplantation, Hammerman says.

Low doses of a red wine ingredient fight diabetes in mice

Tue, 02 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Even relatively low doses of resveratrol�a chemical found in the skins of red grapes and in red wine�can improve the sensitivity of mice to the hormone insulin, according to a report in the October issue of Cell Metabolism, a Cell Press publication. As insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes, the findings �provide a potential new therapeutic approach for preventing or treating� both conditions, the researchers said.

The research group also confirmed that increased levels of an enzyme called SIRT1, which earlier studies had linked to longevity, DNA repair, and insulin secretion, improve insulin sensitivity in mice. Resveratrol is known to activate the SIRT1 enzyme.

The results suggest that �red wine might have some benefits for insulin sensitivity, but it needs to be confirmed by further investigation,� said Qiwei Zhai of the Chinese Academy of Sciences. Given the potential complications of drinking alcohol, �an even better option may be to find other natural foods enriched with resveratrol or foods supplemented with resveratrol,� he added, noting that the chemical is also an active ingredient in other plants, including one called Polygonum cuspidatum used in traditional Chinese and Japanese medicine.

Diabetes mellitus, the most common endocrine disorder, currently affects more than 170 million people worldwide and is expected to affect more than 353 million by the year 2030, Zhai said. Type 2 diabetes, which accounts for more than 90 percent of diabetes cases, is characterized by the resistance of body tissues to stimulation by the peptide hormone insulin. Insulin normally lowers blood glucose levels by facilitating the sugar�s uptake, mainly into skeletal muscle and fat tissue, and by inhibiting glucose production in the liver. Currently, alleviating insulin resistance is still one of the key avenues to treating type 2 diabetes.

Earlier studies had reported a connection between SIRT1 and the processes of glucose metabolism and insulin secretion. However, whether SIRT1 was directly involved in insulin sensitivity remained largely unknown, the researchers said.

Now, the researchers report that SIRT1 levels are reduced in insulin-resistant cells and tissues and that treatments that block the enzyme�s function lead to insulin resistance. Furthermore, increased SIRT1 activity improved insulin sensitivity. Similarly, resveratrol�at a dose of just 2.5 mg/kg/day�enhanced insulin sensitivity in cells. That low dose of resveratrol also reduced insulin resistance in animals fed a high-fat diet, the researchers showed.

�We found SIRT1 improves insulin sensitivity, especially under insulin-resistant conditions,� Zhai said. �Furthermore, we found that resveratrol, at a very low dose compared with many previous studies, improves insulin sensitivity via SIRT1.�

The findings suggest that those who drink red wine for the health-promoting benefits of resveratrol might �think about drinking less,� Zhai said. Previously, he noted, the effects of resveratrol seen in mice had implied that humans might need to drink about 120 liters of red wine each day to get enough resveratrol to enjoy the same benefit. �According to our findings, people might need to drink about three liters of red wine each day to get sufficient resveratrol�about 15 mg�for its biological effects.�

Genetic 'roadblock' hoped to inspire future type 2 diabetes research

Tue, 02 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Toronto, ON (October 2, 2007) � A team of Mount Sinai Hospital researchers has found that a �genetic roadblock� identified in a recent study could pave the way toward novel treatments for type 2 diabetes.

In the study, researchers from the Samuel Lunenfeld Research Institute of Mount Sinai Hospital found the first genetic evidence that the elimination of the gene for glycogen synthase kinase-3 (GSK-3) in mice sensitizes the animals to insulin.

Insulin is a hormone that helps control sugar (glucose) levels in the blood. In people with type 2 diabetes, the pancreas does not produce enough insulin, or it is not properly used. As a result, sugar accumulates in the blood rather than being absorbed, stored or burned for energy. The study found that by eliminating GSK-3 in mouse models, more sugar became stored in the liver in response to increased insulin sensitivity, indicating that insulin had become more effective.

The study from the laboratory of Dr. Jim Woodgett, Director of the Lunenfeld, and the first scientist to isolate the GSK-3 genes in 1990, made the cover of the October 3 edition of Cell Metabolism.

�We created a �genetic roadblock� by knocking out this particular gene and this made the mice far more efficient in their ability to use insulin to regulate their blood-sugar levels,� said Dr. Woodgett. �Research creates the best medicine and while potential human treatments are likely still years down the road, this study provides strong evidence that chemical inhibitors of this enzyme will be useful for increasing the effective potency of insulin.�

The study was co-authored by Drs. Katrina MacAulay and Bradley Doble. Dr. MacAulay was inspired to become a medical researcher specializing in diabetes because her sister, Ailsa MacAulay, suffers from this disease.

�I hope our findings will inspire other researchers around the world to develop treatments that will reduce symptoms of this epidemic disease as well as its associated complications, such as heart disease, liver disease or limb amputation,� said Dr. MacAulay.

Currently, more than two million people in Canada suffer from diabetes. It is one of the fastest growing diseases in the country with more than 60,000 new cases diagnosed each year.

Type 2 diabetes makes up about 90 per cent of all cases, with most evidence suggesting that it could be prevented or delayed by maintaining a healthy lifestyle.

�With this research, another piece in the puzzle has been put in place. It advances our understanding of how the complex mechanisms activated by insulin work. Understanding the details of this picture is central to developing new drugs that can help people with diabetes control their blood sugar,� says Dr. Diane T. Finegood, Scientific Director of the CIHR-Institute of Nutrition, Metabolism and Diabetes.

Botched production of insulin molecule may lead to diabetes

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ANN ARBOR, Mich. � Picture a pretzel factory production line, with conveyer belts carrying the dough, formed into unbaked pretzels, down to the oven to be cooked.

Now imagine what would happen if pretzel dough started to overflow the mixer and oozed as a blob onto the conveyor, misshapen, and sticking fast to the dough of the other fully formed, unbaked pretzels. The result: a mess. And if that mess could no longer be conveyed into the oven, the backup of messy dough in the system would get worse and worse, and might eventually shut down the whole factory.

That�s essentially what might be happening in a much smaller kind of factory: the cells that make insulin in the body of people with diabetes.

According to new findings by a team from the University of Michigan Medical School, those tiny factories may shut down because of glitches in the production of a molecule called proinsulin � the precursor, or �dough�, out of which insulin is made.

The insulin factories are called beta cells, and they normally churn out large quantities of insulin within the pancreas. This insulin supply can be released into the bloodstream as needed, to help the body turn sugars from food into energy for cells.

But in people with diabetes, the beta cell factories don�t keep up with the demand for insulin, and sugar builds up in the blood, wreaking havoc on nerves, blood vessel walls and kidneys. And just like a factory that can�t fill a growing number of orders for a hot product, the situation just keeps getting worse and the diabetes progresses.

Scientists have been working to understand why insulin production falters in people with diabetes, and the U-M team has focused on the production and folding of the proinsulin molecule deep within the beta cell. Using a tag that can make proinsulin glow green, they have now found a way to watch proinsulin being made within animal cells, and folded into a shape that can then be turned into insulin. Of course, this also allows them to study what happens when that process goes awry.

In the new paper, published online before print publication in the Proceedings of the National Academy of Sciences, the team details its findings and proposes that proinsulin 'blobs' might lead to beta cell dysfunction and death, which in turn can lead to the start, or progression, of diabetes.

Senior author Peter Arvan, M.D., Ph.D., says, We believe that in the insulin production factory, misfolded copies of newly-made proinsulin can gum up the works in several ways. This paper shows that one of the first things that can happen is that misfolded proinsulin can stick to other proinsulin in the very first stages of production within the endoplasmic reticulum,� the area of the cell where proteins are made.

Arvan, who is chief of Metabolism, Endocrinology and Diabetes at the U-M Medical School and director of the Michigan Comprehensive Diabetes Center, explains that this chain reaction can start with just a few misfolded proinsulin molecules. It can then lead to beta cell shutdown and an insulin shortage. �The misfolded proinsulin does not get exported from the factory, and neither does the normally folded proinsulin made after it,� he says. �Pretty soon, pancreatic beta cells are running out of insulin to secrete in response to the customer's demand for the product � that is, an increase in blood glucose.� And that is a key hallmark of diabetes.

Arvan, who is the William and Delores Brehm Professor of Type 1 Diabetes Research, and first author Ming Liu, M.D., Ph.D., led the research team in developing the techniques needed to visualize proinsulin production and then study problems with the process by following misfolded molecules through the production pathway.

First, the team engineered the gene for human proinsulin to insert a tag that makes the protein fluorescent, but does not interfere with the production, function or secretion of insulin. They inserted the human gene into rat pancreas cells, which allows them to see the human proinsulin being made in live rat cells under the microscope.

Next, the team introduced a mutation into the tagged human insulin gene that causes the proinsulin molecule to fold incorrectly. This allowed them to see what happened when the misfolded human proinsulin and the normal rat proinsulin were produced together inside the same cell.

What they saw was misfolded fluorescent proinsulin getting stuck in the endoplasmic reticulum, so it could not move along normal �conveyor belt� to make insulin. Simultaneously, this blocked the traffic of the normal proinsulin in the same cells. This �protein mess� in the endoplasmic reticulum directly inhibits insulin production in the beta cells, even including insulin production that comes from the otherwise normal rat proinsulin. The beta cells begin to suffer from this, and they ultimately die.

The Arvan lab is also collaborating with other groups to identify new mutations in the proinsulin gene of people with congenital diabetes, and to understand how these mutations may cause a similar �protein mess.�

These mutations are apparently the second most common genetic cause of congenital diabetes, which is a relatively rare genetic illness. Congenital diabetes differs from Type 1 diabetes because congenital diabetes is not caused by an attack by the immune system on the body�s own beta cells, and because it is passed down from parent to child. Arvan and his team suspect that congenital diabetes in babies mirrors the proinsulin misfolding seen in their new study, and in a strain of mice known as Akita mice, which develop diabetes spontaneously after birth.

�The big question -- still to be determined -- is how much of the more common forms of diabetes also involve proinsulin misfolding in beta cells that are stressed to the max to make all the insulin they can,� Arvan notes. �This is a question that we are actively pursuing.�

Joslin researchers uncover potential role of leptin in diabetes

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON�October 1, 2007�A new Joslin-led study has shown that leptin, a hormone known mainly for regulating appetite control and energy metabolism, plays a major role in islet cell growth and insulin secretion. This finding opens up new avenues for studying leptin and its role in islet cell biology, which may lead to new treatments for diabetes. This study appears in the October 2007 issue of The Journal of Clinical Investigation.

Previous in vitro studies suggested that leptin receptors, which are found in tissues throughout the body including the pancreas as well as the brain, mediate leptin-induced inhibition of insulin secretion in islet cells, also known as beta cells. �We wanted to further our understanding of leptin and its role in beta cells independent of its effects in the brain,� said Rohit N. Kulkarni, M.D., Ph.D., principal investigator at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School, who led this study. It is currently not known why obese individuals exhibit a high incidence of diabetes despite high levels of both insulin and leptin circulating in the bloodstream.

To understand the role of leptin in the islets, researchers developed a mouse model (known as a �knock out� or KO mouse) genetically engineered not to produce leptin receptors in the pancreas, while maintaining the receptors in the brain and the rest of the body. Researchers found that the mice lacking leptin receptors in the pancreas showed improved glucose tolerance and greater insulin secretion and beta cell growth. �Since the normal function of leptin is to keep insulin levels from getting too high, the lack of leptin enhances insulin action in the beta cells and promotes insulin secretion, which was the result we expected,� said Dr. Kulkarni.

In the second part of the study, the KO mice and a control group of mice with intact leptin receptors were placed on a high-fat diet. Although both the control and KO mice became obese, only the KO mice developed severe glucose intolerance and insulin resistance, a precursor to the development of diabetes. �These novel results indicate that in the presence of obesity, the combination of insulin resistance in the beta cell and the lack of leptin signaling leads to poor beta cell growth and function leading to glucose intolerance. Interactions between leptin and insulin signaling in the beta cell need to be considered to understand the relationship between diabetes and obesity,� said Dr. Kulkarni.

Obesity is a major risk factor for the development of type 2 diabetes, the most common form of the disease. Other risk factors are age (over 40) and a family history of diabetes, although today it is increasing prevalent in younger people, including adolescents. In type 2 diabetes, islet cells malfunction and the body is unable to compensate by growing more beta cells. By investigating the cellular mechanisms that affect islet cell development and growth, Joslin researchers hope to find better ways to prevent and treat the disease.

Follow-up studies will focus on examining the interactions between insulin and leptin signaling in beta cells and identifying the key proteins found in the pathways that regulate beta cell growth and activity. This could lead to the development of therapeutic drugs that manipulate these proteins to influence beta cell growth and function. �Unraveling the role of leptin in the regulation of beta cell biology will be especially useful in understanding the mechanisms that contribute to beta cell growth with implications for the treatment of both type 1 and type 2 diabetes,� said Dr. Kulkarni.

'Bad carbs' not the enemy, University of Virginia professor finds

Fri, 28 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The latest common wisdom on carbohydrates claims that eating so-called �bad� carbohydrates will make you fat, but University of Virginia professor Glenn Gaesser says, �that�s just nonsense.� Eating sandwiches with white bread, or an occasional doughnut, isn't going to kill you, or necessarily even lead to obesity, he said.

In an article in the October issue of the Journal of the American Dietetic Association, Gaesser analyzes peer-reviewed, scientific research on carbohydrate consumption, glycemic index and body weight and gives the first detailed review of the literature on the correlation between them. His findings run counter to the current consensus on the effects of �good� and �bad� carbohydrates.

Gaesser, author of �It�s the Calories, Not the Carbs� and other books, found that diets high in carbohydrates are almost universally associated with slimmer bodies. More importantly, Gaesser found that consuming lots of high-glycemic foods is not associated with higher body weights. In fact, several large studies in the United States revealed that high-glycemic diets were linked to better weight control.

�There is no reason to be eating fewer carbs � they�re not the enemy,� says Gaesser, a professor of exercise physiology and director of the kinesiology program in the Curry School of Education.

The description of carbohydrates as �good� or �bad� is based on glycemic index, a measure of the quality of the carbohydrate in terms of how much it raises blood sugar. Foods having a high GI are generally thought to be �bad� because they raise blood sugar more than �good� carbs do. Proponents of the glycemic index claim that this leads to excessive insulin secretion, which can cause weight gain and health problems. Foods such as whole-grain breads are said to offer �good� carbs, because they have a lower GI than white bread, for example. Likewise, a glass of pineapple juice has a high GI compared to apple juice.

Several popular low-carb diets use glycemic index as a key feature for optimum weight control, but it is not a reliable description of carbohydrate quality, Gaesser says. Digestion is a complicated process. It�s very difficult to determine the GI of a whole meal, for instance, so it doesn�t really make sense to use GI or �glycemic load� � the glycemic index multiplied by the quantity ingested � as a guide to eating.

After looking at hundreds of articles on large-scale studies using surveys or randomized, controlled trials, Gaesser says they show that �people who consume high-carb diets tend to be slimmer, and often healthier, than people who consume low-carb diets.� Even high-glycemic foods have a place in the diet, he said, attributing that to the overall higher quality of a high-carb diet, which includes more fiber-rich and other nutritional foods.

Gaesser also looked for a clear association between carbohydrate consumption and illnesses, such as type 2 diabetes, heart disease and cancer. He found no compelling evidence that avoiding carbohydrates with a high GI helps prevent these diseases and others. People with diabetes, as well as very sedentary women who are obese, may benefit from lowering their consumption of foods with a high GI, Gaesser says.

Reducing any part of the diet � carbs or proteins or fats � will result in modest weight loss in the short term, if calorie consumption is reduced, he points out. But for long-term weight maintenance, a high-carb, low-fat diet is still the best bet, he said.

Discovery supports theory of Alzheimer's disease as form of diabetes

Wed, 26 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer�s memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer�s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer�s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for �amyloid �-derived diffusible ligand.�)

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer�s disease, the Northwestern study sheds light on the emerging idea of Alzheimer�s being a �type 3� diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer�s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer�s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

�We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,� said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. �Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer�s disease.�

ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer�s disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

�We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer�s brains,� said Klein, a member of Northwestern�s Cognitive Neurology and Alzheimer's Disease Center. �We�re dealing with a fundamental new connection between two fields, diabetes and Alzheimer�s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.�

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

�In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,� said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein�s lab. �These factors suggest that insulin resistance in the brains of those with Alzheimer�s is a response to ADDLs.�

�With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer�s treatment,� said Klein. �I think such drugs could supercede currently available Alzheimer�s drugs.�

Consumption of omega-3 fatty acids associated with decreased risk of type 1 diabetes

Tue, 25 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Preliminary research suggests that in children at increased risk for type 1 diabetes, dietary intake of omega-3 fatty acids was associated with a reduced risk of pancreatic islet autoimmunity, which is linked to the development of diabetes, according to an article in the Sept. 26 issue of JAMA.

�Type 1 diabetes mellitus is an autoimmune disease that is characterized by the destruction of insulin-producing beta cells in the pancreatic islets. Although it is not yet known what initiates the autoimmune process, it is likely that both genetic background and environmental factors contribute to the disease process,� the authors write. Certain dietary factors have been associated with the onset of type 1 diabetes as well as the autoimmune process that leads to the disease.

Jill M. Norris, M.P.H., Ph.D., of the University of Colorado at Denver and Health Sciences Center, Denver, and colleagues examined whether consumption of omega-3 and omega-6 fatty acids are associated with the development of pancreatic islet autoimmunity (IA; development of antibodies against the cells in pancreas that produce insulin) in children. The study, conducted between 1994 and 2006, included 1,770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA (human leukocyte antigen) genotype or having a sibling or parent with type 1 diabetes. The average age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. Fish is the primary source of marine polyunsaturated fatty acids. Childhood diet was measured using a food frequency questionnaire (FFQ).

A case-cohort study (n = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (outer portion of the red blood cell) was examined.

Fifty-eight children became positive for IA during follow-up. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and total omega-6 fatty acid intake, total omega-3 fatty acid intake was inversely associated with IA risk (a 55 percent reduced risk). The association was strengthened when the definition of the outcome was limited to those positive for two or more autoantibodies. In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was associated with a 37 percent decreased risk of IA.

�Our study suggests that higher consumption of total omega-3 fatty acids, which was reported on the FFQ, is associated with a lower risk of IA in children at increased genetic risk of type 1 diabetes,� the researchers write.

Breath analysis offers potential for noninvasive blood sugar monitoring in diabetes

Mon, 24 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Irvine, Calif. � Breath-analysis testing may prove to be an effective, non-invasive method for monitoring blood sugar levels in diabetes, according to a University of California, Irvine study.

By using a chemical analysis method developed for air-pollution testing, UC Irvine chemists and pediatricians have found that children with type-1 diabetes exhale significantly higher concentrations of methyl nitrates when they are hyperglycemic.

The study heralds the potential of a breath device that can warn diabetics of high blood sugar levels and of the need for insulin. Currently, diabetics monitor blood sugar levels using devices that break the skin to attain a small blood sample. Hyperglycemia is common in type-1 diabetes mellitus.

Study results appear this week in the early online version of the Proceedings of the National Academy of Sciences.

�Breath analysis has been showing promise as a diagnostic tool in a number of clinical areas, such as with ulcers and cystic fibrosis,� said Dr. Pietro Galassetti, a diabetes researcher with the General Clinical Research Center (GCRC) at UC Irvine. �While no clinical breath test yet exists for diabetes, this study shows the possibility of non-invasive methods that can help the millions who have this chronic disease.�

In the study, Galassetti, Dr. Dan Cooper and Andria Pontello of the GCRC conducted breath-analysis testing on 10 children with type-1 diabetes mellitus. The researchers took air samples during a hyperglycemic state and progressively as they increased the children�s blood insulin levels.

The breath samples were sent to the laboratory of UC Irvine chemists F. Sherwood Rowland and Donald Blake, who examined the exhaled breath using methods developed for their atmospheric chemistry work. In that work, they measure the levels of trace gases in excess of the parts-per-billion range that contribute to local and regional air pollution. Their research group is one of the few in the world recognized for its ability to measure accurately at such small amounts.

The Rowland-Blake group analyzed the children�s breath samples for more than 100 gasses at parts-per-trillion levels and found methyl nitrate exhaled concentrations to be increased as much as 10 times more in diabetic children during hyperglycemia than when they had normal glucose levels. The methyl nitrate concentrations corresponded with the children�s glucose levels � the higher the glucose, the higher the exhaled methyl nitrates.

Galassetti said that during hyperglycemia, in type 1 diabetes there are more fatty acids in the blood that cause oxidative stress. Methyl nitrate is likely a by-product of this increased oxidative stress. It is commonly present in ambient air at very low concentrations, Galassetti noted, and normally appears in the exhaled breath samples of healthy subjects at parts-per-trillion levels.

�Currently, we are involved with new studies looking at the correlation of other gases with hyperglycemia and other variables, including insulin,� Galassetti said. �Eventually, we hope to put together a full exhaled gas profile of diabetes, and our efforts look promising.�

Both aerobic and resistance exercise improved blood sugar control in people with diabetes

Mon, 17 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In a new randomized controlled trial, both aerobic and resistance exercise improved glycemic/blood sugar control in people with type 2 diabetes. The greatest improvements came from combined aerobic and resistance training.

The study included 251 adults, between ages 39 and 70, who were not exercising regularly and had type 2 diabetes. Participants were assigned to one of four groups: performing 45 minutes aerobic training three times per week, 45 minutes of resistance training three times per week, 45 minutes each of both three times per week, or no exercise.

Each participant was evaluated on changes in A1c value, a number that reflects blood sugar concentrations over the previous two or three months, and is expressed as a percent. An absolute decrease of 1.0 percent in A1c value (e.g. from 8.5 percent to 7.5 percent) would be associated with a 15 percent to 20 percent decrease in risk of heart attack or stroke, and a 25 percent to 40 percent decrease in risk of diabetes-related eye disease or kidney disease.

Both the aerobic and resistance training groups had improved blood sugar control A1c value decreased by about 0.5 percent. The group that did both kinds of exercise had about twice as much improvement as either other group alone�A1c value decreased by 0.97 percent compared to the control group. The control group that did not exercise had no change in A1c value.

�We know that aerobic exercise improves glycemic control,� said Ronald Sigal, MD, the lead author of the study. �But we didn't really know too much about what kind of exercise is the most beneficial and how much of it. In particular there wasn�t much known about resistance exercises when we started planning this study. At the time, some thought that resistance exercise is not useful or even dangerous for some people with diabetes.�

Dr. Sigal, now an associate professor of medicine and cardiac sciences at University of Calgary, oversaw the 26-week study, conducted in centers in Canada.

�And even for people who had fairly good blood sugar control at the beginning of our study, those who did both aerobic and resistance exercise had further improvements in glucose control.�

�The bottom line,� said Dr. Sigal, �is that doing both aerobic and resistance exercise is the way to maximize the effects of exercise on blood glucose control in type 2 diabetes.�

In an accompanying editorial, William E. Kraus, MD and Benjamin D. Levine, MD, say, �Imagine an inexpensive pill that could decrease the hemoglobin A1c value by 1 percentage point, reduce cardiovascular death by 25 percent, and substantially improve functional capacity (strength, endurance, and bone density). Diabetes experts would be quick to incorporate this pill into practice guidelines and performance measures for diabetes. (These) study results should simulate all clinicians to include exercise assessment and counseling into every clinic visit.�

Immune police recognize good and bad guys in the body

Fri, 14 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Immune system police are as good at recognizing bad guys, such as bacteria and viruses, as they are our own tissue, researchers say.

The finding may cause a stir in the scientific community, which has long held that regulatory T cells or Tregs, preferentially respond to body proteins, or self antigens, rather than non-self antigens, invaders such as viruses and bacteria.

Now, Medical College of Georgia immunologists report in the September issue of Immunity that Tregs, similarly to other T cells, respond stronger and more frequently to foreign substances than to the body�s own antigens.

Fortunately, the potential conflict between na�ve and regulatory T cells, in which the former lead the attack against invaders and the latter try to protect invaders, usually doesn�t exist, the scientists say.

That�s probably because other types of immune cells come to help T cells fight an infection, says Dr. Rafal Pacholczyk, a corresponding author for the study.

�During the normal immune response, Tregs sit in the back seat and, in most cases, don�t interfere,� says Dr. Leszek Ignatowicz, also a corresponding author.

Still, emerging therapies to fight autoimmune diseases, such as arthritis, multiple sclerosis and type 1 diabetes, by boosting the total number of Tregs could unintentionally upset the balance between na�ve T cells and Tregs, they say.

�Regulatory cells always suppress immunity, whether it�s to a virus, bacteria or our own tissue,� says Dr. Ignatowicz.

�We have to be really careful with manipulating regulatory T cells as a whole,� adds Dr. Pacholczyk. �If we want to promote more regulatory cells in the body, we have to find a way to promote only those in which specificities are known.�

Oral insulin, which appears to boost the number of Tregs that recognize and protect insulin-producing pancreatic cells from the immune system, is a good example of how this targeted promotion may work for type 1 diabetes, they say.

To determine what antigens Tregs can recognize, Drs. Pacholczyk and Ignatowicz did side-by-side studies of antigen receptors expressed on na�ve T cells and Tregs.

�Here, we could quantitatively compare proportions of how many regulatory cells or how many non-regulatory cells see non-self versus self antigens, and we found these proportions to be similar,� says Dr. Ignatowicz. �We found regulatory cells respond to cells presenting non-self antigens as frequently as na�ve T cells.�

Researchers report that 70 percent of the most frequent receptors found on na�ve T cells also were found on Tregs. Since receptors define what the individual T cell recognizes, it provides additional evidence that na�ve T cells and Tregs see the same thing, they say.

Drs. Pacholczyk and Ignatowicz reported in the August 2006 issue of Immunity that Tregs, like na�ve T cells, learn what to recognize in the thymus. They also reported that most Tregs that mature in the thymus retain their regulatory properties and do not later convert to na�ve T cells as was previously believed. This finding emphasized the role of the thymus as the primary site where Tregs differentiate and acquire their unique inhibitory functions, they say.

Although, the majority of T cells that may harm healthy body tissue are eliminated in the thymus, some errant autoreactive cells can escape and cause autoimmune disease. Tregs previously believed to primarily recognize self-tissue with the idea of protecting it are considered the antithesis of these autoreactive cells.

�It was believed that regulatory cells are baptized autoreactive cells,� says Dr. Ignatowicz. �They are like bad boys that went good,� since they also recognize self tissue but seek to protect it.

Yet scientists kept running into the reality that some regulatory cells also were recognizing � and potentially protecting � invaders such as bacteria and viruses.

The MCG scientists say because both T cell populations are educated in the thymus, it is not surprising that they recognize the same things.

Drug could improve pregnancy outcomes in wider range of women with insulin resistance

Thu, 06 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) St. Louis, Sept. 6, 2007 � Women who are obese, have type 2 diabetes or a family history of type 2 diabetes could one day have more successful pregnancies because of a study at Washington University School of Medicine in St. Louis.

This study, performed in mice, suggests that Metformin, the most commonly prescribed anti-diabetes drug, could potentially improve pregnancy outcomes in women with insulin resistance.

�We found that embryos of insulin-resistant mice also have some degree of insulin resistance, and if we correct the insulin resistance in the embryo with this drug, we improve the quality of the embryo,� says Kelle Moley, M.D., lead author and professor of obstetrics and gynecology.

The finding, published online in Diabetes, suggests that Metformin could benefit women with type 2 diabetes or polycystic ovary syndrome (PCOS). About 8 percent of women trying to conceive have insulin resistance, Moley says, and even more are suspected to be borderline. In some cases, a family history of type 2 diabetes or being overweight may be the only indication that the patient may be prone to insulin resistance.

Metformin is often given to women with PCOS, an endocrine disorder that affects insulin and results in higher rates of miscarriage. These women often share the same pregnancy complications as women with type 2 diabetes and obesity.

Recent studies have shown that metformin not only aids conception in women with PCOS but also reduces the high miscarriage rates; however, how the drug does this has been unclear.

Using early-stage mouse embryos, Moley and her colleagues showed for the first time that metformin improves insulin action in insulin-resistant embryos. That allowed the embryos to absorb glucose, an important energy source, and prevented the death of cells in the embryos. As a result, the embryos were more likely to successfully implant in the uterus and to continue growing.

Moley's group also identified the molecular mechanism that accounts for metformin's positive effects. They found the drug triggers an important sensor of the energy level of cells, which sets off a chain of reactions that help insulin do its job. Previously it was not known that this sensor molecule was active in early embryos.

Moley hypothesizes that in insulin-resistant women, high levels of insulin and related factors cause their embryos to compensate by shutting down insulin signaling mechanisms. That impairs the early embryo�s ability to take in glucose at a critical stage of development and can lead to pregnancy failure.

�We found that Metformin improves glucose uptake and improves the survival of the early embryo as a result,� Moley says. �Mouse embryos in a high-insulin environment that were not exposed to Metformin did not survive.�

Most miscarriages are due to chromosomal abnormalities. But Moley says this study provides new scientific evidence that miscarriages related to insulin resistance possibly could be avoided through the use of metformin.

�This will help physicians know better how to treat these women and reassure them that they�re being correctly treated for their medical problems and that their babies will benefit from that treatment,� she says.

Sugary drinks, not fruit juice, may be linked to insulin

Wed, 05 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON (Sept. 5, 2007) � Steady increases in consumption of sugar-sweetened beverages over the last several decades, as well as rates of Type 2 diabetes mellitus, led nutritional epidemiologists at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University and colleagues to explore the relationship between sugar-sweetened beverage consumption and insulin resistance, a precursor to Type 2 diabetes. Their findings suggest that higher consumption of sugar-sweetened drinks, but not 100 percent fruit juice, may be associated with insulin resistance, even in otherwise healthy adults.

�Study participants who consumed two or more sugar-sweetened beverages per day had significantly higher fasting blood levels of insulin as compared to participants who did not report consuming any such beverages, regardless of age, sex, weight, smoking status, or other dietary habits,� says senior author Paul Jacques, DSc, director of the Nutritional Epidemiology Program at the USDA HNRCA and professor at the Friedman School of Nutrition Science and Policy at Tufts University. �Higher fasting levels of insulin mean these study participants are more at risk for developing Type 2 diabetes. In contrast,� he says, �consumption of 100 percent fruit juice was not significantly related to any of our measures of insulin resistance.�

Study participants were 2,500 healthy men and women in the Framingham Offspring Study, a community-based study of cardiovascular disease among offspring of people in the original Framingham Heart Study. Participants reported their usual dietary intake for the previous year, which researchers used to determine average intakes of sugar-sweetened drinks (regular and caffeine-free colas and other carbonated beverages containing sugar), diet soft drinks (low-calorie colas with and without caffeine and other low-calorie carbonated beverages), and fruit juice (e.g., apple juice or apple cider, orange juice, and grapefruit juice). One serving of a sugar-sweetened drink or diet soda was considered equivalent to 12 fluid ounces, or a regular-sized can of soda. One serving of fruit juice was considered equivalent to six fluid ounces.

The researchers obtained blood samples from participants who fasted for at least eight hours, and measured the participants� blood levels of insulin as well as glucose. High fasting glucose levels, like high fasting insulin levels, are a pre-cursor to Type 2 diabetes. �Unlike fasting insulin levels, fasting glucose levels were not significantly different between those who consumed sugar-sweetened drinks and those who did not,� says Jacques, �However, participants consuming two or more daily servings of 100 percent fruit juice had modestly lower fasting glucose levels, compared with those who did not consume fruit juice.� Although this observation might be due to the additional nutrients or other phytochemicals found in the juices, Jacques notes this also may be a consequence of the healthier lifestyle and dietary habits of fruit juice consumers. They were less likely to smoke than non-consumers, and consumed diets relatively lower in saturated fat and higher in total fiber.

Despite these results, Nicola McKeown, PhD, corresponding author and scientist in the Nutritional Epidemiology Program at the USDA HNRCA, does not advise increasing consumption of fruit juice. �While 100 percent fruit juice can be a healthful beverage, too much fruit juice can add excess calories and sugar to the diet. Whole fruit is often a better choice.�

Jacques and McKeown also caution that their results cannot be used to determine cause-and-effect relationships among caloric and non-caloric sugar-sweetened beverage consumption and insulin resistance. �It could be that people who drink sugar-sweetened beverages have other unhealthy behaviors that we did not account for,� says McKeown. �Sugar-sweetened drink consumption may prove to be an important determinant of insulin resistance, but more long-term studies of diverse populations that incorporate the use of more direct measures of insulin resistance are needed.� In the meantime, the researchers suggest that people continue to follow the recommendations in the 2005 Dietary Guidelines for Americans, increasing consumption of water while limiting intake of calorically sweetened, nutrient-poor beverages.

Environmental stress probed in cardiovascular disease, diabetes

Wed, 05 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) How environmental stress contributes to cardiovascular disease and type II diabetes is under study at the Medical College of Georgia.

The study, which follows 523 pairs of twins, is funded by a $1.7 million continuation grant from the National Institutes of Health.

�Cardiovascular disease and type II diabetes and their co-morbidity pose an important health challenge to the United States,� says Dr. Frank Treiber, vice president for research and principal investigator on the study. �What we�re looking at are environmental issues and the role they play in causing these diseases. It�s often the combination of genetic and environmental risk factors that is driving the development of these diseases.�

Researchers have long thought that environmental stress factors � things like family dysfunction, low socioeconomic status and discrimination � play an important role in cardiovascular disease and type II diabetes, but little is known about physiological factors that link stress to the diseases� development.

�How those factors are related to physiological changes that then cause the development of subclinical disease is unknown at this point,� Dr. Treiber says. �A twin study allows you to tease out the genetic contributions by comparing identical and fraternal twins.�

MCG researchers have been studying the twin sets since 1997. When they started the study, their average age was 10; they will be 19, on average, as they start the new study.

By comparing identical twins, who share the same genetic material, to fraternal twins, who are, on average, like other siblings in terms of the genetic material they share, researchers can determine whether risk factors such as high blood pressure and insulin levels are due to genetics or environmental factors.

They believe the cumulative impact of stressful environments will predict cardiovascular disease and type II diabetes.

Researchers will evaluate them two more times over the next four years, asking about stress factors, including their living environments and how they cope with stress.

�The twin design allows you to assess whether they are experiencing the same environmental factors now as when they were younger and in the same household,� Dr. Treiber says. �Early in life, children tend to model their parents� behavior in how they cope with stress and perceive the world. As they�ve gotten older, they�ve been exposed to different things, different environments. By comparing them and determining whether they�ve developed early signs of these diseases, we can tell how much is attributable to genetics and how much is environmental stress.�

Past phases of the study have revealed that among both the black and white twins, genetics account for about half of the differences in blood pressure and reactions to stress.

With the current phase, researchers also hope to find out whether the black twins, whose race tends to develop hypertension earlier and more often than whites, are more impacted by stress. One theory is that blacks have a higher risk of stress due to things such as discrimination, unfair treatment and unsafe neighborhoods.

�The value of the longitudinal study is that we�ll be able to look at the changes over time,� Dr. Treiber says. �Not only the physical changes as they mature, but also the changes in their social and emotional development.�

�We have a greater chance to intervene and alter environmental factors, for example by teaching people how to better deal with stress,� says Dr. Harold Snieder, MCG adjunct professor of pediatrics, chair of the Genetic Epidemiology and Biostatistics Unit at the University of Groningen, The Netherlands, and a co-investigator on the study.

How insulin TORC2 blood sugar levels: glowing mice light the way

Wed, 05 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) La Jolla, CA � With the help of genetically engineered mice whose livers turned into glowing light bulbs, researchers at the Salk Institute for Biological Studies have illuminated the underpinnings of an insidious and growing health concern� type II diabetes.

In the study published in the September 5 advanced online edition of Nature, the researchers report that a protein called TORC2 serves as a key biochemical control point linking feeding, insulin, and elevated blood sugar production in the liver. The findings highlight TORC2 and an enzyme called SIK2 as potential drug targets for treating type II diabetes.

An estimated 21 million Americans have �adult-onset,� or type II diabetes, and another 54 million have a condition called pre-diabetes where blood sugar levels remain abnormally high even after fasting. According to the Centers for Disease Control and Prevention, one in three Americans born in 2000 will develop diabetes, an incurable disease that can lead to blindness, kidney failure, heart disease, and other serious debilitations.

The problem starts during gluconeogenesis�a process by which blood sugar is produced in the liver, explains Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. During fasting, gluconeogenesis maintains blood sugar levels by increasing glucose production. After a meal, the hormone insulin normally turns down gluconeogenesis ensuring that blood sugar levels don�t rise too high. �But in people with insulin resistance, blood sugar levels are elevated because gluconeogenesis continues when it shouldn�t, increasing the risk of developing type II diabetes,� Montminy says.

Twenty years ago, Montminy discovered a metabolic switch, a protein called CREB that responds to various physiological signals by turning on and off different gene networks in the body. During periods of fasting when blood sugar stocks run low, for example, CREB turns on gluceoneogenesis in the liver. Recently, Montminy�s team identified a second essential component of the CREB switch, a protein called TORC2, that binds to CREB and enables the switch to work.

While the researchers had established that TORC2 was essential to sugar production during fasting, they were keenly interested in understanding the protein�s role during feeding. That knowledge might clue them in to the causes of insulin resistance.

To learn how feeding and insulin affect TORC2, the researchers, led by post-doctoral fellows Renaud Dentin and Yi Liu, inserted into laboratory mice the luciferase gene, which produces the glow of firefly tails. They rigged the gene in such a way that it could only be turned on in the liver by the CREB/TORC2 switch. When the gene was turned on, the luciferase enzyme caused the liver to light up. Using a sensitive camera, the light�a direct measure of CREB/TORC2 activity�could be detected and measured from outside of the live mice. Using biochemical and genetic techniques to change the levels of various molecules in the pathway, including insulin and TORC2, the researchers measured the effect of these changes on the amount of light emitted from the liver.

The experiments revealed that the rise in insulin during feeding turned off the CREB/TORC2 switch. Insulin first activated a liver enzyme called SIK2, which in turn inactivated TORC2 by chemically tagging it with a phosphate group. The extra phosphate group caused TORC2 to leave the cell nucleus where it needed to be to turn on genes. Once the protein left the nucleus, the researches discovered, it was destroyed by the cell�s protein degradation machinery or proteasome.

�You need TORC2 to be downregulated by phosphorylation during feeding. If you don�t do that, then the whole gluconeogenic program stays on, and glucose levels go up,� Montminy says. Understanding these key roles of TORC2 and SIK2, he emphasizes, points to their potential as drug targets for stemming the rising tide of fasting blood sugar.

But the glowing mice might one day do more than illuminate the relationship between feeding, fasting, and the CREB/TORC2 switch. �Because the luciferase mice provide a direct look at glucose metabolism in the liver, this imaging approach may be useful in evaluating potential drugs for the treatment of type II diabetes,� says Montminy.

Combination drug therapy for blood pressure may reduce cardiovascular outcomes for diabetes patients

Sun, 02 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) By 2030, an estimated 350 million people will be living with diabetes worldwide. Individuals with type 2 diabetes are at an increased risk of cardiovascular outcomes including heart attack, stroke, and microvascular outcomes such as degenerative eye disease. Current guidelines recommend the lowering of blood pressure for people with type 2 diabetes to reduce the risk of such events, though a strategy to reduce blood pressure regardless of baseline blood pressure (ie, including people with diabetes who do not have raised blood pressure) has not been proven in randomised trials to date.

The ADVANCE trial recruited around 11000 individuals with type 2 diabetes from 215 medical centres in 20 countries across the world. Individuals were randomised to receive either a combination of the ACE inhibitor perindopril and the diuretic indapamide or placebo and were followed up for over four years.

Individuals given active therapy had an average reduction in systolic blood pressure of 5-6 mm Hg and diastolic blood pressure of 2-2 mm Hg compared with the placebo group. The relative risk of a major macrovascular or microvascular event was reduced by 9% (15-5% active vs 16-8% placebo). The separate reductions in macrovascular and microvascular events were similar but were not statistically significant by themselves.

The relative risk of death from cardiovascular disease was reduced by 18% (3-8% active vs 4-6% placebo), and death from any cause was reduced by 14% (7-3% active vs 8-5% placebo). The results were not dependent on baseline blood pressure or whether individuals were using other treatments for diabetes.

One of the authors, John Chalmers (The George Institute, University of Sydney, Australia), comments: -In summary, the results of ADVANCE indicate that the routine administration of a fixed combination of perindopril and indapamide to a broad range of patients with diabetes reduces the risks of death and major macrovascular or microvascular complications, irrespective of initial blood pressure level or ancillary treatment with the many other preventive treatments typically provided to diabetic patients today. The study treatment was well tolerated, needed little monitoring or titration and is, therefore, suitable for use in a wide range of clinical circumstances worldwide. If the benefits seen in ADVANCE were applied to just half the population with diabetes worldwide, more than a million deaths would be avoided over 5 years. For these reasons, there is now a case for considering such treatment routinely for patients with type 2 diabetes.-

In an accompanying Comment, Norman M Kaplan (University of Texas Southwestern Medical Center, USA) cautions against over-interpretation of ADVANCE. He concludes: -The fixed combination of perindopril and indapamide could be the best possible protector against hypertension-related consequences for patients with type 2 diabetes, but I believe that other drugs-if they lower blood pressure as much and do not have metabolic side-effects-would be as protective as this combination treatment. As has been said many times by many experts: in most circumstances, lowering the blood pressure is what counts, not the way by which it is lowered.-

Treating diabetes during pregnancy can break link to childhood obesity

Tue, 28 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) August 28, 2007 (Oakland, Calif) -- Treating diabetes during pregnancy can break the link between gestational diabetes and childhood obesity, according to a Kaiser Permanente study featured in the September issue of Diabetes Care.

The largest study of its kind, this research shows that the risk of childhood obesity rises in tandem with a pregnant woman�s blood sugar level and that untreated gestational diabetes nearly doubles a child's risk of becoming obese by age 5 to 7. The study also shows for the first time that by treating women with gestational diabetes, the child�s risk of becoming obese is significantly reduced. In fact, children whose moms were treated for gestational diabetes had the same risk for becoming obese as children whose mothers had normal blood sugar levels.

Researchers at Kaiser Permanente�s Center for Health Research (CHR) in Portland and Hawaii used the organization�s integrated databases to analyze medical records of 9,439 mother-child pairs. The subjects were members of the health plan in Oregon, Washington and Hawaii and gave birth between 1995 and 2000. The authors found that treating gestational diabetes lowers the child's risk of becoming obese during childhood to the same levels of those pregnant mothers with normal blood sugar levels.

Gestational diabetes, the condition in which pregnancy triggers insulin resistance and raises the woman�s blood glucose level (hyperglycemia), affects up to 8 percent of pregnant women each year in the United States. The rate of childhood obesity in this country more than doubled in the last two decades, so much so that it is now one the nation�s fastest growing health conditions. Nearly 7 million overweight and obese children in the United States today will grow up to become overweight or obese adults.

Hyperglycemia during pregnancy is clearly playing a role in America's epidemic of childhood obesity, said Teresa Hillier, MD, MS, an endocrinologist and senior investigator at CHR Northwest and Hawaii, and the lead author of the study. The key finding here is that the risk of overweight and obese children rises in step with higher levels of blood sugar during pregnancy. The good news for pregnant women is that by treating gestational diabetes, your children's risk of becoming overweight or obese drops considerably.

My advice to pregnant women is three-fold: Discuss gestational diabetes screening with your doctor, usually between weeks 24 and 28 of pregnancy; if you have gestational diabetes, work with your physician to treat it, and stick with the treatment during your pregnancy. It's the best thing you can do to reduce your child's risk of obesity, said Dr. Hillier.

Funded by a grant from the American Diabetes Association, the study was made possible by Kaiser Permanente's interlinked, computerized databases. As the nation's largest and oldest integrated care delivery system, Kaiser Permanente researchers can anonymously review patient records dating back many years and look for connections with the patient's family members and other aspects of the members� health.

The women in the study were screened during pregnancy for blood sugar level and gestational diabetes. The women's children were measured for weight between the ages of 5 and 7 � the so-called adiposity rebound period, a strong predictor of adult obesity. The relationship between maternal blood sugar and childhood obesity was then analyzed.

Children of mothers with high levels of blood sugar who were untreated were 89 percent more likely to be overweight and 82 percent more likely to be obese by the time they were 5 to 7 years of age, compared to children whose mothers had normal blood sugar levels during pregnancy.

�The obesity risk of children whose mothers had the highest blood sugar levels�and were treated for gestational diabetes�was not statistically different than children of mothers with normal blood sugar levels. This suggests that the 'metabolic imprinting' for childhood obesity that results from gestational diabetes in pregnant women may be reversible, Hillier said.

Novel method enables genomic screening of blood vessels from patient tissue

Tue, 28 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio � Scientists have developed a new method of capturing a complete genome-wide screening of blood vessel cells in their actual disease state, advancing the potential for genetic research on the tissue responsible for delivering nourishment that can accelerate the growth of both a cancer tumor or wound healing.

The method is not just a bonus for translational research, but also has made it possible to determine that genes long associated only with cancer are also expressed in chronic wounds.

The team of scientists, based at Ohio State University Medical Center, is using laser capture microdissection to pluck blood vessels, or if need be a single cell, from human wound tissue as part of a major research initiative looking for mechanisms underlying chronic wounds.

They published a description of the research method in the Proceedings of the National Academy of Sciences scheduled for online publication this week and print publication on Sept. 4.

�We have enabled the capture and genome-wide screening of blood vessels from biopsy material regardless of disease,� said Dr. Chandan Sen, executive director of Ohio State�s Comprehensive Wound Center and senior author of the paper. �It�s a big leap in our ability to perform high-resolution vascular biology research utilizing patient material.�

The method is superior to previous methods of cell biology research because it allows scientists to study clinical tissue material with cell-specific resolution, said Sen, also professor and vice chair of surgery and deputy director of Ohio State�s Davis Heart and Lung Research Institute. Standard research methods, such as examining cells in the lining of vessel walls, are conducted by cell culture, meaning the cells are removed from their disease environment and placed in a culture dish. The culture conditions do not mimic the microenvironment of the cells when they are in their actual diseased state.

Studies that examine biopsy tissue from patients typically study extracts of the entire biopsy, which represents a mix of numerous tissue and cell types. Such whole-biopsy extract studies do not provide precise cell-specific information, Sen noted. The new approach identifies blood vessels in the human tissue in a matter of less than five minutes, followed by robot-assisted rapid dissection and collection of blood vessels from serial tissue sections. The collected tissue material can then be subjected to genome-wide screening.

Blood vessels are critical components of multiple diseases, so their quick identification and analysis at the cellular level has broad implications.

�The main strategies of limiting cancer are to stop the vascular supply that feeds the tumor. So if you know the biology of the blood vessel feeding the tumor, you can halt that action and the tumor can no longer grow,� Sen said. �In the case of chronic wounds, the tissue can grow only if blood vessels bring food and fuel � say, glucose and oxygen � to power the healing process. �In both diseases, you need a clear understanding of vascular biology.�

The tissue screened for the study of the genetics of wound healing is supplied by a new wound tissue bank at Ohio State, which holds more than 500 samples collected from seven U.S. centers affiliated with National Healing Corp. Ohio State�s Comprehensive Wound Center has a partnership with National Healing Corp., a private Florida company that manages 20 percent of the nation�s wound-healing centers

�Traditionally, in wound healing, there has been no way to tell what�s going on in the wound except by visualization and what a biopsy says � whether it�s infected or cancerous. We�re advancing the depth and level of this knowledge in our investigation,� said Dr. Gayle Gordillo, director of the plastic surgery research lab at Ohio State�s Medical Center and co-author of the paper.

Current studies are ongoing to test which genes predict healing and which genes are expressed in wounds that are chronic and predict a failure to heal. The researchers are taking biopsies from clinic patients with both healing and non-healing wounds and using the laser capture microdissection to study a homogeneous cell population and run the full genome screen.

The laser capture technology allows the scientists to zero in on the microvessels, which are expected to sprout when tissue is healing. If the microvessels in chronic wound samples are not sprouting, the researchers can then turn to endothelial cells � in the lining of blood vessel walls � to see if there is a genetic basis in those cells for why wounds do or don�t heal.

The first author of the study, Dr. Sashwati Roy, assistant professor of surgery, is a molecular biologist whose expertise lies in developing the method and sorting out the meaning of the data collected from the genes and identifying candidate genes involved in healing.

�One little genetic mutation can affect a person�s response to medications. The laser capture microdissection represents a powerful approach to conduct cell biology research utilizing patient biopsy material,� Roy said.

�The basic assumption has been that the blood vessels in intact skin and wounds are the same. What we�re seeing instead is that genes thought to be uniquely expressed in cancer are also expressed in wounds. None of these genes has been studied in wound healing,� Sen said. �So ultimately, this novel approach helps formulate new clinically relevant hypotheses. It�s a highlight for patient-based research.�

Focus on families aims to curb diabetes spread

Wed, 22 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Family lifestyles and their impact on the health of individual family members will be the focus of a new approach to preventing diabetes.

In the first study of its kind in Britain, researchers from the Universities of Edinburgh and Glasgow will test whether involving whole families in weight loss and fitness initiatives is effective in preventing the development of type 2 diabetes among high-risk family members.

The �1m study will focus specifically on people of Indian and Pakistani origin, who are five times more likely to develop late onset diabetes than the rest of the population.

Researchers will look particularly at families with at least one member who has a high risk of diabetes, possibly because they are overweight or do little exercise. The study, which is currently recruiting participants living in Edinburgh and Glasgow, will encourage all family members to adopt a healthy lifestyle with the aim that this motivates and supports those individuals at risk.

The study is funded by the National Prevention Research Initiative and aims to recruit 300 families. Dieticians will visit them at home over the next three years and provide culturally-specific advice on nutrition and exercise.

Researchers hope to reduce the incidence of type 2 diabetes by 50 per cent, and believe that by focusing on high-risk families, they will find strategies that can be applied more widely.

Raj Bhopal, Professor of Public Health at the University of Edinburgh and project leader, said: �Diabetes is increasing rapidly as we get more obese and less active. If we don�t take urgent action, it will spread in epidemic proportions.

�This family-based approach has never been tested before, but by involving the siblings and parents of at-risk individuals, we hope to provide a motivational and supportive strategy that could prevent diabetes not only in the UK, but on a global scale.�

Diabetes currently affects two million people in the UK, of which 90 per cent have type 2 (or late onset) diabetes that can lead to heart disease, stroke and blindness.

The condition develops when the body cannot make enough insulin, or when the insulin that is produced does not work properly (known as insulin resistance).

Jim McCaffery, Director of Acute Services and Workforce and executive lead for equality and diversity, NHS Lothian said: �We are delighted to be involved with this study. It is important that the health needs of all individuals are met and that we are sensitive to their needs.

�NHS Lothian is committed to meeting the equality and diversity needs of the local population by continually improving services and reducing health inequalities.�

Diabetes appears to increase risk of death for patients with acute coronary syndromes

Tue, 14 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Individuals with diabetes and acute coronary syndromes (ACS) such as a heart attack or unstable angina have an increased risk of death at 30 days and one year after ACS, compared with ACS patients without diabetes, according to a study in the August 15 issue of JAMA.

The presence of elevated blood glucose levels, diabetes mellitus, or both contributes to more than 3 million cardiovascular deaths worldwide each year. With the increase in obesity, insulin resistance, and the metabolic syndrome, the worldwide prevalence of diabetes is expected to double by the year 2030, the authors write. They add that more than 1.5 million adults in the U.S. were newly diagnosed with diabetes in 2005, and nearly 65 percent of individuals with diabetes die from cardiovascular disease in the U.S., establishing it as the leading cause of death among this growing segment of the population. The effect of diabetes on the risk of death following ACS is uncertain.

Sean M. Donahoe, M.D., of Brigham and Womens Hospital and Harvard Medical School, Boston, and colleagues evaluated the independent effect of diabetes on risk of death following ACS at 30 days and 1 year using a large clinical trial database that included ACS. The study consisted of an analysis of patients with diabetes enrolled in randomized controlled trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62,036 patients (46,577 with ST-segment elevation myocardial infarction [STEMI; a certain pattern on an electrocardiogram following a heart attack] and 15,459 with unstable angina/nonSTEMI [UA/NSTEMI]), of whom 10,613 (17.1 percent) had diabetes.

The researchers found that the rate of death was significantly higher among patients with diabetes than among patients without diabetes at 30 days following either UA/NSTEMI (2.1 percent vs. 1.1 percent) or STEMI (8.5 percent vs. 5.4 percent). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with a nearly 80 percent increased risk of death at 30-days after UA/NSTEMI, and 40 percent increased risk of death at 30-days after STEMI.

At 1 year, diabetes remained a significant independent factor associated with all-cause death for patients presenting with UA/NSTEMI (65 percent increased risk of death) or STEMI (22 percent increased risk of death). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2 percent vs. 8.1 percent).

Despite modern therapies for ACS, diabetes conferred a significant independent excess mortality risk at 30 days and 1 year following ACS. Current strategies are insufficient to ameliorate the adverse impact of diabetes. Given the increasing burden of cardiovascular disease attributable to diabetes worldwide, our study highlights the need for a major research effort to identify aggressive new strategies to manage unstable ischemic heart disease among this high-risk population, the authors conclude.

UCLA researchers identify markers that may predict diabetes in still-healthy people

Tue, 14 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In the first large scale, multiethnic study of its kind, researchers at UCLA have confirmed the role played by three particular molecules known as cytokines as a cause of Type 2 diabetes, and further, have identified these molecules as early biological markers that may be used to more accurately predict future incidences of diabetes among apparently healthy individuals.

Reporting in the August 15 issue of the journal Archives of Internal Medicine, Simin Liu, professor of epidemiology and medicine with a joint appointment in the School of Public Health and the David Geffen School of Medicine at UCLA, and colleagues have identified three inflammatory cytokines (cytokines are messenger molecules) tumor necrosis factor-alpha (TNF-á); interleukin-6 (IL-6); and high-sensitivity C-reactive protein (hs-CRP) that may be one of the causes of type 2 diabetes which afflicts roughly seven percent of the U.S. population.

Type 2 diabetes is the most common form of diabetes; about 90 to 95 percent of people who have diabetes have type 2. People with this condition produce insulin, but either their bodies dont make enough of it, or cant effectively use it.

Low-grade chronic inflammation of the body, which is reflected by elevated levels of inflammatory cytokines in the blood stream, may promote insulin resistance in the liver, muscles, and the vascular endothelium cells, the layer of thin, flat cells that lines the interior surface of blood vessels. Such inflammation can last for years before leading to type 2 diabetes, cardiovascular disease, or hypertension.

A blood test that looks for high levels of inflammatory cytokines could serve as an accurate predictor of diabetes in still-healthy people, years ahead of the traditional risk factors of obesity or insulin resistance. The finding also has implication for cancer research as well, said Liu, since people with diabetes are at greater risk of developing breast and colon cancers.

This is a final confirmation of earlier studies about the underlying biology behind type 2 diabetes, said Liu, who is also a member of the UCLA Jonsson Comprehensive Cancer Center. But those studies, he said, were either very small or animal studies. By comparison, he said, their study was more extensive in scale and involved human study volunteers. Our study identified 1,600 new cases of diabetes and measured the blood markers before they developed the disease.

The researchers took advantage of the Womens Health Initiative Observational Study (WHIOS), an ongoing, long term study that was designed to examine the association between behavior, socioeconomic status, diet, and other factors and the effect on a womans health. Liu and colleagues took baseline level measurements of inflammatory cytokines in apparently healthy women without any signs of diabetes who were between the ages of 50 and 79 years-old, then tracked their health for the next six years. The WHIOS study involved some 82,000 postmenopausal women who cut across multiple ethnicities, including whites, blacks, Hispanics, and Asian/Pacific Islanders. At the time of follow-up, Liu and colleagues compared 1,584 women, now diagnosed with type 2 diabetes, and matched them by age, ethnicity and other factors to 2,198 other women in the study who remained free of the disease.

While all three cytokines were found to be significantly related to an increased risk of clinical diabetes, hs-CRP appeared to be a more consistent predictor of increased risk in all four ethnic groups. These associations were independent of traditional risk factors such as obesity or elevated levels of glucose and insulin, previously reported by Liu and colleagues in the same multiethnic sample.

The pro-inflammatory state is often linked to obesity, said Liu, which can lead to insulin resistance. So, identifying these markers by a simple blood test well before a disease begins not only can help improve mechanistic understanding of the disease, but also offer alternatives to lifestylehitting an optimal balance of nutrition, for example, and engaging in more exercise - relatively simple things that can prevent disease.

Adverse housing conditions contribute to diabetes risk

Mon, 13 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) INDIANAPOLIS Fair or poor housing conditions are associated with the risk of developing diabetes in urban, middle-aged African-Americans according to a study published in the Aug. 15 issue of the American Journal of Epidemiology by a team of investigators from Indiana University School of Medicine, the Regenstrief Institute, Washington University in St. Louis and other institutions.

The researchers studied men and women in their homes (apartment or house) and environs in two St. Louis neighborhoods one a poor, inner-city area and the other a less impoverished, suburban area that included several pockets of residents from a variety of socioeconomic backgrounds. Adjusting for previously recognized diabetes risk factors such as weight, smoking, exercise, alcohol use, marital status and education, the researchers found that housing conditions influenced the risk of developing diabetes, although there was no direct association with conditions in the neighborhoods immediately outside their homes.

We found a strong link between housing and diabetes risk but its not clear exactly how housing conditions are exerting this influence, says study senior author Douglas K. Miller, M.D., Richard M. Fairbanks Professor in Aging Research at IU School of Medicine and a Regenstrief Institute research scientist. However, it is clear that it wont be possible to reduce disparities in health status among subgroups in the population and thus improve health without understanding how a persons environment can affect that persons health.

We looked at several factors to see if they could clarify why housing conditions were contributing to the development of diabetes, but none of these factors seemed to explain the relationship at all, explains Mario Schootman, Ph.D., lead author and chief of the Division of Health Behavior Research at Washington University. However, there were several potential explanations such as environmental contaminants that we were unable to measure, so additional study is clearly indicated.

Quality of housing was evaluated based on cleanliness inside of the building and the physical condition of the buildings interior and exterior, as well as the condition of the furnishings in the building. Neighborhoods were rated based on noise, air quality and the conditions of houses, streets, yards and sidewalks. Broken windows, bad siding on homes, cracks in the sidewalks and nearby industrial sites or traffic noise lowered a neighborhoods rating. Housing and neighborhood conditions were classified as fair, poor, good or excellent

This study is part of a larger health research project involving African-Americans. In the original project, researchers looked at several factors responsible for the higher incidence of health problems experienced by later middle-aged and older African-Americans living in St. Louis. That larger project gathered data from 998 African-Americans in the St. Louis area who were born between 1936 and 1950. When that project began, diabetes already was very common in this population. More than 25 percent had the disease at the time initial interviews were conducted. The new study found that over the next three years another 10 percent developed diabetes.

The rate at which this African-American population is developing new onset diabetes is extremely important as well, Dr. Miller notes. At this rate, and combined with the group who had diabetes at baseline, more than one-half of the population will be diabetic after 10 years. With all the adverse health effects of diabetes, this is a hugely important issue for middle-aged African-Americans. Although we did not have the opportunity to conduct similar research in other cities with large numbers of urban African-Americans such as New York City, Los Angeles and Atlanta, we believe it is likely that the findings would be comparable in those cities as well.

The researchers say that additional studies are needed to determine what specifically increased the risk of diabetes as a result of poor housing conditions, but many factors have already been ruled out. The current study was funded by the National Institutes of Health.

RAND finds cases of undiagnosed diabetes drop sharply

Mon, 13 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The number of men in the United States with undiagnosed diabetes has declined sharply over the past 25 years, with Hispanics and African-Americans no longer more likely than whites to unknowingly have the disease, according to a RAND Corporation study issued today.

Study author James P. Smith found that in 1999-2002 about 20 percent of American men who had diabetes did not know they had the disease, in contrast to 25 years ago when about half of the men with diabetes were undiagnosed.

Ethnic disparities among those with undiagnosed diabetes essentially disappeared during the same period, a sign that diabetes programs targeting minority groups have encouraged more people to get tested, according to the study appearing in the August edition of the Proceedings of the National Academy of Sciences.

While undiagnosed diabetes remains a significant problem, weve done an excellent job of eliminating the disproportionate amount of undiagnosed disease among African-Americans and Hispanics, said James P. Smith, the studys sole author and corporate chair of labor market and demographic studies at RAND, a nonprofit research organization.

On a less positive note, Smith found that while disparities in undiagnosed diabetes disappeared over the past 25 years, new disparities have developed based upon education levels. Less educated American males are now less likely to have their diabetes diagnosed than those men with more schooling.

If we only target disparities by race and ethnicity, we run the risk of missing other equally important health disparities that affect those least able to deal with them, Smith said.

The study also found the rate of growth of diabetes prevalence is not as high or as dramatic as often projected. Smith found that during the period studied, the proportion of men diagnosed with diabetes jumped from about 3 percent to 7 percent -- a more than doubling of the prevalence rate. However, when undiagnosed cases were considered as well, diabetes prevalence rose overall from 6 percent to 9 percent -- an increase of only 50 percent.

Diabetes is one of the major health challenges faced across the United States, but these findings suggest that the prevalence of the disease is not growing as rapidly as often claimed, Smith said.

The study examined reasons for the rising rate of diabetes over time. The three most important reasons by far were increases in excessive weight, the transmission of diabetes from parents to children as the disease spreads, and the decline in undiagnosed diabetes. In contrast, rising levels of education actually served to reduce the prevalence of the disease.

Smith examined information from several waves of the federal National Health and Nutrition Examination Surveys conducted periodically from 1976 to 2002. The survey collects information from a nationally representative sample of adults through personal interviews, physical exams and laboratory tests. Blood tests conducted as a part of the survey allow researchers to measure undiagnosed diabetes.

Among the men studied from 1999 to 2002, Smith found that 6 percent of those with a high school diploma or more education were diagnosed with diabetes, while nearly 10 percent of those who did not obtain a high school diploma were diagnosed with the disease.

Smith found that those in the lowest education group were more likely to be Latino or African-American, less likely to engage in vigorous physical exercise and more likely to be overweight or smoke cigarettes.

Even after diagnosis, people with less education had more difficulty successfully managing the complex regimes of medicines and making the lifestyle changes needed to reduce the consequences of the illness, according to the study.

Smith said one troubling finding from the study was that people who were obese were more likely to have undiagnosed diabetes, despite the fact that obesity is the second largest risk factor for the disease following family history.

It may be that since the link between obesity and diabetes has received wide attention only in recent years, it may take more time for physicians to routinely test the obese for the disease, Smith said.

Diabetes is a serious illness that occurs when the body cannot properly produce or regulate insulin, which controls the level of glucose in the blood. The disease can cause many severe problems, including heart and kidney disease, circulatory ailments and vision problems. The illness was the sixth leading cause of death in the United States in 2002.

Adverse housing conditions contribute to diabetes risk

Mon, 13 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Studying people in their homes and neighborhoods, investigators have found that poor housing conditions contribute to the risk for diabetes in urban, middle-aged African-Americans.

A team of investigators from Washington University School of Medicine in St. Louis, Indiana University School of Medicine and other institutions conducted the study. They published their findings in the Aug. 15 issue of the American Journal of Epidemiology.

We looked at several risk factors to see if they could explain why some African-Americans were more likely to develop diabetes, explains Mario Schootman, Ph.D., assistant professor of epidemiology and medicine and chief of the Division of Health Behavior Research at Washington University. And we found that housing conditions somehow contribute to the development of diabetes.

The study looked at many risk factors for diabetes including weight, smoking, exercise, alcohol use, marital status and education. But when the researchers adjusted for all of those factors, housing conditions still influenced diabetes risk.

So far we can't explain why that is, Schootman says. It could potentially be related to lead. Lead is associated with the development of diabetes, and we know that in some poorer housing conditions, there's likely to be lead exposure. But it also could be related to other, unknown environmental contaminants.

Schootman also says stress might be involved. Individuals who live in poor housing conditions may be more likely to be under stress as a function of where they live. There are known links between stress and diabetes that could help explain the increased incidence of diabetes in this population.

But a counter-argument against that would be that diabetes risk was associated with housing but not neighborhoods, he says. We would have expected that if stress was playing a role, the neighborhood conditions also would be involved.

The researchers found that although there was no direct association with neighborhood conditions, sub-standard housing more than doubled diabetes risk. The two neighborhoods studied included a poor, inner-city area and a less-impoverished, suburban area that included several pockets of residents from a variety of socioeconomic backgrounds.

Interviewers spoke to participants in their homes. They gathered data about health status, access to medical care and demographic characteristics, but they also were trained to look for certain things in neighborhoods and houses.

They rated neighborhoods based on noise, air quality and the conditions of houses, streets, yards and sidewalks. Things like broken windows, bad siding on homes, cracks in the sidewalks and nearby industrial sites or traffic noise lowered a neighborhood's rating. Houses were rated based on cleanliness inside of the building and the physical condition of the building's interior and exterior, as well as the condition of the furnishings in the building. Neighborhoods and houses then were classified as fair, poor, good or excellent. Housing included both apartments and single-family homes, and housing conditions rated as fair or poor were associated with increased risks for diabetes.

It's not clear exactly how housing conditions are exerting this influence, says senior author Douglas K. Miller, M.D., the Richard M. Fairbanks Professor in Aging Research and Regenstrief Institute research scientist at Indiana University School of Medicine. But it is clear that it won't be possible to reduce disparities in health status among subgroups in the population without understanding how a person's environment can affect that person's health.

This study grew out of a larger health study involving African-Americans. In the original study, researchers looked at several factors responsible for the higher incidence of health problems experienced by later middle-aged and older African-Americans living in St. Louis. That original study gathered data from 998 African-Americans in the St. Louis area who were born between 1936 and 1950.

When that study began, diabetes already was very common in this population. More than 25 percent had the disease at the time initial interviews were conducted. The new study found that over the next three years another 10 percent developed diabetes.

I think that's a huge finding in and of itself, Schootman says. Think about how many middle-aged African-Americans live in a place like St. Louis, and if our sample is at all representative of the larger community, you can see that the number of people with diabetes is growing very rapidly over time. I also think it's likely that we would find comparable results if we had done similar research in Detroit or Atlanta or New York City.

Schootman says more studies will be needed to determine what specifically increased the risk of diabetes as a result of poor housing conditions, but many factors have already been ruled out.

Researchers find vitamin B1 deficiency key to vascular problems for diabetic patients

Tue, 07 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at Warwick Medical School, University of Warwick, have discovered that deficiency of thiamine Vitamin B1 - may be key to a range of vascular problems for people with diabetes. They have also solved the mystery as to why thiamine deficiency in diabetes had remained hidden until now.

Diabetes is increasing in incidence in the UK and elsewhere and one of the most significant health problems associated with the condition are vascular complications: microvascular complications, such as damage to the kidney, retina and nerves in arms and legs; and macrovascular complications, such as heart disease and stroke.

The University of Warwick researchers, led by Professor Paul Thornalley, have shown conclusively that diabetic patients are thiamine deficient in blood plasma. They were also able to solve the mystery of what was happening to thiamine in diabetic patients and connect it more closely to vascular complications in diabetic patients.

In a paper entitled High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease, published in Diabetologia on 4th August, the team found that thiamine concentration in blood plasma was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients. This significant decrease had been previously masked as the conventional way of assessing levels of thiamine status was to measure the activity of an enzyme called transketolase in red blood cells. Past studies had seen normal activity of this enzyme and assumed normal levels of thiamine when in fact the normal enzyme activity was due to increased amounts of two proteins THTR-1 and RFC-1 that help transport thiamine into red blood cells. The increased levels of these proteins were a direct response to there being a deficiency of thiamine in the body.

The researchers found that the decreased availability of thiamine in vascular cells in diabetes was linked to a marker of microvascular and macrovascular complications. It likely reflects problems in endothelial cells (endothelial cells line the bodys entire circulatory system) and increased risk of atherosclerosis (chronic inflammatuion in the artery walls).

The researchers found that the decreased plasma thiamine concentration in clinical diabetes was not due to a deficiency of dietary input of thiamine. Rather it was due to a profound increased rate of removal of thiamine from the blood into the urine.

The researchers feel that important areas for future study are: confirmation of low plasma thiamine concentrations in diabetic populations of other countries independent of local diet; the evaluation of thiamine and thiamine derivatives to correct low plasma thiamine concentration in diabetes, reverse vascular dysfunction and prevent vascular complications; and investigation of the mechanism of increased removal of thiamine from the blood into the urine in diabetes.

Reducing inflammation plays key role in type 1 diabetes therapy

Tue, 31 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON -- Researchers at Beth Israel Deaconess Medical Center (BIDMC) have found that a triple combination therapy consisting of both tolerance-inducing and anti-inflammatory properties is successful in abolishing adverse autoimmunity against insulin-producing cells in a mouse model of Type 1 diabetes.

The findings, which appear in the Online Early Edition of the Proceedings of the National Academy of Sciences (PNAS) this week, offer a possible new prototype for therapies to restore normal blood glucose levels in diabetes patients and suggest a previously unrecognized role for inflammation in the disease.

Type 1 diabetes is known to develop as a consequence of autoimmune destruction of insulin-producing pancreatic beta cells, explains senior author Terry Strom, MD, Director of the Transplantation Research Center at BIDMC and Professor of Medicine at Harvard Medical School. But in addition to the long-recognized role of T-cell-dependent immune-system-mediated islet destruction, this work reveals for the first time that a form of inflammation in fat and muscle [is also acting to] prevent insulin from disposing blood glucose into tissues that require glucose.

Formerly known as juvenile-onset or insulin-dependent diabetes, Type 1 diabetes develops when the bodys immune cells attack and destroy its own pancreatic beta cells. Without beta cells, the body is unable to produce insulin, a hormone needed to convert glucose into energy. To prevent the development of serious complications, more than 21 million individuals with Type 1 diabetes primarily children and young adults must receive as many as three injections of insulin each day.

Previous attempts to treat existing Type 1 diabetes were primarily focused on restoring immune tolerance, which in healthy individuals is achieved when immune system cells turn off so as not to overreact and attack ones own cells. In individuals with Type 1 diabetes, the process of immune tolerance fails to work properly, thereby permitting the self-destruction of the bodys beta cells.

But lead author Maria Koulmanda, MSc, PhD, director of Non-Human Primate Research in BIDMCs Transplantation Research Center, wondered if there might also be a role for inflammation in the disease process.

We knew that in cases of type 2 [non-insulin dependent] diabetes, a form of inflammation in muscle and fat prevents insulin from triggering the transfer of glucose from the blood into important insulin-sensitive tissues, explains Koulmanda, who is also Assistant Professor of Surgery at HMS. We thought that in addition to autoimmune destruction of insulin-producing cells, there might also be inflammation-induced insulin resistance [in type 1 diabetes.]

To test this hypothesis, the authors administered a cocktail of three separate agents (rapamycin plus agonist IL-2- and antagonist-type, mutant IL-15-related Ig fusion proteins) in a NOD (non-obese diabetes) mouse model of type 1 diabetes. The therapy regimen, which included two novel immunoglobulin-fusion proteins, was aimed at both increasing tolerance and decreasing inflammation.

As predicted, following two to four weeks of treatment, the mice that had received the triple therapy maintained normal levels of blood sugar. In contrast, the control group of diabetic mice did not survive, despite receiving insulin.

The authors then conducted a molecular analysis which confirmed that the treatment had eliminated insulin resistance and relieved inflammation in the animals fat and muscle tissues.

Although the treatment halted the progressive loss of insulin producing cells, the restoration of normal blood glucose levels actually was the result of inflammation being ablated in fat and muscle cells, explains Strom. By blocking the inflammation, we were able to restore the animals abilities to respond to insulin.

Our findings are very promising, adds Koulmanda. Type 1 diabetes is a serious disease requiring that children and young adults take insulin two to three times a day.

And, she adds, despite this arduous therapy, insulin treatment does not prevent the occurrence of serious late-arising complications, including kidney failure, blindness and widespread cardiovascular disease.

In clinical practice, it is not currently possible to identify when and if an individual will develop type 1 diabetes, says Koulmanda. Therefore, it is urgent to identify treatments that can restore normal blood glucose levels in patients with new-onset diabetes before insulin-producing cells are totally destroyed. We hope that our findings offer new hope in the long search for a cure of type 1 diabetes.

New technique to 'see' and protect transplants successful in diabetic animal model

Sun, 29 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at Johns Hopkins have found a way to overcome a major stumbling block to developing successful insulin-cell transplants for people with type I diabetes.

Traditional transplant of the cells, accompanied by necessary immune-suppressing drugs, has had highly variable results, from well- to poorly tolerated. Part of the problem, the Hopkins researchers say, is an inability to track the cellsso-called pancreatic beta cellsonce theyre inside the body.

Now a new technique encapsulates the insulin-producing cells in magnetic capsules, using an FDA-approved iron compound with an off-label use, which can be tracked by magnetic resonance imaging (MRI). The product, tested in swine and diabetic mice, also simultaneously avoids rejection by the immune system, likely a major reason for transplant failure. The work will be published online next week in Nature Medicine.

Were really excited because we can track where we put the cells and make sure their protective housing stays intact and that the cells dont move. This could solve the mystery of why current transplantation techniques work only for so long, says one of the studys authors, Aravind Arepally, M.D., assistant professor of radiology and surgery at Hopkins.

Type I diabetesthe most common childhood sortcauses a persons immune system to destroy the pancreatic beta cells that make insulin. Without insulin, blood sugar levels can become dangerously high and lead to complications that include blindness or kidney failure. Careful monitoring of blood sugar levels paired with insulin injections can manage the condition, but transplanting healthy beta cells holds more promise for the moment-to-moment fine-tuning of insulin levels, says Arepally.

Current experimental cell transplantation techniques are done naked and blind, only lasting a short period of time, according to co-author Jeff Bulte, Ph.D., a professor of radiology and chemical and biomolecular engineering at Hopkins. The unprotected transplanted cells are vulnerable to attack by the recipients immune system, and researchers cannot see the cells to figure out why they stop making insulin after a while.

To address both of these challenges, the research team captured beta cells in tiny porous capsules made from a mixture of alginate, a gooey material made from seaweed, and Feridex, a magnetic iron-containing material visible under MRI. They then used a machine that oozes droplets of this mixture to surround and encapsulate individual islet clusters each containing about 500 to 1,000 insulin-producing beta cells. Once the cells are encapsulated, the shell hardens, creating a magnetocapsule that measures less than 1/128 of an inch across.

Theyre tiny spheres with nano-scale pores just big enough too let the good stuff out but keep the bad from getting in, says lead author Brad Barnett, medical student and Howard Hughes fellow at Hopkins. The openings in the magnetocapsule are so small that the bodys immune system sentinels cannot reach and attack the transplanted cells.

The team first transplanted magnetocapsules into the abdomens of mice engineered to develop diabetes. Blood sugar levels in the animals returned to normal within a week and stayed that way for more than two months. In contrast, more than half of untransplanted diabetic mice died, and the rest had very high blood sugar levels.

To mimic human transplantation, the researchers then implanted magnetocapsules into the livers of swine with the help of MRI fluoroscopy, special reflective screens and a computer monitor that provide real-time imaging. The liver was chosen, rather than the usual pancreatic home of beta cells, because it contains many blood vessels that can deliver insulin quickly to the rest of the body.

Getting the magnetocapsules into the right place requires hand-eye coordination normally required when playing video games, says Arepally. The team threaded a long needle-like tube into a large vein near the upper thigh and guided the tube upward, across and into a neighboring blood vessel, ending in the body of the liver.

The pigs underwent MRI and blood tests three weeks after magnetocapsule transplantation. MRI showed that the magnetocapsules remained intact in the liver, and blood tests revealed that the cells were still secreting insulin at levels considered functional in people.

We hope that our magnetocapsules will make tissue-type matching and immunosuppressive drugs problems of the past when it comes to cell-based therapies for type 1 diabetes, says Bulte.

Genetic finding sheds light on diseases causing blood vessel breakdown

Sun, 29 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Twenty-one years after they first described a fatal genetic disorder in Missouri and Arkansas families, scientists at Washington University School of Medicine in St. Louis have linked the condition to mutations in a gene known as TREX1.

The study appears online in Nature Genetics.

The identification will accelerate efforts to understand and treat retinal vasculopathy with cerebral leukodystrophy (RVCL), a rare condition that usually goes unrecognized or is misdiagnosed. In Asian and Caucasian patients with the disease, a complex and ultimately fatal barrage of primarily central nervous system symptoms begins around age 45 that includes vision loss, mini-strokes and dementia. The symptoms can also mimic a brain tumor or multiple sclerosis. After onset, RVCL is fatal in 10 years or less.

Because small blood vessels in the back of the eye and the brain disappear in patients with RVCL, the new link could have important relevance to a much broader range of health problems affecting the elderly, including common diseases like diabetes that also alter microvessels.

Why TREX1 mutations would suddenly cause these blood vessels to start disappearing at midlife is a mystery, says senior author John Atkinson, M.D., the Samuel Grant Professor of Medicine and professor of molecular microbiology. But now that we have this link, what it teaches us about the health and maintenance of these blood vessels also may help a great deal in understanding and preventing their loss in aging and in diabetes.

Also on the list of disorders linked to blood vessel loss is vascular dementia, a condition that causes memory loss, disorientation, and emotional problems in the elderly. In the United States, vascular dementia is the second-leading cause of these kinds of symptoms after Alzheimer's disease; in some Asian nations, it is the leading cause of dementia.

Gil Grand, M.D., professor of clinical ophthalmology and visual sciences at Washington University, and Atkinson led the research team that in 1986 first reported RVCL as a novel human disease. Since then, researchers have identified other families with RVCL in Europe, Australia and Taiwan.

In 2002, Atkinson's group and colleagues at other institutions tied the condition to a portion of the third chromosome. Unfortunately, the region is rich with more than 150 complex genes, and initial attempts to locate the specific gene that causes RVCL were unsuccessful.

With a grant from the Genome Sequencing Center (GSC) at Washington University, scientists recently began a new attempt. The lead researcher, Anna Richards, M.D., Ph.D., at that time a member of the Atkinson lab and now clinical lecturer in nephrology, Royal Infirmary, Edinburgh, elected to begin the search with a simple gene whose structure made it easiest to sequence.

In a stroke of good fortune, that gene, TREX1, turned out to be the gene they were looking for. In the 10 families scientists studied, they found that family members with RVCL consistently had one of five different TREX1 mutations.

A small but rapidly expanding body of scientific literature already exists on TREX1, which is an important mammalian gene. It is active in almost all cells, where it proofreads DNA for errors and helps correct those mistakes. Cells sometimes introduce such errors into DNA when they copy it prior to cell division, and environmental factors like radiation and reactive chemicals can also create errors.

According to Atkinson, though, there's little in the limited TREX1 literature to suggest why mutations in the gene should cause small blood vessels to start dying off in middle-aged RVCL patients. This implies that TREX1 may have a fundamental role in maintaining the health of small blood vessels that has previously gone unrecognized.

We're going to be working very hard to understand everything we can about TREX1 to try to give us some hints about what's happening to people with RVCL and how we can help, Atkinson says. What we learn may provide insights into why these same vessels sometimes start to die off in the elderly, leading to a variety of complications. The disease was discovered here in St. Louis, its genetic basis was identified by the GSC, and now our goal is to find a treatment.

Atkinson's lab has already identified a lead. They were able to show that two of the mutations they identified in RVCL patients create a tailless form of the TREX1 protein that can't properly anchor itself to the part of the cell where it normally does its job. Scientists are currently studying whether this dislocation could have any links to the damage that occurs in RVCL.

Some diabetes drugs may increase heart attack risk

Sat, 28 Jul 2007 12:21:00 PST

( from http://www.rxpgnews.com ) London, July 28 - Two drugs commonly prescribed to treat Type 2 diabetes double the risk of heart failure, say scientists.

Type 2 diabetes is a life-long disease marked by high levels of sugar in the blood.

It was earlier known that the drugs rosiglitazone and pioglitazone should not be used for patients known to have heart failure, but new research indicates that the drugs can provoke the problem even in those without a history of heart disease.

Researchers of University of East Anglia studied data of over 78,000 patients and estimated that one in every 50 people taking the drugs over a 26-month period would require hospitalisation because of heart failure, the online edition of BBC News reported.

The researchers also looked in detail at more than 200 cases of patients with heart failure related to the diabetes drugs and found that the problem developed even in patients taking low doses of the drugs.

'This means that the diabetes drugs could have caused thousands of additional cases of heart failure,' said lead researcher Yoon Loke.

While heart failure is often thought to be a problem affecting older patients, the researchers also found that one quarter of cases occurred in people younger than 60.

Patients are advised not to stop taking the drugs, but to consult their physicians if they have concerns, the experts said.

Older is better -- Top-10 comparison of diabetes drugs give metformin top grade

Tue, 24 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A type 2 diabetes drug taken orally and in widespread use for more than a decade has been found to have distinct advantages over nine other, mostly newer medications used to control the chronic disease, according to a study by researchers at Johns Hopkins.

In their report, published online July 16 in the journal Annals of Internal Medicine, the Hopkins team found that metformin, first approved by the U.S. Food and Drug Administration in 1995 (and sold as Glucophage, Riomet and Fortamet), not only controlled blood sugar levels but also was less likely to cause weight gain and more likely than others to lower bad cholesterol levels in the blood.

Researchers say these health benefits are important because they can potentially ward off heart disease and other life-threatening consequence from diabetes. More than 15 million Americans have type 2 diabetes.

Sometimes newer is not necessarily better, says lead study author Shari Bolen, M.D., an internist at Hopkins. Issues like blood sugar levels, weight gain and cost could be significant factors to many patients struggling to stay in good health, says Bolen, an instructor at The Johns Hopkins University School of Medicine.

In what is believed to be the largest drug comparison of its kind, the scientists showed that all of the commonly used oral medications worked much the same at lowering and controlling blood sugar levels, and were equally safe. But metformin stood out because it offered the same level of effectiveness without lowering glucose measurements too much, and it did so for a lower price.

Metformin was found to lower LDL or bad cholesterol by about 10 milligrams per deciliter of blood, while newer medications studied, such as pioglitazone (Actos) and rosiglitazone (Avandia), or so-called thiazolidinediones, were found to have the opposite effect, increasing levels of the artery-clogging fat by the same amount.

Researchers say the main drawbacks to metformin are digestive problems and diarrhea. Previous reports have found evidence that the medication leads to the buildup of lactic acid in the blood in people with moderate kidney or heart disease, and they note that it should not be prescribed to anyone with either of these conditions. The main advantages to both newer thiazolidinediones were a small increase in HDL or good cholesterol, and less too-low blood sugar levels than three other older, cheaper drugs studied -- glimepiride (Amaryl), glipizide (Glucotrol), glyburide (Micronase, DiabBeta, Glynase PresTab) -- known as second-generation sulfonylureas.

Annual treatment with metformin or the sulfonylureas, they note, costs on average $100, roughly one-fourth the cost of oral diabetes medications FDA-approved since then, including the two newer thiazolidinediones, both approved in 1999. (Their price is expected to drop once generic versions become available.)

When you are dealing with an epidemic like diabetes, it is important for people to weigh their treatment options with their physician and to make informed decisions about which medication best suits their needs, says Bolen.

In the study, Bolen and her colleagues reviewed the scientific evidence from 216 previous studies and compared each drug for its clinical effectiveness, risks and costs. In addition to metformin, the thiazolidinediones and sulfonylureas, drugs included in their analysis were repaglinide (Prandin), miglitol (Glyset), acarbose (Precose), and nateglinide (Starlix).

Among the teams other findings were that glimepiride, glipizide, and glyburide led more frequently to too-low blood sugar levels than the other drugs. The sulfonylureas and acarbose appeared to have no effect on bad cholesterol. And except for metformin and acarbose, drug treatment led to an increase in weight from 2 to 11 pounds.

Researchers also noted the increased risk of heart failure, albeit small (less than three people in a hundred), in people taking thiazolidinediones who did not have a history of heart disease. They also caution that despite recent reports about the potential for increased risk of heart attack from rosiglitazone, there is not yet sufficient information to verify the finding.

Researchers say further studies are needed to compare the long-term effectiveness of one treatment to another and to compare drug effects on quality of life and life expectancy. Additional research will also be needed to compare these findings with results for injectible medications for diabetes, most notably insulin, which was not included in the latest report.

Reducing insulin signaling in the brain can prolong lifespan

Thu, 19 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) One route to a long and healthy life may be establishing the right balance in insulin signaling between the brain and the rest of the body, according to new research from Childrens Hospital Boston. The study, published in the July 20 issue of Science, not only reinforces the value of exercising and eating in moderation, but also helps explain a paradox in longevity research.

Insulin sends a vital signal throughout the body telling cells to use sugar from the blood. But when cells become less sensitive to insulin, which often happens as we age and gain weight, the body must make more insulin to keep sugar under control and avoid type 2 diabetes. For a long time, clinicians and scientists thought that more insulin was a good thing, says Morris White, PhD, a Howard Hughes Medical Institute investigator in Childrens Division of Endocrinology, who led the new study. But the increased insulin also gets into the brain, where it can be detrimental.

Studies in the worm C. elegans and in fruit flies show that reducing insulin signaling lengthens lifespan. But in humans and rodents, reducing insulin signaling often causes diabetes. The view that insulin could reduce lifespan is difficult to reconcile with decades of clinical practice and scientific investigation to treat diabetes.

White suspected that the key to explaining this paradoxand to maximizing both health and longevityis to reduce insulin signaling only in the brain. To test this idea, Whites team measured longevity and other characteristics in several groups of mice. In one group, they used a genetic trick to cut in half the amount of Irs2, a protein that carries the insulin signal inside the cell, in every cell of the body. Two other groups of mice were genetically engineered to have half, or nearly all, Irs2 removed only from the brain cells. Another group of normal mice served as controls.

To our surprise, all of the engineered mice lived longer, says Akiko Taguchi, PhD, first author of the study. Even more surprising, the mice lacking Irs2 only in the brain lived almost half a year longer than the normal mice an 18 percent increase in lifespan despite being overweight and having higher blood insulin levels, changes that usually reduce lifespan. These long-lived mice were more active in old age, retained youthful metabolic cycles (burning sugar by day and fat by night) and retained protective levels of anti-oxidant enzymes such as superoxide dismutase, which protect against oxidative stress, or biological rusting, in the brain and body.

The mice with normal brain Irs2 levels aged less gracefully they lost the metabolic rhythms of youth, became more sedentary, and had reduced anti-oxidant enzymes after meals, leaving them vulnerable to cellular damage. Such damage correlates with a host of age-related diseases such as atherosclerosis, Alzheimers disease and cancer, notes White.

White believes the study findings suggest a new approach to preventing diseases that shorten lifespan. The engineered mice live longer because the diseases that kill them cancer, cardiovascular disease and others are being postponed by reducing insulin-like signaling in the brain, he says, regardless of how much insulin there is in the rest of the body.

Drugs that regulate Irs2 signaling in the brain (but not elsewhere in the body) are one possible preventive strategy, but no such drug has yet been found. Targeted drugs will be important because Irs2 is needed in other tissues, particularly the pancreatic beta cells that produce insulin.

The easiest way to keep insulin levels low in the brain, White says, is old-fashioned diet and exercise. Although obesity and sedentary lifestyles tune down the bodys sensitivity to insulin, exercise can bring it back and reduce blood insulin levels. Eating smaller meals keeps insulin low in the bloodstream, ensuring that less reaches the brain. The new drugs designed to fight insulin resistance and type 2 diabetes might have a similar effect.

This study provides a new explanation of why its good to exercise and not eat too much, says White. It has less to do with how we look, and more to do with a healthy brain, especially in old age.

The study also calls into question the long-term effects of insulin therapy for diabetes, White adds. High insulin should be the short term solution to insulin resistance, because it might damage the brain in the long run, he says. Better treatments for diabetes and healthy aging, he suggests, should concentrate on sensitizing the bodys cells to low amounts of insulin.

New review adds more reasons to avoid diabetes drug Avandia

Tue, 17 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Little evidence supports using rosiglitazone (Avandia) to improve the quality or length of life among adults with diabetes, according to a systematic review of data by German researchers.

Furthermore, data suggest that the drug might worsen complications of the disease such as weight gain, swelling, bone fractures and heart disease. The new review supports findings from an analysis of studies, published in May, which reported an increased risk of death from cardiovascular causes in patients taking the medication.

On May 21, the Food and Drug Administration issued a safety alert saying, Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack, should talk to their doctor about this new information.

The benefit-risk ratio of rosiglitazone therapy in type 2 diabetes mellitus needs urgent clarification, say the authors of the latest review, led by Bernd Richter, M.D., of Heinrich-Heine University. New safety data should lead to a very cautious approach to rosiglitazone use. If possible, other antidiabetic medications should be employed.

The findings are particularly alarming because heart disease accounts for nearly 70 percent of deaths among people with diabetes. Type 2 diabetes affects about 18 million to 20 million Americans, according to the American Diabetes Association.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The authors pooled data from 18 randomized controlled trials including more than 8,000 participants. About half of the patients took rosiglitazone and the others received either an alternative medication or a placebo. Most of the trials lasted about 6 months, although the longest one followed patients for four years.

All of the published studies aimed primarily to evaluate metabolic or glycemic control, which is the drugs ability to lower blood sugar levels, the review authors say. Rosiglitazone treatment produced about the same reductions as other oral antidiabetic drugs.

When the reviewers looked at patient-oriented results of the treatments such as side effects, diabetic complications or death, they found a more negative picture. The pooled data revealed that patients taking rosiglitazone gained up to 11 pounds in body weight and that the chance of developing edema (swelling) doubled. These changes indicate that the drug causes fluid retention, which can lead to shortness of breath and heart failure.

The largest single trial included in the review involved more than 4,000 patients and showed evidence of raised cardiovascular risk, as well as increased numbers of broken bones in women.

Existing treatment strategies concentrating on lowering of blood sugar alone are not sufficient due to the complex nature of the diabetic condition, Richter said. The use of proxy indicators like metabolic control is not sufficient to approve drugs that many patients have to take for the rest of their lives.

He advises patients who suffer from heart disease, especially congestive heart failure, to speak with their doctors about switching to another antidiabetic treatment. If you are a woman and especially if you are thin you probably should avoid this medication due to the risk of bone fractures, he said.

Avandia manufacturer GlaxoSmithKline takes issue with the use of meta-analyses in a May 12 statement, saying they are not the most rigorous way to reach definite conclusions about adverse events. Citing several recent and ongoing clinical trials, the company says, GSK stands firmly behind the safety of Avandia when used appropriately and we believe its significant benefits continue to outweigh any treatment risks.

Richter, however, said that even a tiny risk associated with a drug such as rosiglitazone, prescribed to millions of people, will eventually translate into grave consequences.

In view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at this time is unclear, say public health experts Bruce Psaty, M.D., and Curt Furberg, M.D., in a New England Journal of Medicine editorial published June 14. The journal published the initial analysis of Avandia.

Rosiglitazone represents a major failure of the drug-use and drug-approval processes in the United States, Psaty and Furberg write, comparing the situation to the withdrawal of the painkiller rofecoxib (Vioxx) from worldwide markets in 2004.

The Cochrane reviewers concur, saying, Current drug approval for antidiabetic medications and possibly all new drugs needs to be changed. However, they also question whether new studies with rosiglitazone will be ethical given the fact that less-dangerous therapeutic alternatives exist.

Gene discovered for type 1 diabetes in children

Sun, 15 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Pediatrics researchers at The Childrens Hospital of Philadelphia and McGill University in Montreal have identified a gene variant that raises a childs risk for type 1 diabetes, formerly called juvenile diabetes. As investigators continue to pinpoint genes contributing to diabetes, they have their eyes on providing a scientific basis for designing better treatments and preventive measures for the disease.

The research adds a new gene and new knowledge to the four genes previously discovered for type 1 diabetes, in which the immune system destroys insulin-producing beta cells in the pancreas and makes patients dependent on frequent insulin injections to keep the bodys blood sugar under control. As the project continues, the study team expects to identify additional genes (perhaps as many as 15 or 20) thought to interact with each other in the disease.

The study appeared July 15 in an advance online letter in the journal Nature.

The genotyping technology we now have available has revolutionized the way we can ask and answer research questions, said the studys lead author, Hakon Hakonarson, M.D., Ph.D., the director of the Center for Applied Genomics at The Childrens Hospital of Philadelphia. Unlike the previous technology, which was quite limited and dealt largely with relatively rare gene variants, we can now detect common genetic variants that are important in large numbers of individuals, and begin to understand how multiple genes interact in complex diseases such as diabetes.

In the discovery phase of the study, the investigators examined the genomes of 1,046 children with type 1 diabetes. These DNA samples came from patients and families followed in pediatric diabetes clinics in Philadelphia and four Canadian cities. Specifically, the researchers compared the genomes of 563 patients with type 1 diabetes with those of 1,146 matched control subjects. Those results were combined with those obtained from an independent analysis of 483 family trios, in which the genomes of a child with the disease and both parents were examined.

The researchers confirmed the four previously identified locations for genes contributing to type 1 diabetes, but also uncovered a new type 1 diabetes locus on chromosome 16, occupied by a gene called KIAA0350. The team then replicated this discovery in yet another independent cohort of 1,333 children with the disease from the Type 1 Diabetes Genetics Consortium, which includes children of European descent in Europe, North America and Australia, as well as in 390 additional type 1 diabetes family trios from Canada.

Constantin Polychronakos, M.D., director of Pediatric Endocrinology at McGill University and senior author of the study, said that better knowledge of genes that predispose to type 1 diabetes may later enable physicians to screen newborns to predict those at high risk for the disease.

The gene implicated in the current research, KIAA0350, is known to be active almost exclusively in immune cells. Although scientists do not currently know the exact function of the protein the gene encodes, other research has predicted that it produces a protein called C-type lectin that is located on the surface of immune cells and binds to groups of sugars in the body.

The role of KIAA0350 needs to be investigated, said Hakonarson. However, a special cell type called a natural killer (NK) cell expresses this gene abundantly, although at different levels based on these gene variants. Our hypothesis is that a special mutation in KIAA0350 may influence the sugar binding of the protein, and trigger an autoimmune response that activates these NK cells in such a way that they attack and destroy the islet cells in the pancreas, resulting in type 1 diabetes. A particular version of the gene protects against this inappropriate autoimmune response, while a different version of the gene makes it more likely to happen.

Although much research remains to be done, better understanding of the disease process may guide doctors to new and improved therapies. If we know the gene pathways that give rise to type 1 diabetes, we hope to intervene early in life with targeted drugs or cell therapies to prevent the disease from developing, said Polychronakos.

The current research used a technique called genome-wide association, in which highly automated analytic equipment rapidly scans each patients DNA for more than half a million genetic markers. It was performed at the Center for Applied Genomics at Childrens Hospital. The Centers tools spell out a patients genotypethe specific pattern of variations among an individuals 30,000 genes. Established in the summer of 2006, the center is taking on one of the largest genotyping projects in the world, and is the largest one dedicated to genetic analysis of childhood diseases.

This study is the first one that our center has published on a gene associated with a complex childhood disease, but we have many projects under way and several other papers in press, said Hakonarson. Our goal at the Center is to discover the major disease-causing variants and genes that influence complex pediatric diseases, thus providing a scientific foundation that is based in biology for translating those discoveries into successful treatments.

Among its current projects, the Centers investigators are focused on identifying genes involved in pediatric asthma, allergy, obesity, attention-deficit hyperactivity disorder, autism, inflammatory bowel disease, hypertension, juvenile rheumatoid arthritis and the pediatric cancer neuroblastoma. The Center recently contributed 4,000 DNA samples to an industry-hosted database that serves as a free repository of control samples for researchers seeking gene variations in diseases.

Selenium supplements may increase the risk of type 2 diabetes

Fri, 13 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- Selenium, an antioxidant included in multivitamin tablets thought to have a possible protective effect against the development of type 2 diabetes, may actually increase the risk of developing the disease, an analysis by researchers at the University at Buffalo has shown.

Results of a randomized clinical trial using 200 micrograms of selenium alone showed that 55 percent more cases of type 2 diabetes developed among participants randomized to receive selenium than in those who received a placebo pill.

Results will appear in print in the August 2007 issue of Annals of Internal Medicine and were posted online on July 10.

Self-reported diagnosis of type 2 diabetes was a secondary endpoint in a clinical trial designed to test the benefit of selenium supplementation in prevention of non-melanoma skin cancer in areas in the Eastern U.S. where selenium levels are lower than the national average. Selenium is a trace mineral that is an essential component of proteins involved in antioxidant activity.

Saverio Stranges, M.D., Ph.D., first author on the diabetes prevention study, conducted the analysis while at UB, in cooperation with colleagues from Roswell Park Cancer Institute. He now is affiliated with the Clinical Sciences Research Institute, Warwick Medical School, Coventry, UK. Stranges said the findings are very interesting, but should be considered cautiously.

Among participants taking selenium supplementation, those who had the highest levels of selenium in their circulation at the beginning of the study had the highest risk of developing type 2 diabetes over the average 7.7 years of follow-up, he said, and the increase in risk is unlikely to be a result of chance.

However, in the general population, very few people, if any, take selenium supplements only, every day, for nearly eight years, so we cant be sure that these findings apply to the public at large.

Perhaps the more important message is that a large proportion of the U.S. population, about 50 percent, takes multivitamins, even though there is no evidence that taking multivitamins helps prevent chronic disease among healthy people. In this country, we can get all the antioxidants we need in fruits and vegetables, but its easier to take a vitamin than to eat a more healthy diet.

The selenium and diabetes study involved 1,202 people who did not have type 2 diabetes when they entered the cancer clinical trial at Roswell Park. Participants had been recruited for the main study between 1983 and 1991, and they were involved for an average of 7.7 years. The supplementation study was completed in February 1996.

Analysis for this diabetes study involved data from 600 persons who had taken selenium and 602 who were randomized to receive placebo pills. Results showed that 97 participants developed type 2 diabetes during the study period, 58 in the selenium group and 39 in the placebo group. There was no difference in the findings when age, sex, smoking status and body mass index were included in the analysis.

At the moment we dont know what mechanism or mechanisms account for this finding, said Stranges. We have very little understanding of the possible biological pathways involved. In addition, our findings need to be replicated in larger clinical trials before conclusive evidence can be drawn on whether high doses of selenium supplements increase the risk of type 2 diabetes, as our study suggests.

With selenium, which is a trace element, it may be the case that a little bit is essential, but more can cause detrimental effects, at least in well-nourished populations such as the U.S. Its possible that taking extra selenium overcomes the natural balance. Perhaps excess selenium has a negative effect on the endocrine system.

Bak protein sets stressed cells on suicide path, researchers show

Thu, 12 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) When a cell is seriously stressed, say by a heart attack, stroke or cancer, a protein called Bak just may set it up for suicide, researchers have found.

In a deadly double whammy, Bak helps chop the finger-like filament shape of the cells powerhouse, or mitochondrion, into vulnerable little spheres. Another protein Bax then pokes countless holes in those spheres, spilling their pro-death contents into the cell.

We found out Bak has a distinct function in regulation of the mitochondrial morphology, says Dr. Zheng Dong, cell biologist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta and corresponding author on a paper published this week in Proceedings of the National Academy of Sciences. Bax, on the other hand, is not involved in morphological regulation but needs to be there to puncture holes.

One has to break up, kind of soften, the mitochondria for injury, and the other one actually punches the holes to kill it, says Craig Brooks, MCG graduate student and the papers first author.

Bak and Bax have similar structures and scientists have long suspected they play major, similar roles in programmed cell death, or apoptosis. These two proteins are very important for mitochondrial injury and subsequent apoptosis, says Dr. Dong.

To stress cells, they blocked oxygen supplies and used the common chemotherapeutic agent cisplatin, then documented that filamentous mitochondria became fragmented very early and quickly in apoptosis. Ironically they also found the deadly fragmentation results from Baks interaction with mitochondria-shaping proteins called mitofusins, which help mitochondria keep their filamentous shape in non-stressed cells. Dr. Dong suspects Bak may also play a role in mitofusin regulation in normal, non-stressful conditions.

In fact, the researchers suspect Bak, Bax and the contents they spill into the cell all have roles in keeping a cell functioning until a stressor kicks in.

They probably are both kept in check normally in the cell by other proteins, and when something happens that overwhelms the cell, it activates Bak and Bax to start cell death, says Mr. Brooks. Some of the same proteins, cytochrome c is the big one, are needed for daily mitochondrial function like making energy, but if they are released from the mitochondria, they activate a cell killing or apoptotic pathway, says Dr. Dhong, referencing the contents that spill from punctured mitochondria.

Looking at kidney cells and neurons in a Bak deficient mouse, they also showed that Bak and Bax need each other to successfully spawn cell suicide. If you have Bak but not Bax, the mitochondria still fragment but they dont die; if you have Bax but not Bak, you still have punctures in the mitochondria but with low efficiency, says Mr. Brooks.

Now they want to know exactly how Bak interacts with mitofusins, how the interaction is regulated and how it affects mitochondrial morphology, physiology and pathology. Their long-term goal for better understanding the cell suicide mechanism is developing drugs to block it in the case of a stroke, for example, or induce it to kill cancer.

Link between carbohydrate quality and vision loss is strengthened by new data

Wed, 11 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON -- Age-related macular degeneration (AMD) and its associated vision loss may be connected to the quality of carbohydrates an individual consumes. In a study published in the July issue of the American Journal of Clinical Nutrition, Allen Taylor, PhD, director of the Laboratory for Nutrition and Vision Research at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University, and colleagues confirmed earlier findings linking dietary glycemic index with the risk of developing AMD.

Men and women who consumed diets with a higher glycemic index than average for their gender and age-group were at greater risk of developing advanced AMD, corresponding author Taylor says. The severity of AMD increased with increasing dietary glycemic index.

Glycemic index is a scale applied to foods based on how quickly the carbohydrates in foods are converted to blood sugar, or glucose. Foods like white rice, pasta and bread are examples of foods with a high-glycemic-index, meaning that these foods are associated with a faster rise and subsequent drop in blood sugar. Whole wheat versions of rice, pasta and bread are examples of foods that have a low-glycemic-index. These foods are often considered higher quality carbohydrates because they are associated with a slower and less dramatic rise and fall of blood sugar.

Our results build upon findings from an earlier, smaller study in which we determined that consuming a diet with a high glycemic index, but not one with a high total amount of carbohydrate, increased the risk of developing early AMD, says first author Chung-Jung Chiu, DDS, PhD, scientist in the Laboratory for Nutrition and Vision Research at the HNRCA and an assistant professor at Tufts University School of Medicine.

In the current study, Taylor, Chiu, and colleagues analyzed data from 4,099 men and women participating in the nationwide Age-Related Eye Disease Study (AREDS). Detailed dietary histories were obtained at the start of the study when participants were 55 to 80 years of age and had varying degrees of AMD. The AREDS was designed to assess the effect of high-dose antioxidant vitamins and zinc on the progression of AMD and cataracts, two of the leading causes of vision loss in older adults.

Although carbohydrate quality was not the main focus in the AREDS, we were fortunate that the investigators had collected the dietary carbohydrate information we needed to do our analyses, says Taylor, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts and the Tufts University School of Medicine. Our findings suggest that 20 percent of the cases of advanced AMD might have been prevented if those individuals had consumed a diet with a glycemic index below the average for their age and gender, notes Taylor.

AMD typically occurs after middle age, although the events which cause it may begin earlier. A leading cause of irreversible blindness, AMD results from the gradual breakdown of light-sensitive cells in the central region of the eye's retina, called the macula. Although there is no effective therapy for AMD, dietary intervention may delay its progress. Identifying modifiable risk factors for AMD is becoming increasingly important as the population ages. As Taylor and colleagues point out, the number of people in the US with visually impairing AMD is expected to double and reach three million by 2020.

Our results support our hypothesis, says Taylor, that dietary glycemic index, which has been related to the risk of diabetes, is also associated with the risk and severity of AMD. Taylor speculates that carbohydrates that comprise a high-glycemic-index diet may provide eye tissueIt is possible that the type of damage produced by poor quality carbohydrates on eye tissue is similar in both diabetic eye disease and AMD.

Taylor and colleagues conclude that the risk for AMD may be diminished by improving dietary carbohydrate quality, as defined by dietary glycemic index. This may be achieved by relatively simple dietary alterations, such as replacing white bread with whole grain bread. However, Taylor cautions, additional studies are needed before we can recommend dietary carbohydrate management as a prevention strategy for AMD.

New blood test might offer early warning of deep belly fat

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Measuring levels of a chemical found in blood offers the best indicator yet of the amount of fat surrounding abdominal organs, according to a new study of lean and obese individuals reported in the July issue of Cell Metabolism, a publication of Cell Press. The buildup of such visceral fat is of particular health concern as it has been linked to insulin resistance, type 2 diabetes, and heart disease risk.

The researchers, including Barbara Kahn and Timothy Graham of Harvard Medical School and Matthias Blüher of the University of Leipzig in Germany, showed that retinol-binding protein 4 (RBP4) is produced in much greater amounts by visceral fat compared to the subcutaneous fat that lies just beneath the skin. Moreover, they report that blood serum levels of RBP4 jump in people who are obese, who have double or even triple the concentrations found in individuals of normal weight.

We believe that in the near future, measurements of RBP4 serum concentrations might serve as a novel biomarker for visceral obesity and increased risk for type 2 diabetes and other adverse outcomes of visceral obesity, said Blüher. In addition, pharmacological interventions that reduce RBP4 levels might be a new approach in the treatment of metabolic syndrome and visceral obesity.

Prior to 2005, when Kahns group showed that elevating RBP4 levels in mice causes insulin resistance and lowering them in obese mice can improve insulin sensitivity, the only known function of RBP4 was to carry vitamin A (also known as retinol) in the blood, Kahn said.

The researchers went on to show that serum RBP4 concentrations are also elevated in insulin-resistant individuals with obesity, type 2 diabetes, or impaired glucose tolerance, and even in otherwise normal people with a strong family history of diabetes. Likewise, interventions designed to improve insulin sensitivity, such as exercise training, lifestyle modification, or gastric banding surgery also lead to a decline in RBP4 levels.

Serum RBP4 concentrations in humans also correlate highly with waist-to-hip circumference ratio (an estimate of intra-abdominal fat mass), waist circumference, and percent trunk fat. Those findings suggested that the amount of visceral fat might contribute directly to blood concentrations of RBP4, although the connection had not been clearly shown, the researchers said.

In a study of 196 people, the researchers now reveal that RBP4 is indeed preferentially produced in the deep fat that covers organs of the belly. RBP4 gene expression activity levels spiked about 60-fold in the visceral fat of viscerally obese relative to lean study participants, they found. By comparison, visceral fat RBP4 concentrations were increased just 12-fold in obese individuals with a preponderance of subcutaneous fat.

We were surprised about the magnitude of RBP4 differences between obese and lean people, Blüher said.

RBP4 in the blood rose along with its gene expression activity in fat and with intra-abdominal fat mass, independently of age, gender, and body mass index. Among several fat-secreted proteins considered to be important in regulating insulin/glucose balance, serum RBP4 concentrations appear to be the best indicator of insulin resistance and intra-abdominal fat mass, the researchers concluded.

This suggests a potential role for RBP4 as a convenient marker not only for type 2 diabetes but also for cardiovascular risk, they wrote. In addition, RBP4 may provide a mechanistic link between visceral adipose tissue accumulation and the increased metabolic and cardiovascular risks associated with it. Kahn said her group is still investigating whether the effects of RBP4 depend on vitamin A or whether they are due to RBP4 protein itself.

Anti-malarial drug may reduce risk of diabetes for patients with rheumatoid arthritis

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Preliminary research suggests that use of the anti-malarial drug hydroxychloroquine may help reduce the risk of the development of diabetes in patients with rheumatoid arthritis, according to a study in the July 11 issue of JAMA.

Type 2 diabetes mellitus affects nearly 8 percent of US adults, and its prevalence has been increasing.Antimalarials such as hydroxychloroquine, a long-standing safe and inexpensive treatment for an autoimmune disease such as rheumatoid arthritis, theoretically may improve glucose tolerance and prevent diabetes mellitus, according to background information in the article. In vitro and animal studies indicate that antimalarials improve insulin secretion and peripheral insulin sensitivity.

Mary Chester M. Wasko, M.D., M.Sc., of the University of Pittsburgh, Pa., and colleagues examined the association between hydroxychloroquine therapy and risk of diabetes in patients with rheumatoid arthritis. The study included 4,905 adults with rheumatoid arthritis (1,808 had taken hydroxychloroquine and 3,097 had never taken hydroxychloroquine) with no initial diagnosis or treatment for diabetes, with 21.5 years of follow-up (Jan. 1983 through July 2004).

During the observation period, incident diagnoses of diabetes were reported by 54 patients who had taken hydroxychloroquine and by 171 patients who had never taken it. Analysis indicated that patients who had taken hydroxychloroquine had a 38 percent lower risk of developing diabetes, compared with those who had not taken hydroxychloroquine. This risk was further reduced with increased duration of hydroxychloroquine use. Patients who took hydroxychloroquine for more than four years had a 77 percent lower risk of diabetes compared with those who had never taken hydroxychloroquine.

We report herein the first evidence, to our knowledge, suggesting that use of hydroxychloroquine is associated with a reduced risk of developing diabetes in patients with rheumatoid arthritis, the authors write. Moreover, risk reduction increased with duration of hydroxychloroquine exposure, supporting a biological action of this drug on glucose metabolism.

While our study showed a reduction in diabetes incidence specifically in a rheumatoid arthritis cohort taking hydroxychloroquine, these findings also may be expected to occur in patients without rheumatoid arthritis. The beneficial changes in glucose metabolism and insulin sensitivity reported among patients with lupus, patients with type 2 diabetes, and in animal models suggest that these effects are not specific to rheumatoid arthritis.

Antimalarial drugs may have a role in treating rheumatoid arthritis not only to suppress synovitis [inflammation around the joints] but also to reduce the likelihood of developing glucose intolerance and dyslipidemia [abnormal concentrations of lipids]. As quality of life and life expectancy improve for patients with rheumatoid arthritis, and health care costs escalate, the use of inexpensive, safe therapies that have multiple beneficial effects is attractive. Further prospective studies are needed to determine whether this treatment option should be considered a standard component of rheumatoid arthritis combination therapy in the future, and to evaluate the potential role of hydroxychloroquine as a preventive agent for diabetes among high-risk individuals in the general population, the researchers conclude.

Class of medications may offer alternative option for treating type 2 diabetes

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A review of previous studies indicates that use of a class of medications known as incretin-based therapy, which act via certain pathways that affect glucose metabolism may provide modest effectiveness and favorable weight change outcomes for the treatment of type 2 diabetes and may represent an alternative to other hypoglycemic therapies, according to an article in the July 11 issue of JAMA.

Current therapies for type 2 diabetes are often limited by adverse effects such as weight gain or hypoglycemia (low blood sugar). A more recent class of treatment to address these issues is incretin therapy, which involves glucose-stimulated insulin secretion by intestinally derived peptides, which are released in the presence of glucose or nutrients in the gut, according to background information in the article. In October 2006 the Food and Drug Administration approved the first oral incretin enhancer, sitagliptin, a selective DPP4 inhibitor (a class of oral hypoglycemics), for use as monotherapy or in combination with other medications. The effectiveness of this class of medications in managing type 2 diabetes is not well understood.

Renee E. Amori, M.D., of Tufts-New England Medical Center, Boston, and colleagues conducted a meta-analysis of 29 studies to assess the effectiveness and safety of incretin-based therapy (GLP-1 analogues and DPP4 inhibitors) in nonpregnant adults with type 2 diabetes.

Our analysis of randomized controlled trials showed that incretin-based therapy with GLP-1 analogues or DPP4 inhibitors in adults with type 2 diabetes is moderately effective in improving glycemia, with greater reductions in postprandial [after a meal] glycemia and favorable (GLP-1 analogues) or neutral (DPP4 inhibitors) effects on weight. Glucagon [a hormone secreted by the pancreas]-like peptide 1 analogues were associated with gastrointestinal adverse effects, while DPP4 inhibitors had a slightly increased risk of infection (nasopharyngitis [inflammation of the nasal passages] and urinary tract infection) and headache, the authors write.

Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes with modest efficacy and a favorable weight change profile, they write. Individuals with mild diabetes, suggesting an adequate pancreatic beta cell reserve, who are at risk of hypoglycemic sequelae and in need of weight loss may benefit from this new class. However, these new classes of hypoglycemic agents will need continued evaluation both in long-term efficacy and safety controlled trials and in clinical practice to assess their effectiveness and safety profile to determine their role among the many available and well-established therapies for type 2 diabetes.

Common rheumatoid arthritis treatment shows potential for diabetes prevention

Tue, 10 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, July 10 Far fewer rheumatoid arthritis patients treated with the drug hydroxychloroquine (HCQ) went on to develop diabetes compared to those who never took the drug, according to a 20-plus-year University of Pittsburgh School of Medicine-led study reported today in the Journal of the American Medical Association. In addition, those using HCQ who did develop diabetes were less likely to take medications to manage their disease after diagnosis.

The multi-center observational study of 4,905 adults with rheumatoid arthritis (RA) found that relative risk progressively declined by as much as 77 percent after four years of treatment with HCQ, a common antimalarial medication that also is used for rheumatoid arthritis and other autoimmune disorders.

Additional participating centers in the study are Stanford University, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), one of the National Institutes of Health (NIH) and the University of Cincinnati. Co-investigators at Stanford have directed the project database since its inception with support from the NIH.

This reduction in risk persisted even after adjusting for other diabetes risk factors among these patients, such as body-mass index, degree of disability and use of corticosteroids, said rheumatologist Mary Chester M. Wasko, M.D., M.Sc., associate professor of medicine, University of Pittsburgh School of Medicine. Because people with RA tend to be less active and take corticosteroids that can cause weight gain, they are often considered to be at higher risk for developing diabetes, a disease in which blood sugar levels become abnormally high because of the bodys inability to use or produce the hormone insulin.

Another interesting finding was that the rheumatoid arthritis patients who developed diabetes were less likely to need blood sugar-lowering medication to manage their disease, said Dr. Wasko, whose clinical research has focused on long-term health improvement in patients with RA. However, it is most exciting to consider that this drug might be appropriate for people with pre-diabetes as a preventive therapy much in the same way as a daily baby aspirin is suggested for people at high risk for heart disease.

Nationally, diabetes is the fifth leading cause of death, according to the American Diabetes Association. Many people first become aware of the disease when confronted with one of its life-threatening complications such as heart disease, blindness, high blood pressure, stroke, kidney disease or circulatory problems that can lead to amputation.

Results show that HCQs association with reduction in diabetes risk is comparable or superior to that of a number of other drugs studied in clinical trials for diabetes prevention and treatment, including rosiglitazone, hormones, metformin, acarbose and ramipril. And recent questions have arisen concerning rosiglitazone, marketed as Avandia, and a reported increased risk of heart attack.

Although HCQ is not without side effects nausea, headache and dizziness, for example the drug has a long history of being generally safe and well-tolerated. In addition, Dr. Wasko and her colleagues observed no apparent negative interactions between HCQ and other drugs commonly used by RA patients, such as methotrexate and prednisone. An important limitation of the study, however, is that investigators used self-report information from patients collected in follow-up twice yearly that did not include confirmation by laboratory tests.

Other studies of the blood sugar-lowering effects of HCQ have shown minimal use for the drug as a treatment for people with established diabetes, Dr. Wasko continued, stressing the treatments real promise may be prevention.

HCQ already has a role in long-term treatment for RA, potentially moderating lipids and having a weak anti-clotting effect. But, optimistically speaking, endocrinologists can identify people who are at high risk for diabetes, due to obesity, family history, lipid profile or other characteristics. HCQ may also have a role in delaying onset of diabetes, Dr. Wasko said. More research is needed to verify our findings in people with RA, and also to determine how this medicine works. But my ultimate hope is that this relatively inexpensive, safe drug will be studied as a way to reduce diabetes risk for people who do not have RA.

Protein's role in lipid absorption may be important to future weight-loss strategies

Thu, 05 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) July 5, 2007 -- Researchers at Washington University School of Medicine in St. Louis have found that a protein absorbs lipids in the upper part of the intestine, and they believe its key role in this process may provide a novel approach for obesity treatment in the future.

Principal investigator Nada A. Abumrad, Ph.D., the Dr. Robert C. Atkins Professor of Medicine and Obesity Research at Washington University School of Medicine, first identified the protein, CD36, that facilitates the uptake of fatty acids. The protein is located on the surface of cells and distributed in many tissues, including fat cells, the digestive tract, heart tissue and skeletal muscle tissue.

Her studies have shown that the intestine makes large amounts of CD36, and that it is important to the absorption of fatty acids. Initially when she compared normal mice that made the protein to genetically altered mice lacking CD36, she couldn't find any net difference in their fat absorption.

But the new study, reported in the July 6 issue of the Journal of Biological Chemistry, reveals the reason it was not possible to identify a difference. Apparently, the intestine has some built-in redundancy.

Normally, CD36 absorbs fatty acids in the upper, or proximal part of the intestine, but when it is absent, lower, more distal, sections of the intestine compensate and absorb the fat.

We think of the intestine as a single organ, but it's really made up of distinct areas that are so specialized it's almost like several organs, Abumrad says. The fat that is not absorbed in the proximal areas ends up being bumped into the distal intestine where different systems absorb it,

Abumrad and her colleagues, including first author Fatiha Nassir, Ph.D., research assistant professor in the Division of Gerontology and Nutritional Science, believe that targeting the upper part of the intestine and interfering with normal CD36 function might be a useful tool in weight loss. The team found that animals that could not make CD36 absorbed fat less efficiently, and as a result they tended to eat less of it.

And the most exciting part for us right now is the fact that these things may apply to humans, Abumrad says. Humans with mutations in the gene that makes CD36 don't seem to process fat normally either.

She learned from the mice that when fatty acids and cholesterol are not absorbed in the proximal part of the intestine, as normally occurs, the distal intestine packages those fats very differently.

The proximal intestine makes molecular packages called chylomicrons, she says. These bundles that contain lipids and proteins transport these molecules from the intestine to other parts of the body. CD36, which is abundant in the proximal intestine, turns out to play a role both in absorbing fatty acids and cholesterol and in packaging these lipids into chylomicron bundles that facilitate their use throughout the body.

When no CD36 was present in the genetically altered mice in Abumrad's study, the lipids were absorbed more slowly since they had to travel to lower, more distal parts of the intestine. And they also were packaged differently. Rather than being bundled into chylomicrons, the lipids were released as parts of smaller particles that are not as easily absorbed by other tissues as the chylomicrons.

For years, Abumrad has studied how CD36 modulates the acute and chronic responses of muscle and fat cells to energy fluctuations and other stresses. Her goal is to translate her findings from rodents into humans, where variations in the CD36 gene are common.

There is evidence that people have different amounts of CD36 and that mutations in the gene are quite common, she says. Those variations are associated with abnormalities of blood lipids, with high levels of fatty acids in the blood, abnormal blood triglycerides and increased risk of diabetes-associated heart disease. It's clear that some of us have different amounts of this protein in different tissues, and some individuals don't have any of it.

Although scientists in Abumrad's laboratory think it may be possible eventually to help people lose weight by interfering with the CD36 protein, they first want to learn more from the mouse. Currently, they work with mice that cannot make CD36 anywhere in their bodies. But because the protein also operates in heart tissue and skeletal muscle, disabling CD36 everywhere can have detrimental effects. So the team is working to develop a new kind of mutant mouse, one that can make CD36 everywhere except in the intestine.

If we find that such a mouse still has delayed absorption of fatty acids and cholesterol and ends up eating less fat, we'll have more evidence that this might be a good approach to use in humans, she says. Block the function of the protein in the intestine, absorb fewer lipids, and since your absorption is delayed, you don't feel as hungry and you eat less.

But until such a mouse is developed, Abumrad's team cannot be certain that blocking the effects of CD36 in the intestine might not also have harmful effects. Interfering with CD36 function to absorb less fat is not necessarily a good thing if it causes problems in the heart, the liver or elsewhere in the body.

Chemical in brain acts like a fuel gauge

Thu, 05 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The concept that a drop in blood sugar triggers a craving for food is best understood just before lunchtime.

But exactly how the process unfolds has proven difficult to explain, even on a full stomach.

Solving the puzzle would yield new insights in the fight against diabetes. Neuroscientists at the University of Southern California provide a partial answer in the July 4 issue of The Journal of Neuroscience.

Their study, highlighted by the journal on its news page, identifies a chemical that sends a low blood sugar message to a part of the brain that can do something about it.

The neurotransmitter norepinephrine travels from the hindbrain, which receives warnings of low glucose levels from the body, to the paraventricular hypothalamus, which authorizes the consumption of energy stores to replace the missing sugars.

The energy stores help for a while, but the end result is a feeling that the body is running on empty. Lunch, anyone

While the study has few near-term clinical implications, except perhaps for diabetics with low blood sugar (hypoglycemia) from insulin overdoses, it is of fundamental interest in the field.

Theres a huge interest in how the body senses glucose, said Alan Watts, director of the Neuroscience Research Institute at USC and a co-author of the study.

How that information is processed by the brain is really a hot current topic.

Knowing how neurons relay hypoglycemia warnings is critical to understanding the overall glucose sensing mechanism in the brain, added corresponding author Arshad Khan, a research assistant professor at USC.

Thats why Im interested in this system, because its very poorly understood, Khan said.

If we dont know how an automobiles fuel system works to begin with, then how can we expect to fix one when it is not burning fuel appropriately

In his study, Khan injected insulin in a group of animals to drop their blood sugar levels. In another group, he injected norepinephrine directly into the paraventricular nucleus.

Khan then compared brain tissue sections from both groups of animals and also examined blood samples for the presence of hormones released by paraventricular nucleus activity.

The same paraventricular neurons lit up in both sets of animals, and the animals displayed similar increases in hormone levels, suggesting that norepinephrine plays a role in transmitting the hypoglycemia warning.

Norepinephrine is capable of activating these signals just like hypoglycemia does, Khan said.

Khan then confirmed his findings with analogous experiments in vitro carried out in collaboration with neuroscientists at the University of California, Riverside.

Additional results from an ongoing study suggest that norepinephrine is not only sufficient but necessary for conveying hypoglycemia signals from the hindbrain, Khan added.

The current study, funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, was inspired by earlier work published in the journal Endocrinology by Sue Ritter of Washington State University.

In her studies, one of which was co-authored by Watts, Ritter showed that hypoglycemic animals lost their feeding and hormonal responses to hypoglycemia after damage to the norepinephrine pathways connecting the hindbrain to the hypothalamus.

Early indicator of kidney disease may also predict risk of pre-diabetes

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BUFFALO, N.Y. -- A blood component called cystatin C, used to test for early-stage kidney impairment, also may be a very early marker for those at risk of developing a condition known as pre-diabetes, a study conducted by researchers at the University at Buffalo has shown. Pre-diabetes is diagnosed when the amount of glucose in the bloodstream begins to rise and remain above normal, an indication that glucose is not being absorbed properly by cells.

An estimated 54 million people Americans have been diagnosed with pre-diabetes, which, if not arrested, often develops into full-blown Type 2 diabetes, a serious chronic disease linked to heart disease, stroke, kidney failure, blindness and nerve damage.

UB researchers report in the July 2007 issue of Diabetes Care that high levels of cystatin C were associated with a three-fold risk of progression to pre-diabetes in their study population.

Its important to identify people at risk of pre-diabetes very early, because you can prevent this condition from developing by making changes in diet and lifestyle, said Richard P. Donahue, Ph.D., first author on the study.

If further studies support our finding, testing for cystatin C could become an important part of a standard physical examination. Preventive measures could be in place before glucose intolerance has a chance to develop and take its toll.

Donahue is an associate professor of social and preventive medicine in the UB School of Public Health and Health Professions.

The cystatin C investigation is based on the Western New York Health Study, conducted between 1996 and 2001, in which researchers collected baseline information on a number of health indicators, including fasting glucose, in a randomly selected cohort of healthy Erie and Niagara county residents.

The first follow-up to the baseline study took place between 2001 and 2004 and involved 1,455 of the original participants, all of whom had no known heart or kidney disease. Information on health indicators were collected once again. Analysis determined that 91 people who had normal glucose levels in 1996 had developed pre-diabetes since then.

Levels of cystatin C then were measured in the blood samples taken at baseline of these 91 and were compared to cystatin C levels in samples from 273 participants from the original cohort who had not developed pre-diabetes.

Results showed a direct link between those with the highest levels of cystatin C and the development of pre-diabetes, said Donahue. The association didnt change when factors that traditionally are related to development of diabetes such as weight, amount of blood glucose at baseline, smoking history, high blood pressure or alcohol use were considered, he noted.

Pre-clinical signs of renal impairment may occur before or coincident with pre-diabetes, Donahue said. These findings may suggest that those who have pre-diabetes also should be screened for early signs of kidney impairment, which itself is a major chronic illness and cause of much morbidity and mortality.

It's not too late to change -- lowering cardiac risk later in life

Thu, 28 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Can adopting a healthier lifestyle later in life help -- or is it too late? In a study published in the July 2007 issue of The American Journal of Medicine, researchers from the Medical University of South Carolina, Charleston found that people 45 to 64 years of age who added healthy lifestyle behaviors could substantially reduce their risk for cardiovascular disease (CVD) and reduce their death rate. Once these people achieved 4 healthy behaviors, eating at least 5 fruits and vegetables daily, exercising at least 2.5 hours per week, maintaining their Body Mass Index (BMI) between 18.5 and 30 kg/m, and not smoking, investigators saw a 35% reduction in CVD incidence and a 40% reduction in mortality compared to people with less healthy lifestyles.

Writing in the study, Dana E. King, MD, MS, states, The potential public health benefit from adopting a healthier lifestyle in middle age is substantial. The current study demonstrated that adopting four modest healthy habits considerably lowers the risk of cardiovascular disease and mortality in relatively short-term 4-year follow up period. The findings emphasize that making the necessary changes to adhere to a healthy lifestyle is extremely worthwhile, and that middle-age is not too late to act.

Starting in 1987 to 1989, 15,792 men and women ages 45 to 64 years participated in the Atherosclerosis Risk in Communities Study (ARIC) in four communities across the United States. This was designed to investigate the origin and progression of various atherosclerotic diseases. Follow up visits every three years through the end of 1998 included an interval medical history, weight, height, diet questionnaire, updated smoking history and current participation in sports and leisure exercise.

There were three key findings from the study first, the benefit of switching to a healthy lifestyle past age 45 became evident even in the 4-year, short-term follow up; second, the beneficial impact of the changes occurred despite the relatively modest changes in health habits; and third, the healthy lifestyle was beneficial when compared to all persons with three or fewer healthy habits, not just in comparison to people with none or one habit. People adopting only three healthy habits experienced lower mortality but not fewer CVD events over the same period.

The authors found that only 8.5% of middle-aged adults practice these four behaviors and only 8.4% newly adopt such a lifestyle past age 45. Further, men, African-Americans, and individuals with less than college education, lower income, or a history of hypertension or diabetes are less likely to adopt a healthy lifestyle past age 45, and are therefore at greater risk of mortality and cardiovascular disease.