RxPG News : Endocrinology

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.

Stress hormone, depression trigger obesity in girls

Tue, 23 Feb 2010 04:59:36 PST

( from http://www.rxpgnews.com ) Depression raises stress hormone levels in adolescent boys and girls but may lead to obesity only in girls, according to researchers. Early treatment of depression could help reduce stress and control obesity -- a major health issue.

This is the first time cortisol reactivity has been identified as a mediator between depressed mood and obesity in girls, said Elizabeth J. Susman, the Jean Phillips Shibley professor of biobehavioral health at Penn State. We really haven't seen this connection in kids before, but it tells us that there are biological risk factors that are similar for obesity and depression.

Cortisol, a hormone, regulates various metabolic functions in the body and is released as a reaction to stress. Researchers have long known that depression and cortisol are related to obesity, but they had not figured out the exact biological mechanism.

Although it is not clear why high cortisol reactions translate into obesity only for girls, scientists believe it may be due to physiological and behavioral differences -- estrogen release and stress eating in girls -- in the way the two genders cope with anxiety.

The implications are to start treating depression early because we know that depression, cortisol and obesity are related in adults, said Susman.

If depression were to be treated earlier, she noted, it could help reduce the level of cortisol, and thereby help reduce obesity.

We know stress is a critical factor in many mental and physical health problems, said Susman. We are putting together the biology of stress, emotions and a clinical disorder to better understand a major public health problem.

Susman and her colleagues Lorah D. Dorn, professor of pediatrics, Cincinnati Children's Hospital Medical Center, and Samantha Dockray, postdoctoral fellow, University College London, used a child behavior checklist to assess 111 boys and girls ages 8 to 13 for symptoms of depression. Next they measured the children's obesity and the level of cortisol in their saliva before and after various stress tests.

We had the children tell a story, make up a story, and do a mental arithmetic test, said Susman. The children were also told that judges would evaluate the test results with those of other children.

Statistical analyses of the data suggest that depression is associated with spikes in cortisol levels for boys and girls after the stress tests, but higher cortisol reactions to stress are associated with obesity only in girls. The team reported its findings in a recent issue of the

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."

Study confirms that calcium and vitamin D together help prevent fractures

Fri, 15 Jan 2010 09:22:27 PST

( from http://www.rxpgnews.com ) Taking both calcium and vitamin D supplements on a daily basis reduces the risk of bone fractures, regardless of whether a person is young or old, male or female, or has had fractures in the past, a large study of nearly 70,000 patients from throughout the United States and Europe has found.

The study included data published in 2006 from clinical trials conducted at UC Davis in Sacramento as part of the Women’s Health Initiative (WHI). It appears online in this week’s edition of the British Medical Journal.

“What is important about this very large study is that goes a long way toward resolving conflicting evidence about the role of vitamin D, either alone or in combination with calcium, in reducing fractures,” said John Robbins, professor of internal medicine at UC Davis and a co-author of the journal article. “Our WHI research in Sacramento included more than 1,000 healthy, postmenopausal women and concluded that taking calcium and vitamin D together helped them preserve bone health and prevent fractures. This latest analysis, because it incorporates so many more people, really confirms our earlier conclusions.”

Led by researchers at Copenhagen University in Denmark, Robbins and an international team of colleagues analyzed the results of seven large clinical trials from around the world to assess the effectiveness of vitamin D alone or with calcium in reducing fractures among people averaging 70 years or older. The researchers could not identify any significant effects for people who only take vitamin D supplements.

Among the clinical trial results analyzed was Robbins’ WHI research, which was part of a 15-year, national program to address the most common causes of death, disability and poor quality of life in postmenopausal women such as cardiovascular disease, cancer and osteoporosis. Those trials were primarily designed to study the effect of calcium and vitamin D supplementation in preventing hip fractures, with a secondary objective of testing the supplements on spine and other types of fractures, as well as on colorectal cancer. The results were published in the Feb. 16, 2006 edition of the New England Journal of Medicine.

Fractures are a major cause of disability, loss of independence and death for older people. The injuries are often the result of osteoporosis, or porous bone, a disease characterized by low bone mass and bone fragility. The National Osteoporosis Foundation estimates that about 10 million Americans have osteoporosis; 80 percent of them are women. Four of 10 women over age 50 will experience a fracture of the hip, spine or wrist in their lifetime, and osteoporosis-related fractures were responsible for an estimated $19 billion in health-related costs in 2005.

“This study supports a growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing a variety of fractures,” said Robbins. “Interestingly, this combination of supplements benefits both women and men of all ages, which is not something we fully expected to find. We now need to investigate the best dosage, duration and optimal way for people to take it.”

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.

NIEHS awards Recovery Act funds to address bisphenol A research gaps

Wed, 28 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) For Immediate ReleaseWednesday, October 28, 2009

Contact:Robin Mackar, NIEHS(919) 541-0073

NIEHS Awards Recovery Act Funds to Address Bisph

Researchers studying the health effects of the chemical bisphenol A (BPA) gathered in North Carolina to launch an integrated research initiative to produce data that will allow for a comprehensive assessment of its possible human health effects.

Researchers who just received funds from the American Recovery and Reinvestment Act to study BPA were brought together to meet with scientists from academia and government already working on the compound. The meeting was held Oct. 6, 2009 at the National Institute of Environmental Health Sciences (NIEHS).

The meeting is part of an effort to support human and animal research that will help determine if current exposures to BPA in the general population pose a potential health risk. NIEHS is part of the National Institutes of Health (NIH) and has the lead in supporting research to study the potential effects that chemicals, such as BPA, may have on human health. President Obama allocated $5 billion in Recovery Act funds to the NIH, with about $14 million going to NIEHS for research on BPA.

We know that many people are concerned about bisphenol A and we want to support the best science we can to provide the answers, said Linda Birnbaum, Ph.D., who serves as director of the NIEHS and the National Toxicology Program (NTP), an interagency program for the U.S. Department of Health and Human Services. Bringing the key BPA researchers together at the onset of new funding will maximize the impact of our expanded research effort.

NIEHS will invest approximately $30 million over two years on BPA-related research. This includes existing grants, the newly awarded Recovery Act grants and supplements, in-house research and NTP projects. The NTP effort is part of a larger five-year commitment to collaborate with the U.S. Food and Drug Administration's National Center for Toxicological Research to examine long-term health outcomes resulting from developmental exposures.

BPA is a chemical used primarily in the production of polycarbonate plastics and epoxy resins. People, including children, are exposed to BPA in food and beverages when it leaches from the internal epoxy resin coatings of canned foods and also from consumer products such as polycarbonate tableware, food storage containers, water bottles and baby bottles. In 2008, NTP and NIEHS concluded that there is evidence from animal studies that BPA may be causing adverse effects. But researchers are uncertain about whether the changes seen in the animal studies would result in human health problems. For this reason, NIEHS identified BPA as a priority area.

The innovative two-year grants provided through the Recovery Act will support human and animal studies that address many of the research gaps identified by expert scientific panels, and provide a better understanding of how this chemical may impact human health.

We want the new grantees to be able to hit the ground running, said Jerry Heindel, health scientist administrator at the NIEHS who oversees much of the institute's portfolio on BPA. Having the key players talking to one another as they begin new research efforts will stimulate collaboration, create opportunities to share resources, and encourage researchers to develop reliable and reproducible methods that will allow for a comprehensive assessment of the human health effects of BPA.

In animal studies, there is some evidence linking BPA exposure with infertility, weight gain, behavioral changes, early onset puberty, prostate and mammary gland cancer and diabetes. For the newly funded research, two-year animal and human studies will focus on either developmental exposure or adult chronic exposures to low doses of BPA. Researchers will be looking at a number of health effects including behavior, obesity, diabetes, reproductive disorders, development of prostate, breast and uterine cancer, asthma, cardiovascular diseases and transgenerational or epigenetic effects. The 10 Recovery Act NIH Grand Opportunities grants focusing on BPA research have been awarded to:

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.

UGA geneticist receives $2 million federal stimulus grant for research on the thymus

Thu, 17 Sep 2009 03:59:36 PST

( from http://www.rxpgnews.com ) The National Institutes of Health have awarded, as part of the American Reinvestment and Recovery Act, a two-year, $2 million grant to a University of Georgia genetics researcher and her colleagues for studies on the thymus, the organ in humans that produces disease-fighting T-cells.

Nancy Manley, a professor of genetics and chair of UGA's Interdepartmental Biology Group, is the principal investigator on the grant, which will support studies on molecular mechanisms regulating thymic epithelial cells during aging. The new grant supports a collaborative program between UGA, the University of Texas M. D. Anderson Cancer Research Center in Science Park, Tex., and the Center for Stem Cell Research at the University of Edinburgh in Scotland.

Other principal investigators are Ellen Richie, professor of carcinogenesis (Texas) and Clare Blackburn, group leader (Edinburgh).

This research is an excellent example of how the stimulus money is providing jobs in science and, at the same time, helping unravel new findings that could be important for human health, said Manley.

The grant will allow Manley to hire two research scientists, a laboratory technician and a full-time administrator.

While research on the thymus may seem arcane, it is, in fact, the subject of intense interest and extends and expands work in which Manley has been involved for some years now.

Last year, Manley's lab, using the mouse as a biological model, provided the first evidence that a key gene may be crucial to maintaining the production of the thymus and its disease-fighting T-cells after an animal's birth.

The discovery could help scientists find out how to turn the thymus back on so it could produce T-cells long after it normally shuts down most of its function, which, for humans, occurs by early adulthood. If the finding leads to further ways to manipulate the gene, the result could be a new avenue for the body to fight disease more effectively as it ages.

Such things as infectious diseases, inflammation and heart problems are all related to immune response, Manley said last year. You don't have to think far to see how understanding the effect of this gene could affect the quality of life for older people and others as well.

The newly funded research will try to discover the actual mechanisms by which the thymus shuts down and how these changes affect immune system function during aging. If and when that mechanism is found, scientists may find a way to turn the organ's function back on permanently or at specific times in the life of a human or an animal to fight disease or aging. An ultimate payoff might be longer and healthier lives for people.

The thymus is an organ located in the upper part of the human chest cavity, behind the sternum. This organ is the location where important systemic infection fighters called T-cells develop. Over the past two decades, T-cell counts have become part of everyday dialogue due to their importance in monitoring HIV/AIDS and other disorders.

The thymus slowly begins to shut down early in life and becomes largely inactive by early adulthood. Still, that's fine for most people, since an entire lifetime supply of T-cells is produced in that time. But, for some people, the loss of irreplaceable T-cells through disease can lead to chronic illnesses and a shortened life.

Until recently, scientists had thought that the thymus after birth was unable to regenerate T-cells because no known regulatory mechanism existed that might allow doctors to turn back on the thymus if a person's T-cells were compromised. There are now, however, some treatments currently in trials that can transiently rejuvenate the thymus and increase thymic output in humans.

The problem has been, though, that the mechanisms by which all this works are poorly understood, and all current treatments have systemic effects that can cause unacceptable side effects in all but the most seriously ill, who are more willing to tolerate them in exchange for possible benefit.

So far, the possibility of this working looks very good, said Manley.

While the mouse model doesn't precisely mimic human response, it is close enough so that biologists and geneticists can often draw conclusions from mouse trials on how humans will respond.

Though the ability of science to manipulate this gene and potentially the production of T-cells isn't going to happen next week, it may not be that far down the road, either. Under best circumstances, the researchers should know within five to 10 years whether the therapeutic ability to turn back on the production of T-cells is possible.

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."

Fat in the liver -- not the belly -- is a better marker for disease risk

Mon, 24 Aug 2009 03:59:36 PST

( from http://www.rxpgnews.com ) New findings from nutrition researchers at Washington University School of Medicine in St. Louis suggest that it's not whether body fat is stored in the belly that affects metabolic risk factors for diabetes, high blood triglycerides and cardiovascular disease, but whether it collects in the liver.

Having too much liver fat is known as nonalcoholic fatty liver disease. The researchers report online in the journal PNAS Early Edition that when fat collects in the liver, people experience serious metabolic problems such as insulin resistance, which affects the body's ability to metabolize sugar. They also have increases in production of fat particles in the liver that are secreted into the bloodstream and increase the level of triglycerides.

For years, scientists have noted that where individuals carried body fat influences their metabolic and cardiovascular risk. Increased fat inside the belly, known as visceral fat, is associated with an increased risk of diabetes and heart disease.

Data from a large number of studies shows that visceral fat is associated with metabolic risk, which has led to the belief that visceral fat might even cause metabolic dysfunction, says senior investigator Samuel Klein, M.D. However, visceral fat tracks closely with liver fat. We have found that excess fat in the liver, not visceral fat, is a key marker of metabolic dysfunction. Visceral fat might simply be an innocent bystander that is associated with liver fat.

Klein, the Danforth Professor of Medicine and Nutritional Science, directs the Division of Geriatrics and Nutritional Science and the Center for Applied Research Studies, as well as Washington University's Center for Human Nutrition. He says most of our body fat, called subcutaneous fat, is located under our skin, but about 10 percent is present inside the belly, while much smaller amounts are found inside organs such as the liver and muscle.

This study compared obese people with elevated and normal amounts of liver fat. All subjects were matched by age, sex, body mass index, percent body fat and degree of obesity. Through careful evaluations of obese people with different amounts of visceral fat or liver fat, Klein's team determined that excess fat inside the liver identifies those individuals who are at risk for metabolic problems.

We don't know exactly why some fats, particularly triglycerides, will accumulate inside the liver and muscle in some people but not in others, says first author Elisa Fabbrini, M.D., Ph.D., assistant professor of medicine. But our data suggest that a protein called CD36, which controls the transport of fatty acids from the bloodstream into different tissues, is involved.

Fatty acids are the building blocks for making fats, known as triglycerides. Klein, Fabbrini and their colleagues found that CD36 levels were lower in fat tissue and higher in muscle tissue among people with elevated liver fat.

Fabbrini and Klein say changes in CD36 activity could be responsible for diverting circulating fatty acids away from fat tissue and into liver and muscle tissue, where they are converted to triglyceride. Increased tissue uptake of fatty acids could be responsible for metabolic dysfunction.

Klein says those who are obese but don't have high levels of fat in the liver should be encouraged to lose weight, but those with elevated liver fat are at particularly high risk for heart disease and diabetes. He says they need to be treated aggressively to help them lose weight because dropping pounds can make a big difference.

Fatty liver disease is completely reversible, he says. If you lose a small amount of weight, you can markedly reduce the fat content in your liver. In fact, even two days of calorie restriction can cause a large reduction in liver fat and improvement in liver insulin sensitivity.

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.

Blocking a muscle growth-limiting hormone protects against obesity and atherosclerosis

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Knockout of myostatin, a growth factor that limits muscle growth, can decrease body fat and promote resistance against developing atherosclerosis, or hardening of the arteries, according to a new study conducted in mice. The results will be presented Thursday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Obesity increases the risk of atherosclerosis, which accounts for 75% of all cardiovascular events, such as heart attacks and strokes, said study co-author Shalender Bhasin, MD, professor of medicine at Boston University School of Medicine and chief of the Section of Endocrinology, Diabetes, and Nutrition at Boston Medical Center. Current strategies aimed at preventing heart disease consist primarily of lowering cholesterol levels, but patients reaching the desired cholesterol levels are still at risk for atherosclerosis if they have other risk factors, such as obesity.

Humans and animals with a mutation in the myostatin gene are extremely muscular and have little fat, past research shows. Also, when the gene encoding myostatin is knocked out in mice, their muscle mass increases.

Bhasin and his co-workers wanted to find out if inhibiting myostatin in mice could resist the development of diet-induced obesity and of atherosclerosis, the buildup of lipid deposits called plaque that can narrow and clog coronary arteries.

The researchers took mice that were genetically altered to develop atherosclerosis and then cross-bred them with myostatin knockout mice. Ten generations later, they had mice who were genetically predisposed to both atherosclerosis and inactivation of myostatin. For controls, they studied mice with a genetic predisposition for atherosclerosis but with intact myostatin gene. All mice received a high-fat diet for 12 weeks, to spur the development of atherosclerosis.

Compared with controls, the mice with deleted myostatin gene had much less body fat and 30 percent lower fasting blood sugar and 80% lower fasting insulin levels, showing a reduction in obesity and a strong resistance to developing diabetes, the authors reported. They also had 50 percent lower low-density-lipoprotein (bad) cholesterol and 30 to 60 percent lower levels of total cholesterol and triglycerides (fats in the blood), respectively. These results indicate protection against the development of atherosclerosis, according to Bhasin.

More research is needed to demonstrate the safety and effectiveness of myostatin inhibitors in humans, Bhasin said. However, he said that that this therapeutic strategy already is possible. Experimental drugs called myostatin blockers or inhibitors are being studied as potential treatments of muscle wasting disorders and limb injuries.

Some currently available nutritional supplements are touted as myostatin inhibitors, but Bhasin said he doubts they are effective.

Childhood obesity increases early signs of cardiovascular disease

Thu, 11 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) By as early as 7 years of age, being obese may raise a child's future risk of heart disease and stroke, even without the presence of other cardiovascular risk factors such as high blood pressure, a new study found. The results were presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

The study, conducted by researchers at Nemours Children's Clinic and Dr. Charles DelGiorno, an Endocrine trainee from the Mayo Clinic of Jacksonville, Fla., demonstrates that the unhealthy consequences of excess body fat start very early, said Principal investigator and senior author Nelly Mauras, MD, Chief of Pediatric Endocrinology at Nemours Children's Clinic in Jacksonville, Florida. Obesity alone, the study shows, is linked to certain abnormalities in the blood that can predispose individuals to developing cardiovascular disease early in adulthood.

Our study finding suggests that we need more aggressive interventions for weight control in obese children, even those who do not have the co-morbidities of the metabolic syndrome, Mauras said.

The metabolic syndrome is a cluster of risk factors that raise the risk of developing heart disease, stroke and diabetes. It is increasingly being diagnosed in children as overweight becomes a greater problem. Although debate exists as to its exact definition, to receive a diagnosis of metabolic syndrome, in general you must have at least three of the following: increased waist circumference (abdominal fat), low HDL (good) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood glucose (blood sugar).

Mauras and colleagues wanted to know if simple obesity could raise cardiovascular disease risk before the metabolic syndrome develops. They therefore screened more than 300 individuals ages 7 to 18 years and included just those without features of the metabolic syndrome. They included 202 subjects in the study: 115 obese children and 87 lean children as controls ~ half were prepubertal and half in late puberty. Obese children had a body mass index (a measure of body fat) above the 95th percentile for their sex, age and height.

To be eligible to participate in the study, the children and adolescents had to have normal fasting blood sugar levels, normal blood pressure and normal cholesterol and triglycerides. Lean controls also could not have a close relative with type 2 diabetes, high cholesterol, high blood pressure or obesity. The latter group proved very difficult to find.

All study participants underwent blood testing for known markers for predicting the development of cardiovascular disease. These included elevated levels of C-reactive protein (CRP), a marker of inflammation, and abnormally high fibrinogen, a clotting factor, among others. Obese children had a 10 fold higher CRP and significantly higher fibrinogen concentrations, compared with age- and sex-matched lean children, the authors reported. These abnormalities occurred in obese children as young as 7-year-olds, long before the onset of puberty.

The results were striking Mauras stated, as the children were entirely healthy otherwise. Although it is not yet known whether early therapeutic interventions can reverse high CRP and fibrinogen, she said it would be prudent for health care providers to advise more aggressive interventions to limit calories and increase activity in healthy overweight children, even before the onset of puberty.

Doctors often do not treat obesity in children now unless they have other features of the metabolic syndrome, she said. This practice should be reconsidered. Further studies by the growup will offer further insight into the effects of therapeutic interventions in these children.

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.

Postpartum anxiety delays puberty in offspring

Wed, 10 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Hormonal changes early in pregnancy cause maternal postpartum anxiety and behavior changes that can lead to a delayed onset of puberty in both birth and adoptive daughters, according to a new study conducted in mice. The results will be presented Wednesday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

Women have an increased rate of anxiety during pregnancy and for 2 years after giving birth, said the study's lead author, Caroline Larsen, PhD, a postdoctoral fellow at the University of Otago in Dunedin, New Zealand.

Postpartum anxiety disorders are poorly understood and difficult to treat, Larsen said. There is growing evidence that untreated anxiety disorder during pregnancy may contribute to premature birth and also can have major and lasting adverse effects on the infant's development and behavior.

Prolactin is a hormone that may protect against anxiety. Recently Larsen and her co-workers found that mice with induced low levels of prolactin in early pregnancy displayed substantial anxiety after they gave birth. Because the researchers also noted that daughters of the anxious mothers had delayed onset of puberty, they conducted the current study to learn what causes this late physical transition to sexual maturation.

Daughters of female mice made anxious by low prolactin were raised either by their birth mother or by a mouse who was not anxious (control mother). Another group consisted of daughters of nonanxious mice, and these mice were raised by either a control mother or an anxious mother. There were at least six mice in each of the four groups. The researchers determined onset of puberty by examining when the vagina opened and noting the time of first estrus (equivalent to the first menstrual cycle in humans).

Remarkably, puberty was still delayed even if the daughters of anxious mothers were raised by nonanxious mice, Larsen said. And delayed puberty also occurred in daughters born to nonanxious mothers who were raised by anxious mothers.

This result demonstrates that hormonal changes in early pregnancy, as well as changes in maternal behavior caused by these hormone changes, can alter brain development in the offspring and delay puberty, she explained. Larsen believes that their work, with further study, may translate to people.

Finding the hormonal mechanisms that trigger the timing of puberty in mice may help identify potential targets for the prevention and treatment of delayed or early puberty in humans, she said.

Late puberty in humans is linked to shortened height and psychological problems that can persist into adulthood.

Our exposure to controversial chemical may be greater than dose considered safe

Wed, 10 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) People are likely being exposed to the commonly used chemical bisphenol A (BPA) at levels much higher than the recommended safe daily dose, according to a new study in monkeys. The results will be presented Thursday at The Endocrine Society's 91st Annual Meeting in Washington, D.C.

BPA is now known to be a potent estrogen, said Frederick vom Saal, PhD, a co-author of the new study and a professor of biological sciences at the University of Missouri-Columbia. Human and animal studies indicate it could be related to diabetes, heart disease, liver abnormalities, miscarriage and other reproductive abnormalities, as well as prostate and breast cancer.

The U.S. Food and Drug Administration (FDA) declared BPA is safe based on estimates that people consume only small amounts each day from food. However, recent research indicated that U.S. adults are exposed to more BPA from multiple sources than previously thought, vom Saal said.

BPA is found in polycarbonate plastic food and beverage containers, such as water and infant bottles, as well as in the epoxy resin lining of cans and other sources. The chemical can leach into food and beverages, according to the National Institutes of Health, which funded the study by vom Saal and colleagues.

Between 8 and 9 billion pounds of BPA are used in products every year, vom Saal said.

In their study, he and his colleagues fed five female adult monkeys an oral dose of BPA (400 micrograms per kilogram of body weight). This amount is more than 400 times higher than the amount that the U.S. Food and Drug Administration (FDA) estimates that human adults are exposed to and 8 times higher than the estimated safe daily amount to consume, according to vom Saal.

Yet the blood levels of biologically active BPA over the next 24 hours were lower in the monkeys than the average levels found in people in the United States and other developed countries, vom Saal said. For levels to be higher in people when measured, their exposure dose must be greater than that given to the monkeys, he explained.

These results suggest that the average person is likely exposed to a daily dose of BPA that far exceeds the current estimated safe daily intake dose, vom Saal said.

He said that BPA exposure must come from many unknown sources, in addition to food and beverage containers. Like drugs, BPA acts in pulses, with each exposure creating a high-level pulse before it is cleared in the urine, according to vom Saal.

The researchers are continuing the study in more monkeys, but vom Saal said they do not expect to get different findings because the data in the first five animals were very consistent. The species of monkey that they used (rhesus) metabolizes BPA similar to humans, he added.

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.

Humanin peptide linked to neuronal cell survival and regulation of glucose metabolism

Wed, 22 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Recent studies have shown that the mitochondrial peptide Humanin (HN) protects against neuronal cell death such as happens in Alzheimer's disease. Now, in a study presented April 22 at Experimental Biology 2009 in New Orleans, Dr. Nir Barzilai reports that a small infusion of HN is the most potent regulator of insulin metabolism that his research team has ever seen, significantly improving overall insulin sensitivity and sharply decreasing the glucose levels of diabetic rats.

The finding is the first evidence of a role for HN in glucose metabolism and provides new insight into how this metabolism may be involved in the development of seemingly diverse age-related diseases such as Type 2 Diabetes Mellitus and Alzheimer's. The finding also provides support for the growing understanding that the brain (not just the pancreas, liver and other peripheral organs) is heavily involved in glucose metabolism.

Furthermore, says Dr. Barzilai, the Ingeborg and Ira Leon Rennert Chair of Aging Research and Director of the Institute for Aging Research at the Albert Einstein College of Medicine, the power of HN on insulin action suggests a new therapeutic approach to diabetes. Further understanding of how HN interactions with the growth hormone/insulin-like growth factor system may also lead to strategies to protect against age-related diseases including Alzheimer's.

Dr. Barzilai's presentation at Experimental Biology 2009 is part of the scientific program of the American Society for Biochemistry and Molecular Biology.

Dr. Barzilai is internationally known as a leading discoverer of longevity genes, especially those he has identified in a well-established group of almost 500 Ashkenazi Jews, aged 95 to 112, and their families. Last year, he reported that some of the oldest in this group have mutations in the gene for insulin-like growth factor 1 (IGF-1) receptor, genetic alterations that have been shown to prolong life span in worms and some mammals. In this Experimental Biology presentation, he reports that, while the production of HN generally decreases as people age, it decreases less in the centenarians and is the highest in their offspring. Studies are now underway at the Institute for Aging Research to determine if the centenarians have a mutation in the HN gene in the mitochondria.

How do these genes fit together? Although there is still much to learn, says Dr. Barzilai, his team increasingly understands how HN interacts with the GH/IGF system. In earlier studies, the team found that insulin-like growth factor binding protein-3 (IGFBP-3) binds Humanin and tempers its effects on promotion of cell survival.

In this new study, the effects of HN on insulin action also were found to be tempered by IGFBP-3. Inhibiting IGFBP-3 allowed the peptide to exert a more potent effect. That suggests a drug target, says Dr. Barzilai.

He says that in this preclinical testing period, it is still too soon to know how HN would perform in humans, but he believes the naturally occurring peptide's ability to preserve cells is promising. One concern of anti-diabetic drugs is increased risk for cardiovascular disease. When Dr. Barzilai's team administered Humanin to rats before or after they were induced to have heart attacks, however, the area of infarction (area of dead cells caused by lack of blood) actually decreased by almost 50 percent, compared to that in rats not given the peptide.

Evidence mounts that short or poor sleep can lead to increased eating and risk of diabetes

Tue, 21 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Laboratory and epidemiological studies continue to show that sleep curtailment and/or decreased sleep quality can disturb neuroendocrine control of appetite, leading to overeating, and can decrease insulin and/or increase insulin resistance, both steps on the road to Type 2 diabetes.

On April 22, at the Experimental Biology 2009 meeting in New Orleans, a panel of leading sleep researchers describes recent and new studies in this fast growing field. The session is part of the scientific program of the American Association of Anatomists (AAA).

Short sleep, poor sleep: novel risk factors for obesity and for type 2 diabetes.

Dr. Eve Van Cauter, University of Chicago, is a specialist in the effect of circadian rhythms on the endocrine system and has conducted several studies in which short-term sleep restriction damaged the body's ability to regulate eating by lowering levels of leptin, the hormone that tells the body when it has had enough. In the AAA symposium, Dr. Van Cauter describes other recently published studies from her group, one showing that only three days sleep disruption is sufficient to increase insulin resistance in humans (thus causing the body to need higher levels of insulin) and a large epidemiological study showing that short sleep over a five year period causes an increase in systolic blood pressure.

Dr. Van Cauter also describes work in other laboratories, such as a multi-center study, headed by Dr. Sanjay Patel, Case Western Reserve Medical School, in which thousands of older patients wore wrist monitors 24 hours a day, allowing researchers to objectively document how long and well they slept instead of relying on self reports. Some scientists and clinicians had believed that the relationship of short/poor sleep and obesity was important in children and adults but waned with age. Dr. Van Cauter says this study found that short/poor sleep was associated with obesity regardless of age.

Energy metabolism during chronic sleep deprivation: sleep less, eat more, don't gain weight, yet show signs of progression toward diabetes.

Panel member Dr. Michael Koban, Morgan State University, reports a new study in which sleep restriction in rats led to glucose intolerance, a prediabetic state in which the blood glucose remains higher than normal after glucose challenge. Significantly, this is the first rodent study of sleep deprivation in which there was no association between glucose dysregulation and weight gain.

For 13 days, the rats were kept awake 20 of every 24 hours, then returned to their cages where they could sleep. As in a number of other studies of sleep deprivation or poor sleep in humans and rats, the sleep restricted rats greatly increased their consumption of food, in this case a human food supplement laced with chocolate, which rats love and which allowed for a more precise measure of consumption than rat chow, which often gets strewn around like bird seed in a feeder. Control rats allowed to sleep as much as they wanted also had access to the same treat, but ate less.

Significantly, while the sleep-deprived rats ate substantially more than well-rested rats, they did not gain weight. This was due, says Dr. Koban, to an increase in energy metabolism. The resting metabolism of the sleep-deprived rats rose sharply, coupled with rapid mobilization of hepatic and muscle glycogen followed by reduction in abdominal white adipose tissue.

Further studies are now underway in the Koban laboratory that more closely mimics chronic sleep deprivation in humans. The researchers believe that extending sleep restriction will produce more pronounced glucose intolerance in which glucose levels do not return to normal levels for a longer period, thus providing more evidence that not sleeping enough could lead to diabetes in humans. The researchers also are looking for mechanisms to explain the change in metabolism related to sleep deprivation and the dissociation between weight gain and glucose dysregulation and insulin resistance.

Embargoed news from Annals of Internal Medicine

Mon, 20 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) EARLY RELEASE ARTICLE: Article available online April 21 (in print June 2)

1. Patient-Tailored Treatment Regimens May Have a More Positive Impact than Strict Glycemic Control in Managing Type 2 Diabetes

Physicians routinely emphasize tight glycemic control for patients with type 2 diabetes. However, tight glycemic control may require highly complex treatment regimens that can result in frustration, non adherence, and financial stress for some patients. Researchers reviewed large trials in which type 2 diabetic patients were randomly assigned to either tight or loose targets for glycemic control. Based on the evidence, the researchers developed practical suggestions for managing these patients. According to the authors, physicians should support healthy lifestyles, preventive care, and cardiovascular risk reduction in patients with type 2 diabetes. Physicians should individualize drug treatment approaches so that patients can aim for a blood glucose level that best balances the burden of medication with the benefit in reducing symptoms and complications of diabetes. The authors advocate for tools and tactics that encourage patient involvement in treatment decisions, as these may lead to treatment programs that are both evidence-based and consistent with patients' lifestyles and informed values.

2. Universal Insurance Coverage May Reduce Race-based Health Care Disparities

Does access to health insurance reduce race-based health care disparities? To find out, researchers studied National Health and Nutrition Examination Survey data collected from 1998 to 2006 on more than 9,000 adults with chronic conditions such as hypertension, diabetes, or coronary heart disease. The authors assessed changes over time in chronic disease control as measured by blood pressure, hemoglobin A1c, and LDL cholesterol. These measures were then compared by race, ethnicity, and education. Finally, the authors compared sociodemographic differences above and below the age of eligibility for Medicare. The researchers found that while control of hypertension, diabetes, and coronary heart disease improved over the years, gaps in disease control between white and nonwhite patients did not change. However, the gaps narrowed after age 65 when Medicare insurance begins. The authors conclude that universal health insurance could reduce disparities in care among patients from different racial or ethnic groups.

3. The USPSTF Reaffirms its Recommendations on Physician Counseling and Interventions to Prevent Tobacco Use

Smoking increases risks for heart disease, lung disease, and cancer. In pregnant women, smoking also increases the risk for miscarriage, low birthweight, and premature delivery. Quitting smoking reduces these risks. Primary care physicians have a unique opportunity to counsel adult patients about preventive healthcare, including quitting smoking. In 2003, the USPSTF concluded that the benefits of smoking cessation interventions by primary care physicians outweighed the risks. Following a review of published research since then, the USPSTF reaffirms its 2003 recommendation on counseling to prevent tobacco use. Clinicians should ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products. For pregnant women, clinicians should ask about tobacco use and provide pregnancy-tailored counseling for those who smoke.

4. Considering Genetic and Other Risk Factors May Help Identify Patients at Highest Risk for Type 2 Diabetes

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.

Obesity gene associated with susceptibility to polycystic ovary syndrome

Mon, 16 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers have shown that a gene implicated in the development of obesity is also associated with susceptibility to polycystic ovary syndrome (PCOS). The FTO gene has recently been shown to influence a person's predisposition to obesity, and is now the first gene to be associated convincingly with susceptibility to PCOS(1). Carried out by Dr Tom Barber and colleagues from the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Imperial College London, this research is the first evidence to show a genetic link between obesity and PCOS. The results are being presented at the annual Society for Endocrinology BES meeting in Harrogate.

PCOS is a common condition affecting up to 1 in 10 women of child-bearing age. PCOS affects the ovaries and is characterised by irregular periods, excessive hair growth and is a common cause of infertility. PCOS is strongly associated with obesity, and it is thought that the prevalence of PCOS will increase with rising levels of obesity. The FTO gene is known to influence weight. There are two versions of this gene, one of which is associated with increased weight gain and susceptibility to development of obesity(2).

Dr Tom Barber and colleagues are interested in working out the genetic causes of PCOS and its metabolic consequences. Given the association between PCOS and obesity, they investigated whether variants of the FTO gene also influence susceptibility to PCOS. To this end, they analysed the type of FTO gene carried by 463 PCOS patients and 1336 female population controls. They found that the type of FTO gene a person carried significantly influenced their susceptibility to PCOS. In fact, the version of the gene which is associated with increased weight gain is also associated with PCOS. The data suggest that FTO variants influence PCOS-susceptibility via an effect on fat mass. This is the first gene to be associated convincingly with susceptibility to PCOS and provides genetic evidence to corroborate the well established link between PCOS and obesity.

Researcher Dr Tom Barber said:

Polycystic ovary syndrome is an incredibly common condition affecting 1 in 10 women of reproductive age and is a leading cause of infertility. It is a genetic condition and one that is strongly associated with obesity; it is therefore of huge relevance for women given today's obesity epidemic. Our research shows that a variant of the FTO gene that has previously been shown to be associated with obesity also influences susceptibility to polycystic ovary syndrome. These data provide the first genetic evidence to corroborate the well documented association between these two conditions. Our future work will focus on elucidating the underlying mechanisms of polycystic ovary syndrome and its metabolic consequences with the hope of understanding how this common condition develops. This in turn will instruct future therapeutic developments for women who suffer from polycystic ovary syndrome.

Hormone offers promise as fertility treatment

Mon, 16 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) New research suggests the hormone kisspeptin shows promise as a potential new treatment for infertility. The research is being presented at the annual Society for Endocrinology BES meeting in Harrogate. Scientists led by Dr Waljit Dhillo from Imperial College London, have shown that giving kisspeptin to women with infertility can activate the release of sex hormones which control the menstrual cycle. This research could lead to a new fertility therapy for women with low sex hormone levels.

Kisspeptin is a product of the KISS-1 gene and is a key regulator of reproductive function. Animals and humans lacking kisspeptin function do not go through puberty and remain sexually immature. In a previous study, Dr Waljit Dhillo and colleagues showed that kisspeptin treatment leads to the production of sex hormones in fertile women; they have now extended their research to look at the effects of kisspeptin in women whose periods have stopped due to a hormone imbalance.

In this study, funded by the Medical Research Council, The Wellcome Trust and National Institute for Health Research, a group of ten women who were not menstruating and infertile, were injected with either kisspeptin (n=5) or saline (control, n=5). Blood samples were then taken to measure their levels of luteinising hormone (LH) and follicle stimulating hormone (FSH), two sex hormones essential for ovulation and fertility. Kisspeptin led to a 48-fold increase in LH and 16-fold increase in FSH, when compared to the control treatment.

This is the first study to show that kisspeptin can stimulate sex hormones in women with infertility and presents kisspeptin as a potential new therapy for human infertility.

Researcher Dr Waljit Dhillo from the Department of Investigative Medicine at Imperial College London said:

Infertility is a devastating condition that affects millions of couples worldwide. This research shows that kisspeptin offers huge promise as a treatment for infertility. From our previous results, we know that kisspeptin can stimulate release of reproductive hormones in healthy women. We have now extended this research to show that kisspeptin treatment has the same effect in women with infertility. In fact, our current data show that kisspeptin causes a greater increase in luteinising hormone production in non-menstruating women, than that in fertile women in the previous study. This is a very exciting result and suggests that kisspeptin treatment could restore reproductive function in women with low sex hormone levels. Our future research will focus on determining the best protocol for repeated kisspeptin administration with the hope of developing a new therapy for infertility.

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.

$4.8M NIH grant aids interstitial cystitis research

Fri, 26 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) University of Iowa researchers are ready to find the causes of interstitial cystitis, thanks to a five-year, $4.8 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health. The grant is the largest ever received by the University of Iowa Department of Urology.

Interstitial cystitis is a painful bladder condition that causes excessively frequent urination and associated pain. An estimated 1.3 million Americans have the condition, more than one million of them women, according to an NIH report published in 2007.

Some people with interstitial cystitis can't work because their symptoms are so severe. The condition has been difficult to treat because we don't know the causes, said the grant's principal investigator Karl Kreder, M.D., professor of urology at the University of Iowa Carver College of Medicine.

This NIH grant will allow us to explore inflammatory factors in the bladder and, as some recent evidence suggests, whether interstitial cystitis is a total body condition, said Kreder, who also is director of urodynamics, female and reconstructive urology in the Department of Urology at University of Iowa Hospitals and Clinics.

The funding makes the UI a Discovery Site for the NIH's Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network. In particular, the UI researchers will explore the roles of the pituitary gland and sympathetic nervous system in the inflammatory process. Kreder said the project involves five different, but interrelated, projects and will draw on the UI's Institute for Clinical and Translational Science.

One project, led by Susan Lutgendorf, Ph.D., professor of psychology in the UI College of Liberal Arts and Sciences, examines the hypothalamic pituitary-adrenal axis, which helps regulate temperature, the immune system, mood, sexuality, and energy, as well as reactions to stress and injury.

A second project examining brain pathways that may govern painful syndromes is led by Satish Rao, M.D., Ph.D., UI professor of internal medicine.

Catherine Bradley, M.D., UI associate professor of obstetrics and gynecology, leads a third project that is focused on the epidemiology of interstitial cystitis and categorizes it by pain mapping.

The research is rounded out by two basic sciences projects -- one to develop animal models that mimic the disorder, led by Yi Luo, Ph.D., UI assistant professor of urology, and one, led by Michael O'Donnell, M.D., UI professor of urology, that examines how certain bladder factors may predispose a person to interstitial cystitis.

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.

Better understanding of blood vessel constrictor needed to harness its power for patients

Thu, 18 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) To harness endothelin-1's power to constrict blood vessels and help patients manage high blood pressure or heart failure, scientists must learn more about how endothelin functions naturally and in disease states, says a Medical College of Georgia researcher.

Despite strong laboratory evidence that blocking endothelin-1 receptors would be an effective, targeted therapy for these two major health problems, the drugs failed patients, says Dr. Adviye Ergul, physiologist in the MCG Schools of Medicine and Graduate Studies.

These endothelin-1 receptors are logical targets for drugs to treat hypertension because of their key role in vasoconstriction, but the targets are moving and we don't know how one target plays off another, says Dr. Ergul, who discussed novel aspects of endothelin receptor interaction during the 62nd High Blood Pressure Research Conference and Workshop in Atlanta.

The current thinking in pharmacology is one hormone, one receptor equals boom: the effect. I think cells are much smarter, she says. This week, Dr. Ergul challenged colleagues across the country to consider emerging evidence that usual receptor communication is likely more complex than they thought and that disease may significantly alter communication.

Endothelin-1 receptors are known to interact: one way blood vessels keep a healthy tone, for example, is that a and b receptors on smooth muscle cells prompt constriction while b receptors on the lining of blood vessels work with nitric oxide to promote relaxation. Endothelin-1 receptors on the kidneys are a player as well, helping wring out excess water and salt. There is a delicate balance, says Dr. Ergul.

But there's apparently more to the relationships. She holds up a handful of recent journal articles which reflect mounting evidence that receptors actively work as teams of two or more. That teamwork could change their function. New technology enables scientists to literally watch receptors move closer together on a cell surface, clearly indicating that something is going on.

Numerous drugs have been developed that are antagonists that can block these receptors with the idea they can be used in hypertension and heart failure. In animal models, they worked well, she says. But in clinical trials they failed badly; a drug for heart failure actually worsened problems such as labored breathing and swelling in patients already having difficulty moving blood through their body.

The first antagonists blocked both known receptors: a and b; the next generation blocked one or the other but still didn't work. A notable exception is endothelin-1 antagonists that reduce excessive pressure and tissue buildup inside the blood vessels of patients with pulmonary hypertension. In addition to constricting blood vessels, endothelin-1 can help blood vessels grow bigger but too much can result in protein deposits that stiffen blood vessel walls.

Scientists have been scratching their heads over why blocking these receptors hasn't panned out; they've even looked for an atypical receptor that might explain it. But Dr. Ergul, an expert on endothelin-1's role in diabetes, believes the unexpected results are better explained by poorly understood relationships in normal and disease states. How receptors dimerize, how they get closer together on the cell surface, likely needs to affect our drug design, she says.

Fraternal Order of Eagles pledges to raise $25 million for UI diabetes research

Tue, 16 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Leaders of the Fraternal Order of Eagles, the University of Iowa and the UI Foundation today announced a $25 million gift commitment from the Eagles that will fund diabetes research at the UI.

In recognition of the generosity of the Eagles' international membership, the UI will establish the Fraternal Order of Eagles Diabetes Research Center in the new UI Institute for Biomedical Discovery (UIIBD).

We are thrilled by this extraordinary commitment from the Fraternal Order of Eagles, said Sally Mason, president of the University of Iowa. This partnership demonstrates our shared desire to understand and ultimately cure diabetes by moving research findings into the clinical setting as quickly as possible. We are grateful for the Eagles' vote of confidence in our research enterprise, and we pledge to meet and even exceed their expectations in the years ahead.

The UI-Fraternal Order of Eagles partnership is unique in that it represents the first time the University has joined forces with the nearly one-million-member philanthropic organization. In addition to its strengths in diabetes research, the UI brings to the collaboration the facilities of its new Institute for Biomedical Discovery, so that the Fraternal Order of Eagles' philanthropy can be devoted entirely to programmatic support of pioneering research.

We are at a pivotal moment in history when there is great promise for making very real progress in treating and preventing diabetes, said Jean Robillard, M.D., UI vice president for medical affairs. This visionary gift from the Fraternal Order of Eagles has enormous potential for helping us find a cure for this devastating disease.

The Fraternal Order of Eagles gift will fund endowed chairs and fellowships for diabetes researchers, provide seed research grants for innovative research ideas, and help recruit leading scientists in diabetes research and translational medicine. Construction of the UIIBD is being funded by a combination of state appropriations, UI resources and private gifts.

Bill Loffer, membership director and immediate past chairman of the Fraternal Order of Eagles board of trustees, said the UI combines a passion for helping people affected by diabetes with leading-edge research skill.

This partnership between the University of Iowa and the Fraternal Order of Eagles is not only something we should do, it's something we must do to find a cure for diabetes. This disease affects a significant percentage of our members as well as the population at large, Loffer said.

Diabetes is a public health crisis, according to the World Health Organization. An estimated 24 million Americans have the disorder, which means the disease has reached epidemic proportions.

We have strong programs already in place, so we are ideally positioned to use this gift to make an impact on this disease, said Paul Rothman, M.D., dean of the UI Roy J. and Lucille A. Carver College of Medicine.

Diabetes affects people of all ages. Pediatricians say the number of children with diabetes is growing at an alarming rate.

Michael Artman, M.D., physician-in-chief at UI Children's Hospital, said, We would like to have a world where no child faces a lifetime of diabetes, and with the Fraternal Order of Eagles collaboration and the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa, we can begin to do that.

UI specialists say the gift, combined with a team approach, will foster more rapid advances against the disorder. They add that this partnership provides the support that the best and brightest minds need to reach their goal of a better life for people affected by diabetes.

John Stokes, M.D., professor in the UI Department of Internal Medicine and director of its nephrology division, not only specializes in treating and studying diabetes, he is also a member of the Fraternal Order of Eagles.

I can't help but be proud of the Fraternal Order of Eagles, and I'm proud to be an Eagle. I can't think of any better partnership to exemplify what the Eagles stand for -- people helping people, Stokes said.

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.

JDRF announces 2008 Scholar Award recipients

Fri, 01 Aug 2008 03:59:37 PST

( from http://www.rxpgnews.com ) August 1, 2008, New York, NY - JDRF said today that it has recognized the work of two top diabetes researchers who are focused on accelerating the pace of science in understanding the autoimmune attack that causes type 1 diabetes, and on preventing or reversing the severe complications of this chronic and life-threatening disease.

The recipients of the third annual Scholar Award are Dr. Jeffrey A. Bluestone, Director of the Diabetes Center at the University of California in San Francisco and Dr. Mark E. Cooper, Director of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia. The most prestigious distinction offered by JDRF, the Scholar Award provides recipients with $250,000 annually for up to five years for their specialized research.

The Scholar Award is granted to individual scientists with a track record of conducting pioneering, creative research and a commitment to conducting transformative research to finding a cure for diabetes and its complications.

We are thrilled to name Dr. Bluestone and Dr. Cooper as recipients of JDRF's Scholar Award. They both exhibit a unique creative vision and approach to research that will accelerate the JDRF mission, said Dr. Richard Insel, Executive Vice President of Research for JDRF. We depend on the creativity and excellence of our scientists to continue to accelerate the pace of research leading to a cure.

Dr. Bluestone, who has a long-term commitment to the field of autoimmunity and immune intolerance, received the award for his project, Role of MicroRNAs in T cell function in Type 1 diabetes. The Scholar Award will allow Dr. Bluestone to explore the function of MicroRNA in regulatory T cells, which are critical for the prevention and control of autoimmune diabetes. MicroRNAs are small RNA molecules that can change gene expression by controlling whether certain proteins can be produced or not.

JDRF funds research to study the genetic and environmental factors that may play a role in causing diabetes, with the goal of developing tools that predict susceptibility to the disease and therapies that slow, reverse, or prevent it altogether. Dr. Bluestone's project will advance knowledge in autoimmunity and accelerate the pace of research JDRF promotes. Steady progress in autoimmunity research will eventually lead to approaches to kill off the majority of the cells that contribute to the cause of type 1 diabetes.

Dr. Cooper received the award for his research project: Set 7: a novel target for diabetic vascular complications. He plans to study the metabolic memory of cells remembering past glucose levels and in turn, damaging and destroying cells and blood vessels in people with diabetes. He will also investigate the connection between long-term high glucose and diabetic vascular complications through a new mechanism that invokes oxidative stress leading to alterations in gene expression, the penultimate driver of diabetic complications. Central to the new mechanism is the specialized enzyme called Set7, responsible for altering the fine structure of the DNA-protein complexes in our cells. Through their ability to modify the protein component of the complexes, enzymes like Set7 can change whether or not genes are expressed.

Rapidly emerging technologies and a new understanding of why and how complications develop are helping reduce the risk and severity of complications for people with type 1 diabetes. With new methods for detecting complications in their earliest stages and effective strategies for intervention, it is now possible to significantly slow down or delay the most serious consequences of diabetes related complications. Dr. Cooper's project examines diabetic cardiovascular complications and his research will enable people with diabetes to live longer, healthier lives.

Current JDRF Scholars Include:

Dr. Michael Brownlee

Inheritance of hormonal disorder marked by excessive insulin in daughters

Mon, 28 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Elevated levels of insulin could be an early sign that girls whose mothers suffer from polycystic ovary syndrome -- or PCOS -- may also be susceptible to the disease, according to gynecologists who have found evidence of insulin resistance in young children.

The findings could help determine whether daughters of women suffering from PCOS are at a higher risk of developing the disease, compared to girls whose mothers do not have the disease.

Polycystic ovary syndrome is a common hormonal disorder that affects women of reproductive age, and sometimes causes inability to become pregnant. Symptoms include hairiness due to excessive amounts of male hormones, irregular periods, and insulin resistance.

We found insulin resistance in children who had entered puberty, and whose mothers had PCOS, said Richard Legro, M.D., professor of obstetrics and gynecology, Penn State College of Medicine and lead author. We did not find it in the youngest children, which suggests that the disease is triggered by puberty.

Legro and his colleagues were interested in finding out whether metabolic and reproductive abnormalities associated with the inheritable disease, are more likely to show up in children whose mothers have PCOS, and how parents could find out whether their child was at risk.

The researchers designed a study to compare 38 children -- boys and girls aged 4 to 14 -- whose mothers had PCOS with 32 children in a control group. They specifically looked for the early onset of androgen -- male hormones -- production, and production of excess insulin.

We collected samples of saliva and urine to analyze levels of insulin and sex steroids respectively, explained Legro. But we also looked for gonadotropins, hormones that stimulate sex steroids and provide the earliest sign of puberty.

Results from the test indicate that older girls, but not boys, of PCOS mothers had significantly higher concentrations of salivary insulin. Compared to the control group, the girls also had lower levels of urinary hormones.

According to Legro, the key finding of the study is that insulin levels appear to be elevated in daughters of PCOS mothers, which becomes more pronounced as they pass through puberty. Since the androgen levels were comparatively normal throughout puberty, and insulin resistance was only found in girls who had undergone puberty, Legro argues that insulin is the primary problem, while male hormones are a secondary problem.

Insulin is the real culprit in terms of stimulating the ovary, more so than gonadotropins, said Legro, whose findings appeared in a recent issue of

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."

Minimally-invasive weight loss surgery improves health and morbidly obese teens

Wed, 18 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (June 18, 2008) -- Teenagers' obesity-related medical complications improve just six months after laparoscopic gastric banding surgery, according to outcomes data presented this week. The preliminary results by physician-scientists from Morgan Stanley Children's Hospital of NewYork-Presbyterian and Columbia University Medical Center were presented on June 17 at The Endocrine Society's 90th Annual Meeting in San Francisco.

The study reports that the small group of extremely obese teenagers who received the minimally invasive surgery, also called the Lap-Band procedure, as part of a clinical trial lost an average of 20 pounds after six months and had significant improvements in abdominal fat, triglyceride measurements (levels of fat in the blood) and blood sugar levels as measured by hemoglobin A1c -- all risk factors for diabetes and heart disease. The patients' liver function and a measure of immune response also improved, according to the abstract.

Extremely obese teenagers have obesity-related health problems, particularly diabetes and increased cardiovascular risk. Laparoscopic gastric banding, which has been shown to be a safe and effective way to lose weight, now offers the possibility of reducing obesity's medical complications, says lead author Dr. Ilene Fennoy, a pediatric endocrinologist at Morgan Stanley Children's Hospital of NewYork-Presbyterian and clinical professor of pediatrics at the Columbia University College of Physicians and Surgeons. Until recently, these patients have had to rely primarily on non-surgical methods or higher-risk surgeries to lose weight, and few of these treatments have succeeded in achieving major weight loss or greatly improving their overall health.

The Lap-Band procedure, which is approved by the Food and Drug Administration (FDA) for adults but not yet in teenagers, involves making the stomach smaller without staples. Instead, a band is place around the upper part of the stomach, creating a small pouch that restricts food intake. The surgeon implants a small access port, and after the surgery the doctor periodically adjusts the gastric band by inflating or deflating a saline-filled balloon that lies inside the band. If desired, the procedure is reversible. Morgan Stanley Children's Hospital/Columbia University Medical Center is one of three sites in the nation approved to study this procedure in teens.

The study, which is part of the multidisciplinary FDA-approved Lap-Band Trial for Teens being performed at Morgan Stanley Children's Hospital and Columbia University Medical Center, followed 14 adolescents -- six boys and eight girls -- between the ages of 14 and 17 who were, on average, 174 pounds overweight. Patients received dietary counseling and encouragement to exercise, both before and after surgery.

Exercise reduces hunger in lean women but not obese women

Tue, 17 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Exercise does not suppress appetite in obese women, as it does in lean women, according to a new study. The results were presented Tuesday, June 17, at The Endocrine Society's 90th Annual Meeting in San Francisco.

This [lack of appetite suppression] may promote greater food intake after exercise in obese women, said Katarina Borer, PhD, a University of Michigan researcher and lead author of the study. This information will help therapists and physicians understand the limitations of exercise in appetite control for weight loss in obese people.

Borer and her co-workers sought to better understand how changes in body fat level influence appetite and a hormone called leptin, which in animals curbs appetite when body fat increases. When leptin levels rise, it supposedly shuts off appetite and motivates physical activity to burn calories. However, as obese people become fatter, their leptin levels rise, but they become resistant to the actions of this hormone.

The hormone doesn't do the job it's supposed to do in lean people, Borer said.

In research funded by the National Institutes of Health, Borer's group studied 20 postmenopausal women: 10 lean and 10 obese women. The women ate three weight-maintenance meals a day while participating in three experiments on three separate days. During one experiment they did not exercise.

In the other two experiments the women exercised on a treadmill in the morning and the afternoon. They burned 500 calories each time, for a total of 1,000 calories a day. These two experiments differed by exercise intensity. One involved walking at high intensity, or 80 percent of maximal effort, for 7.5 minutes, with 10-minute rest periods between 10 walking sessions. The other experiment was half as intense (40 percent of peak effort) and involved walking for 15 minutes and resting for 5 minutes.

Every hour and before each meal, subjects recorded their appetite level on a 10-point scale ranging from not at all hungry to extremely hungry. Blood samples were collected every 15 to 60 minutes for hormone measurements.

Obese women claimed they were less hungry than lean women before meals and reported no appetite suppression during exercise, Borer said.

As expected, obese women had much higher leptin levels than in lean women, study data showed. But during intense exercise, obese women did not have reduced production of leptin, as lean women did. Only moderate-intensity exercise lowered leptin in obese women.

Obesity interferes with leptin's detection of exercise energy expenditure and with appetite suppression, Borer said. Obese women perhaps need to consciously watch their calories because some of the hormonal satiety [fullness] signals don't seem to work as well.

New weight loss diet recommends high-carb and protein big breakfast

Tue, 17 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers have found a possible way to overcome the common problem of dieters eventually abandoning their diet and regaining the weight they lost. Eat a big breakfast packed with carbohydrates (carbs) and protein, then follow a low-carb, low-calorie diet the rest of the day, the authors of a new study recommend. Results were presented Tuesday, June 17, at The Endocrine Society's 90th Annual Meeting in San Francisco.

Most weight loss studies have determined that a very low carbohydrate diet is not a good method to reduce weight, said lead author Daniela Jakubowicz, MD, of the Hospital de Clinicas, Caracas, Venzezuela. It exacerbates the craving for carbohydrates and slows metabolism. As a result, after a short period of weight loss, there is a quick return to obesity.

Only five percent of carbohydrate-restrictive diets are successful after two years, Jakubowicz said. Most carbohydrate-restrictive diets, she said, do not address addictive eating impulses.

With scientists from Virginia Commonwealth University in Richmond, Jakubowicz and her colleagues conducted a study, which they said shows that a diet's long-term effectiveness depends on its ability to increase a sense of fullness and bring down carb cravings. They compared their new diet with a strict low-carb diet in 94 obese, physically inactive women. Both diets were low in fat and total calories but differed in the carbohydrate distribution.

Forty-six women were on the very-low-carb diet, which allowed them to eat 1,085 calories a day. The diet consisted of 17 grams of carbohydrates, 51 grams of protein and 78 grams of fat a day. The smallest meal was breakfast, at 290 calories. For breakfast the dieters were permitted only 7 grams of carbohydrates, such as bread, fruit, cereal and milk. Dieters could eat just 12 grams of protein, such as meat and eggs, in the morning.

On the modified low-carb diet, or big-breakfast diet, the other 48 dieters ate 1,240 calories a day. Although lower in total fat (46 grams) than the other diet, the new diet had higher daily allotments of carbs (97 grams) and protein (93 grams). Dieters ate a 610-calorie big breakfast, consisting of 58 grams of carbs, 47 grams of protein and 22 fat grams. The diet schedule for lunch was 395 calories (34, 28 and 13 grams of carbs, protein and fat, respectively); dinner was 235 calories (5, 18 and 26 grams, respectively).

The first half of the eight-month study focused on weight loss, and the last four months on weight maintenance. At four months, the women on the strict low-carb diet dropped an average of about 28 pounds, and the women on the big-breakfast diet lost nearly 23 pounds on average, which according to Jakubowicz was not significantly different. But at 8 months, the low-carb dieters regained an average of 18 pounds, while the big-breakfast group continued to lose weight, shedding another 16.5 pounds. Those on the new diet lost more than 21 percent of their body weight, compared with just 4.5 percent for the low-carb group. Furthermore, the study found that women who ate a big breakfast reported feeling less hungry, especially before lunch, and having fewer cravings for carbs than the other women did.

Jakubowicz said the big-breakfast diet works because it controls appetite and cravings for sweets and starches. It also is healthier than an extremely low-carbohydrate diet, according to Jakubowicz, because it allows people to eat more fruit and therefore get enough fiber and vitamins. She said she has successfully used the diet in her patients for more than 15 years.

Hormone disorder may contribute to lack of menstruation in teenage athletes

Mon, 16 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers from Harvard University have found a way to predict which teenage female athletes will stop menstruating, an important risk factor for bone thinning, according to a preliminary study. The results will be presented at The Endocrine Society's 90th Annual Meeting in San Francisco.

Amenorrhea, or absence of menstruation, occurs in as many as 25 percent of female high school athletes, compared with 2 to 5 percent in the general population, according to the study's presenter, Madhusmita Misra, MD, a pediatric endocrinologist at Harvard-affiliated Massachusetts General Hospital, Boston.

Amenorrhea in athletes is known to cause infertility and early onset of low bone density and may increase the risk of breaking bones. Evidence suggests that intense exercise associated with caloric restriction, and therefore a state of energy deficit, is most responsible for menstrual irregularities among athletes.

The hormonal factors that link energy deficit and the stopping of periods in athletes are not well characterized, she said. These factors are important to determine in order to develop therapies that will lead to resumption of periods and hence improved bone density.

In females ages 12 to 18, Misra and her colleagues measured levels of various hormones, including ghrelin. Giving ghrelin to animals and humans has been shown to cause impaired secretion of hormones that regulate ovarian and menstrual function, and ghrelin levels are elevated in people with anorexia nervosa, another condition of severe energy deficit, she said. Until now, ghrelin levels have not been studied in teenage athletes in relation to ovarian hormones.

The researchers studied 21 teenage athletes with amenorrhea, 19 normally menstruating athletes and 18 nonathletic girls. The body mass index, a measure of body fat, was lower in the amenorrheic girls than in the other two groups, but overall these athletes were not underweight. All girls were more than 85 percent of the ideal body weight for their ages. The amenorrheic group reported similar levels of physical activity as the normally menstruating group, and both groups of athletes reported more physical activity than the non-athletic group.

Even after controlling for BMI, the research team found that ghrelin levels were higher in athletes that were not menstruating than in either of the other two groups. The data also showed that athletes with higher ghrelin levels had lower levels of the sex hormones estrogen and testosterone.

These findings suggest that hormonal disorders may explain why amenorrhea occurs in some but not all adolescent athletes, Misra said. In addition, ghrelin may be an important link between an energy deficit state and the hormones that regulate menstrual function.

They plan to further study the role of ghrelin in menstrual function in more subjects and over an extended time.

Adult stem cells improve fracture healing

Mon, 16 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Adult stem cells improve healing of broken bones and could eventually serve as a new treatment for the 10 to 20 percent of fractures that fail to heal, according to a new study. The results will be presented Monday, June 16, at The Endocrine Society's 90th Annual Meeting in San Francisco, by Froilan Granero-Molto, PhD, research associate of the University of North Carolina.

Lack of fracture repair often leads to several surgeries, long periods of immobilization, pain, bone deformities, and sometimes death, said the study's senior investigator, Anna Spagnoli, MD, of the University of North Carolina. The precise reason why a patient's fracture does not heal remains unknown in most cases.

Researchers believe a key reason for bone union failure may be a deficiency in adult stem cells, which normally become reparative cells in response to damage. Stem cells in human bone marrow, called mesenchymal stem cells, can become bone, cartilage, fat, muscle, and blood vessel cells, according to Spagnoli. Directing these stem cells into the repair mode is one of the objectives of a new branch of medicine called regenerative medicine.

These adult stem cells, which can be obtained from a patient's bone marrow in a minimally invasive procedure, have been reported to improve fracture healing in a few patients, Spagnoli said. However, animal studies are needed before clinical trials can begin.

Therefore, Spagnoli and her coworkers performed a study in mice with leg fractures. They took adult stem cells from the bone marrow of mice and engineered the cells to express a potent bone regenerator, insulin-like growth factor 1 (IGF-1). Then they transplanted the treated cells into mice with a fracture of the tibia, the long bone of the leg. Using computed tomography (CT or CAT) scanning, they showed that the treated mice had better fracture healing than did untreated controls. They found that the stem cells migrated to the fracture site and increased the bone and cartilage that bridged the bone gap.

Our study provided critical data needed to implement a novel therapeutic approach in patients with impaired fracture healing, Spagnoli said.

If scientists can duplicate the results of this animal study in humans, it may lead to a way to help the 600,000 people in the United States every year who suffer fractures that do not heal properly, she added.

Use of adult stem cells would have several advantages over embryonic stem cells. According to Spagnoli, they do not have the ethical controversy that surrounds embryonic stem cells, and they may avoid the immune rejection response, since the patient's own cells can be used.

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.

First study to examine vitamin D insufficiency in pediatric patients with low bone density

Mon, 02 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Vitamin D insufficiency is common in adults and is emerging in the world of pediatrics. A mild degree of vitamin D deficiency, also known as vitamin D insufficiency, causes rickets in children and can be treated with increased amount of nutritional vitamin D intake as well as increased sun exposure.

A new study conducted by physicians and researchers at Nationwide Children's Hospital, is the first study to investigate vitamin D insufficiency in pediatric patients with low bone density.

According to the study, published in the June issue of Pediatrics, among the 85 patients studied, 80 percent had a vitamin D insufficiency. All the patients had a history of bone fragility or underlying chronic medical conditions that put them at a risk of osteoporosis, which is not just an adult disease, but is seen in children and can originate during childhood. Vitamin D insufficiency may contribute to low bone mass or even make the underlying metabolic bone disease worsen if not treated. Vitamin D is essential in bone growth and mineralization in children and adults.

The study's lead author, Sasigarn Bowden, MD, a pediatric endocrinologist and attending physician in the Metabolic Bone Clinic at Nationwide Children's explains, We need to check vitamin D levels in all patients with history of multiple fractures or low bone density and treat the vitamin D problem if the levels are low. The supplementation of vitamin D should be a priority in the management of pediatric patients with osteoporosis or osteopenia in order to optimize their bone health and potentially prevent fractures.

Potential factors that may account for vitamin D insufficiency in various chronic medical conditions include low vitamin D intake and decreased sun exposure. Four studies in Europe found that 80 percent of healthy children and adolescents had insufficient vitamin D levels in the winter.

Due to the number of recent studies of healthy children or adolescents with a high prevalence of vitamin D insufficiency, the public should be aware of the fact that it is common, especially living in high altitude, said Bowden, also an assistant professor of Pediatrics at The Ohio State University College of Medicine. Sometimes our vitamin D levels get low at the end of winter due to less exposure to sunlight, but if we take a multivitamin D supplement, or consume an adequate amount of vitamin D from dietary sources such as vitamin D fortified milk or orange juice, we should be okay throughout the entire year.

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.

Rare syndrome provides clues on obesity, blood pressure

Mon, 03 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) University of Iowa researchers have found a clue about how resistance to the hormone leptin might disrupt the brain signals that tell the body when to stop eating. The research, which focused on the rare genetic disorder Bardet-Biedl syndrome (BBS), also found an association between leptin resistance and high blood pressure.

The findings, which were based on mouse models developed at the UI, have implications for treating BBS as well as obesity and high blood pressure in people without BBS. The study appeared online March 3 in the Journal of Clinical Investigation.

Bardet-Biedl syndrome is rare but its symptoms, including obesity and increased risk of heart disease, are similar to problems faced by many people without the syndrome, said Kamal Rahmouni, Ph.D., the study's principal investigator and assistant professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine. Leptin normally suppresses appetite and increases caloric use. The more we know about how leptin and gene defects affect people with BBS, the more likely it is that we can improve treatment for them and people with similar symptoms.

The research builds on previous BBS findings, including research led by current study team member Val Sheffield, M.D., Ph.D., the Martin and Ruth Carver Chair in Genetics and professor of pediatrics at the UI and a Howard Hughes Medical Institute investigator.

Fewer than one in 10,000 people have BBS. Sheffield, who has discovered or co-discovered the majority of the 12 known BBS genes, developed BBS mice that have the same features as the human condition. The study used a mouse model without BBS and three mouse models that each lacks a protein (Bbs2, Bbs4 or Bbs6) due to a BBS gene deletion.

The team measured daily food intake and body weight of each mouse. Some mice also received daily leptin injections. Mice without BBS lost weight when injected with leptin. However, the mice with any of the three types of BBS gene defects did not respond to leptin and gained weight.

Rahmouni, who has expertise in metabolism and obesity, said the hormone leptin is an obvious candidate when looking at causes of weight gain.

Leptin is made in adipose (fat) tissue and is supposed to decrease fat stores. However, if we find high levels of it in the plasma, and people still are obese, we know it's not acting correctly and that there is leptin resistance, he said.

The team also found that even very young mice with BBS, whose body weights were the same as the non-BBS mice, had high levels of leptin in the plasma, indicating leptin resistance. The team then looked at a specific brain region of mice with BBS to understand why this occurred.

We know that leptin regulates body weight and food intake through the hypothalamus in the brain. In the mice with BBS, we saw that Pomc, one of the three main genes normally regulated by leptin, was not properly regulated, Rahmouni said.

This finding allowed us to pinpoint a very specific defect that explains why these mice are obese. The brain normally uses the Pomc gene to tell the body to stop eating, but in the animals with BBS, it doesn't work and so the mice won't feel full. We know that people without this gene have the same symptoms as the mice in our study, so the finding is meaningful, he added.

Rahmouni and colleagues will next examine the specific deficit in the neurons in the brain that might cause the problem with the Pomc (pronounced pom-c) gene.

In another aspect of the study, the team saw that two of the three mouse models with BBS protein problems (Bbs4 and Bbs6) had high blood pressure. Recent research published by another institution has pointed to the same problem in humans with the same gene defects.

The UI team found that using a chemical to block neurotransmission in mice with the Bbs4 and Bbs6 gene defects lowered blood pressure.

Because there are so few people with BBS, mouse models are very helpful in trying to understand the blood pressure problem, Rahmouni said. Currently, there is no specific recommendation on what drug or level of drug to use to treat hypertension in BBS patients. In addition, this work may lead to improved treatment of hypertensive patients without BBS. We hope to learn more about the mechanism in order to improve and even customize treatment.

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.

Overweight people may not know when they've had enough

Wed, 09 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) UPTON, NY - Researchers at the U.S. Department of Energy's Brookhaven National Laboratory have found new clues to why some people overeat and gain weight while others don't. Examining how the human brain responds to satiety messages delivered when the stomach is in various stages of fullness, the scientists have identified brain circuits that motivate the desire to overeat. Treatments that target these circuits may prove useful in controlling chronic overeating, according to the authors. The study is published online and will appear in the February 15, 2008 issue of NeuroImage.

By simulating feelings of fullness with an expandable balloon we saw the activation of different areas of the brain in normal weight and overweight people, said lead author Gene-Jack Wang of Brookhaven Lab's Center for Translational Neuroimaging. The overweight subjects had less activation in parts of the brain that signal satiety in normal weight subjects. The overweight subjects were also less likely than normal weight subjects to report satiety when their stomachs were moderately full. These findings provide new evidence for why some people will continue to eat despite having eaten a moderate-size meal, said Wang.

Wang and colleagues studied the brain metabolism of 18 individuals with body mass indices (BMI) ranging from 20 (low/normal weight) to 29 (extremely overweight/borderline obese). Each study participant swallowed a balloon, which was then filled with water, emptied, and refilled again at volumes that varied between 50 and 70 percent. During this process, the researchers used functional magnetic resonance imaging (fMRI) to scan the subjects' brains. Subjects were also asked throughout the study to describe their feelings of fullness. The higher their BMI, the lower their likelihood of saying they felt full when the balloon was inflated 70 percent.

One notable region of the brain - the left posterior amygdala - was activated less in the high-BMI subjects, while it was activated more in their thinner counterparts. This activation was turned on when study subjects reported feeling full. Subjects who had the highest scores on self-reports of hunger had the least activation in the left posterior amygdala.

This study provides the first evidence of the connection of the left amygdala and feelings of hunger during stomach fullness, demonstrating that activation of this brain region suppresses hunger, said Wang. Our findings indicate a potential direction for treatment strategies - be they behavioral, medical or surgical -- targeting this brain region.

The scientists also looked at a range of hormones that regulate the digestive system, to see whether they played a role in responding to feelings of fullness. Ghrelin, a hormone known to stimulate the appetite and cause short-term satiety, showed the most relevance. Researchers found that individuals who had greater increases in ghrelin levels after their stomachs were moderately full also had greater activation of the left amygdala. This indicates that ghrelin may control the reaction of the amygdala to satiety signals sent by the stomach, said Wang.

This study was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science, the National Institute on Drug Abuse (NIDA), the National Institute of Diabetes and Digestive and Kidney Diseases, the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the General Clinical Research Center at University Hospital Stony Brook. DOE has a long-standing interest in research on brain chemistry gained through brain-imaging studies. Brain-imaging techniques such as MRI are a direct outgrowth of DOE's support of basic physics and chemistry research.

The current study is part of a major focus of research at Brookhaven Lab on the neurobiology of eating disorders and obesity and their treatment. Earlier studies at the Lab have:

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.

Melatonin could hurt memory formation at night

Thu, 15 Nov 2007 13:51:18 PST

( from http://www.rxpgnews.com ) What do you do when a naturally occurring hormone in your body turns against you? What do you do when that same hormone – melatonin – is a popular supplement you take to help you sleep? A University of Houston professor and his team of researchers may have some answers.

Gregg W. Roman, assistant professor in the department of biology and biochemistry at UH, describes his team’s findings in a paper titled “Melatonin Suppresses Nighttime Memory Formation in Zebrafish,” appearing Nov. 16 in Science, the world’s leading journal of original scientific research, global news and commentary.

Frequently called “the hormone of darkness,” melatonin is a hormone the body produces that may regulate patterns of sleeping and awakening in humans. In almost all organisms tested, this antioxidant’s natural levels are high during the night and low during the day. In addition to what the body produces naturally, many people also take melatonin supplements to fight jet lag, balance out seasonal affect disorder and regulate nighttime dementia.

Roman says, however, that melatonin could actually be hurting you at night, finding in a study with zebrafish (Danio rerio) that melatonin directly inhibits memory formation.

“This work is about the mechanism by which the biological clock controls the formation of new memories,” Roman said. “We were interested in the circadian control – the day-night cycle control – of learning and memory formation. We found zebrafish are capable of learning very well during their active phase during the day, but learn very poorly at night during their sleep or quiet phase.”

The experiments were performed using zebrafish for several reasons. They’re small and breed in large numbers (thereby being less expensive to use), and they are diurnal, having the same activity rhythms as people. Zebrafish are most active during the day and less active at night, whereas many other vertebrate model systems, such as rodents, are nocturnal. Roman reasons that if you are interested in how the biological clock regulates cognitive function in humans, you should use a model system that reacts to the clock the same way people do.

More than two years worth of work, including the discovery that the ability to learn and remember was controlled by an endogenous (or internal) clock originating within the zebrafish, led Roman and his colleagues to hypothesize that melatonin may be responsible for poor learning and memory formation during the night. In order to test whether melatonin was involved in inhibiting nighttime learning and memory formation, they treated the zebrafish during the day with this hormone to see how the fish performed. Interestingly, melatonin failed to affect learning, but dramatically inhibited the formation of new memories, with the melatonin-treated fish resembling fish trained during the night in a test for 24-hour memory.

“The next step was to inhibit melatonin signaling during the night with a melatonin receptor antagonist and test for effects on memory formation,” Roman said. “It was tremendous – the results were, excuse the expression, like night and day. We saw dramatic improvements in nighttime memory formation by inhibiting melatonin signaling, indicating that the reason the zebrafish did not form memories at night was because of the melatonin hormone.”

Next, with the pineal gland being the primary source of melatonin in fish and in people, Roman’s student Oliver Rawashdeh removed this gland from the fish and found they could now form memories at high levels even during the night. Removing this melatonin-producing gland allowed the researchers to alleviate the hormone’s negative side effects, further demonstrating that melatonin inhibits the formation of new memories during the night.

With these findings, Roman hopes to be able to retain the beneficial effects of melatonin’s antioxidant properties. Such benefits include fighting free radical damage to slow some forms of neurodegeneration, such as in Parkinson’s and Alzheimer’s diseases, and stopping DNA damage, which has potential to act as a preventative against cancer. And, since the positive antioxidant effect is direct and independent of receptor signaling, there is hope that removing the melatonin receptor signaling will combat only this hormone’s negative effects on cognitive function.

Additionally, Roman said that inhibiting melatonin signaling with receptor antagonists may help with a large number of nighttime cognitive tasks, helping such people as students studying for finals, airplane pilots, ER physicians and night-shift workers. Roman also thinks that a natural role of melatonin may be to facilitate the storage of memories made during the day and that more studies are required to understand the ultimate role melatonin has in memory formation.

“The value of melatonin as a supplement is largely due to its antioxidant properties,” Roman said. “The use of melatonin receptor antagonists will not affect this attribute, but may alleviate an important side effect on nighttime cognitive function.”

In other words, a ‘best of both worlds’ scenario could result, taking advantage of melatonin’s antioxidant benefits while improving nighttime memory formation that is now inhibited by it.

Roman’s team at UH for this breakthrough study includes Gregory M. Cahill, associate professor of biology and biochemistry, and two of their students and research assistants, Oliver Rawashdeh and Nancy Hernandez de Borsetti.

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.

Sex hormone signature indicates gender rather than just chromosomes

Wed, 17 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Help with assigning gender could one day be at hand for intersex individuals whose genital phenotypes and sex chromosomes don't match, thanks to the discovery of a stable sex hormone signature in our cells.

In an article published today in the online open access journal BMC Genomics, researchers have shown for the first time that testosterone leaves an irreversible molecular signature in cells that may provide a far more sophisticated way to look at sex than just ascertaining the presence of the Y chromosome. A team of researchers from the US and Germany were able to pinpoint the role of testosterone by comparing individuals with complete androgen insensitivity syndrome (CAIS) to people without CAIS. The findings provide a platform for future work that may lead to improved counselling for those whose gender is ambiguous.

Lead researcher, Professor Paul-Martin Holterhus, of University-Hospital Schleswig-Holstein, Kiel, Germany, said: Androgens have long lasting effects during certain sensitive stages of our genital development and this is probably true for other organs. He adds It is currently increasingly accepted that the brain shows sex-specific development in response to presence or absence of testosterone. This affects sex specific behaviour and probably modulates gender identity.

The role of androgens - especially the male-defining hormone testosterone - in sexual development has long been known. Gender programming begins in the embryo and is thought to continue throughout life, particularly during puberty. However, what's not currently known is the different roles of sex chromosome genes versus the long-term programming effects of sex hormones, namely androgens.

Individuals with CAIS, which affects 1 in 20,000 people, look like normal females. But at a genetic level CAIS women have XY sex chromosomes rather than the usual XX. The condition is due to mutations in the gene coding for the androgen receptor, which means that androgen signalling doesn't work: it essentially knocks out the effect of testosterone. The researchers used skin biopsies of external genitalia to compare the gene expression of normal males and CAIS females. Analysis revealed that between males and females, 440 genes differed in their level of transcription. The activity levels of these genes form a 'signature' that they used to evaluate partial androgen insensitivity syndrome (AIS) samples and could be developed to help understand more about individual AIS cases.

Since we compared XY females with the XY males, the difference can only be explained by differences in androgen action and not by differences in sex chromosomes, explains Professor Holterhus. Another intriguing observation is that the one normal female (with a 46,XX genotype) in our study did not differ a lot with respect to the identified genes from the XY females. This is an important reassurance for XY females because it limits the role of the sex chromosomes in gender assignment.

Insulin's brain impact links drugs and diabetes

Tue, 16 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Insulin, long known as an important regulator of blood glucose levels, now has a newly appreciated role in the brain.

Vanderbilt University Medical Center researchers, working with colleagues in Texas, have found that insulin levels affect the brain�s dopamine systems, which are involved in drug addiction and many neuropsychiatric conditions.

In addition to suggesting potential new targets for treating drug abuse, the findings raise questions as to whether improper control of insulin levels � as in diabetes � may impact risk for attention deficit hyperactivity disorder (ADHD) or influence the effectiveness of current ADHD medications.

The study, led by Aurelio Galli, Ph.D., in the Center for Molecular Neuroscience and Calum Avison, Ph.D., in the Institute of Imaging Science (VUIIS), appears online this week in the Public Library of Science Biology (PLoS Biology).

The psychostimulant drugs amphetamine and cocaine, as well as related medications for ADHD, block the reuptake of the neurotransmitter dopamine by dopamine transporters (DATs) and increase the level of dopamine signaling. Some of these compounds, including amphetamine, also cause a massive outpouring of dopamine through DATs.

The resulting surge of synaptic dopamine alters attention, increases motor activity and plays an important role in the addictive properties of psychostimulants.

But the link between insulin status and dopaminergic function is not readily apparent.

�In the 1970s, there were articles showing that, in animals with type 1 diabetes, psychostimulants like amphetamine would not increase locomotor behavior,� said Galli, associate professor of Molecular Physiology and Biophysics. �We didn�t have a clear understanding of why that was happening.�

This sparked Galli and colleagues to investigate the link between insulin signaling and amphetamine action.

Using a rat model of type 1 � or juvenile � diabetes in which insulin levels are depleted, Galli�s group assessed the function of the dopaminergic pathway in the striatum, an area of the brain rich in dopamine.

In the absence of insulin, amphetamine-induced dopamine signaling was disrupted, they found. Dopamine release in the striatum was severely impaired and expression of DAT on the surface of the nerve terminal � where it normally acts to inactivate dopamine � was significantly reduced.

The lack of the protein on the plasma membrane prevents the amphetamine-induced increase in extracellular dopamine, and in turn, amphetamine fails to activate the dopamine pathways that stimulate reward, attention and movement, Galli noted.

The researchers then restored insulin by pulsing the hormone back into the brain of the diabetic animals and found that the system returns to normal, indicating that the lack of insulin in the striatum directly affected amphetamine action.

To connect the physiological findings to activity in the intact brain, collaborators in the VUIIS, led by Avison, developed a probe for brain DAT activity using functional magnetic resonance imaging (fMRI).

�You can do molecular dissection in very well defined model systems and break the system down into its constituents,� said Avison, professor of Radiology and Radiological Sciences, and professor of Pharmacology. �But the question is: how does that relate to the intact brain? What�s the relevance to overall functioning in the intact system?�

Working with Galli and Avison, Jason Williams, Ph.D., used fMRI to demonstrate that in normal, healthy rats with plenty of insulin, amphetamine increased neural activity in the striatum. But in diabetic animals, activity in the striatum was suppressed.

�This finding is in vivo evidence that, in the intact diabetic rat, loss of insulin has compromised DAT trafficking to the plasma membrane,� Avison said. �These experiments show that there is likely a strong interplay between these important dopamine neurotransmitter systems and insulin signaling mechanisms, which we know are altered in diabetes�

The results are some of the first to link insulin status and dopaminergic brain function and hold several implications for human health and disease.

�This is really the first mechanistic connection in vivo between diabetes and amphetamine action,� Galli said. �This offers a completely new perspective on the influence of this disease (diabetes) on brain function, as well as diseases with altered dopamine signaling, such as schizophrenia and ADHD.�

The findings suggest that ADHD risk may have an insulin-dependent component and that control of insulin levels and response to the hormone may be an important determinant of amphetamine efficacy in patients with ADHD, Galli noted.

�We have described a novel mechanism by which diabetes may affect brain function.�

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.�

Depression, aging, and proteins made by a virus may all play role in heart disease

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio � Researchers here have linked an increase in two immune system proteins essential for inflammation to a latent viral infection and proposed a chain of events that might accelerate cardiovascular disease.

The same process may be involved in a host of other ailments plaguing the elderly.

The findings also suggest that chronic depression may play a key role in starting the cascade that can lead to the buildup of plaques clogging coronary arteries.

The researchers' report, their latest in a nearly three-decade-long effort to understand the role psychological stress plays in weakening the immune system, was published in the journal Brain, Behavior and Immunity.

Ronald Glaser, a professor of molecular virology, immunology and medical genetics at Ohio State University , said, �To me, this suggests a new way of thinking about how these diseases develop. We carry around these latent herpes viruses in our bodies virtually all our lives and periodically they can hurt us, inducing biological events that could lead to an increased risk of atherosclerosis.�

Glaser, head of Ohio State's Institute for Behavioral Medicine Research, has focused for years on Epstein-Barr virus (EBV), one of eight different herpesviruses that can remain dormant in the body for a lifetime.

�Perhaps more than 90 percent of the people in North America have been infected by EBV by the time they're adults,� Glaser said. �Virtually everybody in the country is carrying this virus.�

Glaser, James Waldman, an associate professor of pathology, Marshall Williams, a professor of molecular virology, immunology and medical genetics, and Janice Kiecolt-Glaser, a professor of psychiatry and psychology, initially focused on the role that two essential proteins � interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) -- play in producing inflammation, a major part of the body's immune response.

As the immune system ages, the levels of IL-6 in the body increase in the blood. Some of that IL-6 is created by immune cells called macrophages that rush to the site of an infection or injury. Earlier work by the team also showed that increases in psychological stress and depression can substantially raise the levels of IL-6 and TNF-a in the body.

Increased stress and depression can also trigger the latent virus to reactivate and begin reproducing inside cells

The researchers also knew that as Epstein-Barr virus begins to multiply in cells in the body, it produces a protein called dUTpase that, in turn, can stimulate macrophages to make even more IL-6.

�The more IL-6 levels rise in the body, the greater a person's risk is for disease,� Glaser said, adding that IL-6 increases, as well as depression, have been associated with cardiovascular disease, osteoporosis and type-2 diabetes.

The researchers developed a model to test these linkages by using endothelial cells that line the inside of veins in umbilical cord tissue. They wanted to see how the cells themselves, as well as the immune macrophages, reacted when exposed to the virus as well as the dUTpase protein.

In those experiments, the production of IL-6, as well as TNF-a, were increased just as they would be as part of the inflammatory process in the body. Such chronic incidents of inflammation are integral to the onset of atherosclerosis, Waldman said, as well as other diseases.

�Basically, we're seeing all of these factors as playing a significant role in the production of these proinflammatory proteins,� he said. �We were very surprised to find all these connections. They weren't expected.

�This may help us understand just how atherosclerotic disease may occur, or how it is exacerbated by many factors.�

The researchers point to one value of their findings:

�People need to remember how important depression is, and that when they're depressed, it can reactivate these viruses, starting the cascade that leads to inflammation, perhaps increasing the risk of cardiovascular disease, according to Glaser.

�So treating depression is very important,� he said.

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.�

Brain system serves as 'remote control' for fat metabolism

Thu, 20 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CINCINNATI�A system in the brain already known to regulate food intake also serves as a direct �remote control� for the way fat is stored and metabolized in the body, say University of Cincinnati (UC) researchers.

What is known as the melanocortin system, the researchers say, controls fat metabolism and the way it accumulates in the body completely independently of food intake.

The finding, the researchers report, could lead to the development of new and urgently needed medications to treat the growing, worldwide obesity epidemic.

Led by Matthias Tsch�p, MD, UC associate professor of psychiatry, and coauthored by scientists at the German Institute of Human Nutrition, the study appears in the Sept. 20, 2007, online edition of the Journal of Clinical Investigation.

The melanocortin system was previously identified as a �control loop� in the central nervous system (CNS) that receives hormonal signals from the gut�like those given off by �hunger� and �satiety� hormones such as ghrelin and leptin�and responds to these sensations of hunger or fullness by causing the body to either ingest or burn calories.

Tsch�p and colleagues say that beyond responding to signals of hunger or satiety, the melanocortin system also controls whether extra energy (glucose) will be converted to fat and whether it will be stored or metabolized.

�Understanding how specific CNS circuits directly control fat storage and metabolism is essential in order to achieve a breakthrough in this important area of research,� the authors write.

The group studied the melanocortin system at the molecular level in rodents. They found that when the system is stimulated to increase activity, fat is metabolized. When activity in the system is reduced�either pharmacologically or genetically�fat accumulation increases.

�We were able, in essence, to change traffic signals in so-called nutrient highways in the body so that calories were metabolized, and not dumped into fat cells,� says Tsch�p. �And we did this without changing the rate of food intake.

�These findings are relevant for human obesity, since mutations in the system we studied here are the most common known reason for genetically caused obesity in humans,� Tsch�p added.

The study authors also reported clinical data from coauthors I. Sadaf Farooqi and Stephen O�Rahilly. Their studies in humans with activity-reducing genetic variations in the melanocortin system indicate that fat metabolism may be �remote controlled� by the human brain similar to the way it is in rodents.

The Centers for Disease Control (CDC) and Prevention estimates that more than 30 percent of adults aged 20 to 74 are obese. Obesity increases chances for developing diabetes, heart disease and some cancers.

Cedars-Sinai hormone expert outlines causes and treatments for breast growth in men in NEJM

Wed, 19 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) LOS ANGELES (September 14, 2007) Gynecomastia, the benign enlargement of male breast tissue, is a common occurrence in adolescents as well as in middle-aged and older men. While there are several reasons why men develop breast tissue, it is usually not a health concern, often resolves on its own, and is generally treatable, according to a clinical practice article appearing in the September 20 issue of the New England Journal of Medicine (NEJM).

The clinical practice article, a regular NEJM feature that focuses on a case history highlighting a common clinical problem, was authored by Glenn D. Braunstein, M.D., chair of the Department of Medicine at Cedars-Sinai Medical Center and an expert in gynecomastia and other hormone-related diseases.

�Nearly half of all men will experience breast tissue growth during their lifetimes, but many are unaware of it or are too embarrassed to even discuss the problem with their doctor,� said Braunstein. �Raising awareness of the condition � its causes, symptoms, treatments � may help more boys and men with gynecomastia be correctly diagnosed, and reassure them that they are not alone in experiencing this.�

Gynecomastia is characterized by the presence of a rubbery or firm mass extending concentrically from the nipples. About half the time, it is detected in both breasts. Other, different conditions present with similar symptoms: pseudogynecomastia, which is fat deposition without glandular proliferation, and is increasing along with the incidence of obesity in American men; and carcinoma of the breast, which is much less common. Breast cancer in men is usually not symmetrical to the nipple, is generally found only on one side, and may be associated with skin dimpling or nipple discharge. Several other conditions may also lead to breast enlargement in men, including neurofibromas, hematomas, and dermatoid cysts, but they are rare.

Gynecomastia can be physiologic (occurring normally during infancy, puberty and older age), or pathologic (due to drugs or disorders such as androgen deficiency, testicular tumors, hyperthyroidism, and chronic kidney disease). In adult men, 50 percent of cases are due to persistent pubertal gynecomastia or medication side effects, and an additional 25 percent have no known cause.

The condition is most common during the normal hormone fluctuations of adolescence � nearly 65 percent of boys age 13 and 14 experience breast enlargement to some degree � but it usually resolves without intervention in late puberty. In adults and older men, gynecomastia can be the result of low testosterone or other hormone imbalances, medications, other illnesses, or an increase in body fat, which converts male hormones to estrogens. It also can be a side effect of hormone therapies prescribed to treat prostate cancer. Medications such as the antiestrogen drug tamoxifen, may alleviate the pain and tenderness that can accompany gynecomastia.

�I�ve seen hundreds of cases of gynecomastia � and in many of those, the men were not even aware that they had it. It�s fairly common, and in general, nothing to worry about from a medical standpoint,� said Braunstein, who is also holder of the James R. Klinenberg Chair in Medicine at Cedars-Sinai. �If, however, the growth of breast tissue is very recent in onset, or if it is accompanied by pain or tenderness, it should be brought to the attention of your doctor who should take a careful medical history followed by exam and blood tests to rule out hormonal disorders or malignancies.�

If no serious disease is found, and the gynecomastia persists for longer than one year or is troublesome to the man who is experiencing it, surgical removal of the breast tissue is an option that usually leads to a good cosmetic result. For patients with asymptomatic gynecomastia who are not particularly bothered by it, no treatment is necessary.

�This information should be reassuring to all men, but especially to adolescent boys and their parents who may be spending time worrying about this,� said Braunstein.

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.