RxPG News : Diabetes

Strong association between the consumption of red meat and risk of type 2 diabetes

Wed, 10 Aug 2011 18:27:02 PST

( from http://www.rxpgnews.com ) A new study by Harvard School of Public Health (HSPH) researchers finds a strong association between the consumption of red meat—particularly when the meat is processed—and an increased risk of type 2 diabetes. The study also shows that replacing red meat with healthier proteins, such as low-fat dairy, nuts, or whole grains, can significantly lower the risk.

The study, led by An Pan, research fellow in the HSPH Department of Nutrition, will be published online in the American Journal of Clinical Nutrition on August 10, 2011 and will appear in the October print edition.

Pan, senior author Frank Hu, professor of nutrition and epidemiology at HSPH, and colleagues analyzed questionnaire responses from 37,083 men followed for 20 years in the Health Professionals Follow-Up Study; 79,570 women followed for 28 years in the Nurses' Health Study I; and 87,504 women followed for 14 years in the Nurses' Health Study II. They also conducted an updated meta-analysis, combining data from their new study with data from existing studies that included a total of 442,101 participants, 28,228 of whom developed type 2 diabetes during the study. After adjusting for age, body mass index (BMI), and other lifestyle and dietary risk factors, the researchers found that a daily 100-gram serving of unprocessed red meat (about the size of a deck of cards) was associated with a 19% increased risk of type 2 diabetes. They also found that one daily serving of half that quantity of processed meat—50 grams (for example, one hot dog or sausage or two slices of bacon)—was associated with a 51% increased risk.

"Clearly, the results from this study have huge public health implications given the rising type 2 diabetes epidemic and increasing consumption of red meats worldwide," said Hu. "The good news is that such troubling risk factors can be offset by swapping red meat for a healthier protein."

The researchers found that, for an individual who eats one daily serving of red meat, substituting one serving of nuts per day was associated with a 21% lower risk of type 2 diabetes; substituting low-fat dairy, a 17% lower risk; and substituting whole grains, a 23% lower risk.

Based on these results, the researchers advise that consumption of processed red meat—like hot dogs, bacon, sausage, and deli meats, which generally have high levels of sodium and nitrites—should be minimized and unprocessed red meat should be reduced. If possible, they add, red meat should be replaced with healthier choices, such as nuts, whole grains, low-fat dairy products, fish, or beans.

Worldwide, diabetes has reached epidemic levels, affecting nearly 350 million adults. In the U.S. alone, more than 11% of adults over age 20—25.6 million people—have the disease, according to the Centers for Disease Control and Prevention. Most have type 2 diabetes, which is primarily linked to obesity, physical inactivity, and an unhealthy diet.

Previous studies have indicated that eating processed red meats increases the risk of developing type 2 diabetes. Risks from unprocessed meats have been less clear. For instance, in 2010, HSPH researchers found no clear evidence of an association between eating unprocessed meats and increased risk for either coronary heart disease or type 2 diabetes, but that study was based on smaller samples than the current study, and the researchers recommended further study of unprocessed meats. Another HSPH study in 2010 linked eating red meat with an increased risk of heart disease—which is strongly linked to diabetes—but did not distinguish between processed and unprocessed red meats.

This new study—the largest of its kind in terms of sample size and follow-up years—finds that both unprocessed and processed meats pose a type 2 diabetes risk, thus helping to clarify the issue. In addition, this study is among the first to estimate the risk reduction associated with substituting healthier protein choices for red meat.

"Our study clearly shows that eating both unprocessed and processed red meat—particularly processed—is associated with an increased risk of type 2 diabetes," said Pan. He noted that the 2010 U.S. dietary guidelines continue to lump red meat together with fish, poultry, eggs, nuts, seeds, beans, and soy products in the "protein foods" group. But since red meat appears to have significant negative health effects—increased risk of diabetes, cardiovascular disease, and even total mortality, as suggested by several recent studies—Pan suggested the guidelines should distinguish red meat from healthier protein sources and promote the latter instead.

Type 2 diabetes: 'Intensive' versus 'conventional' blood glucose control -- no clear picture

Mon, 01 Aug 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Research published in The Cochrane Library found that the risk of death and cardiovascular disease, such as stroke, was unchanged whether glucose control was intense or conventional. They did find, however, that when aiming to keep blood glucose levels at the lower intensive level, the chance of damaging small blood vessels in the body, potentially leading to damage in the eyes and kidneys, is reduced. But aiming for this lower level with the more intensive glucose control substantially increased the risk that a person's blood glucose could drop too low, potentially resulting in loss of consciousness or even death if untreated.

Bianca Hemmingsen and colleagues from the Copenhagen Trial Unit in Denmark reached these conclusions after studying all published clinical trials comparing intensive glycaemic control with conventional glycaemic control. They identified 20 trials on patients with type 2 diabetes that together involved a total of 29,986 participants.

Keeping blood glucose levels under control is the goal of all treatments for people with type 2 diabetes. There is an active debate between experts about the level of blood glucose that patients should aim for. Some argue that they should aim to keep blood glucose about or slightly above normal, and thereby avoid the risks of too low blood glucose, what doctors call hypoglycaemia. Others think patients should use a more intensive control that keeps blood glucose at the lower levels seen in non-diabetic people so that they avoid the risks associated with having too much blood glucose - hyperglycaemia.

The researchers did not find enough information to properly compare quality of life between people who aimed for the two different targets. However, Hemmingsen and colleagues hypothesized that intensive glycaemic control may negatively affect a person's quality of life when compared with aiming for conventional levels. Targeting the intensive levels means that many patients have to cope with complex and time consuming treatment. On top of this, they have the fear that their blood glucose might drop too low, says Hemmingsen.

In most people, cells in their pancreas monitor blood glucose and release precise amounts of the glucose-regulating hormone insulin so that the glucose level is maintained. In people with type 2 diabetes, this insulin regulating system fails. These people have to manage their own glucose levels through a mixture of exercise, weight control, diet and the use of a range of different medications.

With the numbers of people in the world with type 2 diabetes increasing, it is important that we work out the best way of helping them to manage their blood glucose levels, says Hemmingsen. She believes that there is still a clear need for large clinical trials investigating patient-relevant outcomes that randomly assign patients to clearly defined different glycaemic targets.

$3 million grant to aid minorities with uncontrolled diabetes

Thu, 28 Jul 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers at the University of Illinois at Chicago's Institute for Health Research and Policy and College of Medicine have received a $3 million federal grant to improve diabetes management in minority patients.

The grant will fund a five-year study to evaluate a new intervention designed to improve lifestyle behaviors and medication compliance and to intensify therapy in minority patients with uncontrolled type 2 diabetes.

African-Americans and Latinos with diabetes often do not reach desired blood sugar, blood pressure or cholesterol levels, placing them at high risk for complications or death.

We know there's a breakdown in the current health care system, said Lisa Sharp, assistant professor of medicine and co-principal investigator of the study. Even when patients have access to quality health care, there are many other economic, social and cultural factors that contribute to them not meeting their therapeutic goals.

The researchers will enroll 300 African-American and Latino adults with uncontrolled diabetes from the University of Illinois Medical Center. Patients will be randomly assigned to one of two groups.

In the first group, a clinic-based pharmacist will educate patients about diabetes, reconcile their medications, and address any compliance barriers.

In the second group, a community-based lay health worker (or health promoter) will team with the clinic-based pharmacist to assist with cultural and language barriers, reinforce educational messages, provide support, help solve problems related to compliance, and assist in continuity of care.

The pharmacist, working with a lay health worker, may help create a bridge, because there's this huge chasm between the patient and the health care provider, said Dr. Ben Gerber, associate professor of medicine. A lot of times, people will leave their doctor's office, and they have a lot of questions and don't understand things.

For example, a physician may prescribe a new insulin pen, but the patient may not know how to use it properly. The pharmacist may demonstrate it, but some patients may need additional practice that can be reinforced by a health promoter. Language barriers may also hinder understanding.

After one year, the participants who didn't receive health promoters will begin to receive health promoter support, while health promoter support for the other group will be phased out to assess maintenance and clinical outcomes.

There needs to be some adaptability to serve the patient's needs, said Gerber, co-principal investigator of the study.

Patients often bounce from the emergency room to the clinic to home and back again. Often there is a hands-off approach to figuring out what may be causing missed appointments or medication lapses, Gerber said.

Instead, we should try to figure out what the problems might be because if we address them it might actually help their ability to come to the clinic, to take their medicine, and maybe prevent them from being hospitalized, especially for diabetes-related problems, Gerber said.

Teens with type 2 diabetes already show possible signs of impaired heart function

Tue, 07 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Heart function may be affected in people with Type 2 diabetes as early as adolescence, according to a new study that will be presented Sunday at The Endocrine Society's 93rd Annual Meeting in Boston.

Past studies in adults with Type 2 diabetes show that their heart and blood vessels' ability to adapt to exercise may be impaired. Our study shows that these changes in heart function may begin to happen very early after Type 2 diabetes occurs, said the study's lead author, Teresa Pinto, MD, a pediatric endocrinologist at the Dalhousie University IWK Health Centre in Halifax, Nova Scotia, Canada.

Pinto performed the research while at the University of Auckland in New Zealand. The researchers studied how the heart and blood vessels of 13 teenagers with Type 2 diabetes adapted to exercise, compared with 27 overweight or obese subjects who did not have diabetes and 19 nondiabetic and nonobese control subjects. The subjects were ages 12 to 20 and from New Zealand. Their body composition, including percentage of body fat, was determined using dual-energy x-ray absorptiometry (DEXA) scans.

All subjects performed an exercise test on a stationary bicycle designed for use in a magnetic resonance imaging (MRI) machine. With MRI, images were taken of each subject's heart and femoral artery, a large blood vessel in the leg that supplies the leg with blood. MRI took place while the subjects were at rest and during or immediately after exercise on the cycle.

The images of the heart showed that the hearts of subjects with Type 2 diabetes did not expand and fill up with blood between heart beats as well as the hearts of subjects in the other two groups. This occurred during exercise only, the authors found. With exercise, the amount of blood pumped out with each heart beat (the cardiac output) was normal in all three groups, although still lower in the diabetic group.

We showed that the heart's pumping function is strong, but it is not filling as well as normal between heart beats. This is known as diastolic dysfunction, Pinto said. Although this study did not determine the reason for this, we know that with diabetes, the heart can become stiffer, limiting its ability to stretch and expand.

In addition, images of the femoral artery showed that the flow of blood through the artery was significantly less in the diabetic group during exercise compared with the other two groups.

It appears that irrespective of weight, Type 2 diabetes seems to have a negative effect on the heart and blood vessels in adolescents, Pinto said. This impaired exercise capacity may be reversible with exercise training however, as some literature in adults suggests, but further studies are required to determine this.

Hormone deprivation therapy for prostate cancer may raise diabetes risk

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Men with prostate cancer are at higher risk of developing diabetes or diabetes risk factors if they receive androgen deprivation therapy (ADT) to block the production or action of male hormones that can fuel the growth of this cancer. The results of this new study on the second-most common cancer in men are being presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston.

These patients may benefit from counseling, screening and closer monitoring for the development of these complications, said the study's lead author, Maria Luisa Cecilia Rivera-Arkoncel, MD, a fellow at the Philippine General Hospital in Manila.

This study adds to the scientific evidence that ADT may increase the chance of diabetes. Sometimes called medical or surgical castration, ADT is a common treatment when prostate cancer has spread outside the prostate. It can be permanent by surgically removing both testicles (bilateral orchiectomy), or, more often, temporary by using medications, such as gonadotropin-releasing hormone (GnRH) agonists, to prevent the testes from making testosterone.

In their study, Rivera-Arkoncel and her colleagues compared 38 men with prostate cancer who received ADT and 36 men with less advanced prostate cancer who did not receive hormonal therapy. Men in the ADT group either underwent bilateral orchiectomy at least six months earlier or received six or more months of treatment with injections of GnRH agonists. Both groups received treatment at the Philippine General Hospital from 2004 to 2010. Although the average age of the two groups was not the same at the beginning of the study, the groups were similar in terms of other diabetes risk factors, Rivera-Arkoncel said.

Based on a review of medical records, the researchers identified patients with Type 2 diabetes or the metabolic syndrome. This syndrome is a cluster of metabolic risk factors that increase the chance of developing diabetes, heart disease and stroke. The criteria used for diagnosis include a large waistline plus two of the following: low HDL (good) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood sugar.

Men in the ADT group had a twofold increased probability of having diabetes after ADT, compared with the non-ADT group, Rivera-Arkoncel reported. According to the data, the prevalence of diabetes was 42 percent in the ADT group and 19 percent in the other group. In addition, the group receiving ADT had a higher prevalence of the metabolic syndrome than the non-ADT group did: 37 percent versus 28 percent, respectively.

An increased risk of diabetes with ADT has not previously been demonstrated in the Filipino population, which already has a high prevalence of diabetes, she said.

She cautioned, however, that their cross sectional analytical study suggests, but cannot prove, that ADT is the cause of the increased prevalence of diabetes in men who received this hormonal therapy.

Gene therapy reverses type 1 diabetes in mice

Sat, 04 Jun 2011 04:00:00 PST

( from http://www.rxpgnews.com ) An experimental cure for Type 1 diabetes has a nearly 80 percent success rate in curing diabetic mice. The results, to be presented Saturday at The Endocrine Society's 93rd Annual Meeting in Boston, offer possible hope of curing a disease that affects 3 million Americans.

With just one injection of this gene therapy, the mice remain diabetes-free long term and have a return of normal insulin levels in the body, said Vijay Yechoor, MD, the principal investigator and an assistant professor at Baylor College of Medicine in Houston.

Yechoor and his co-workers used their new gene therapy in a nonobese mouse model of Type 1 diabetes. The therapy attempts to counter the two defects that cause this autoimmune form of diabetes: autoimmune attack and destruction of the insulin-producing beta cells by T cells. First, the researchers genetically engineer the formation of new beta cells in the liver using neurogenin3. This gene defines the development of pancreatic islets, which are clusters of beta cells and other cells. Along with neurogenin3, they give an islet growth factor gene called betacellulin to stimulate growth of these new islets.

The second part of the therapy aims to prevent the mouse's immune system from killing the newly formed islets and beta cells. Previously the research team combined neurogenin3 with the gene for interleukin-10, which regulates the immune system. However, with that gene, they achieved only a 50 percent cure rate in diabetic mice, Yechoor said.

In the new study, the investigators added a gene called CD274 or PD-L1 (programmed cell death 1 ligand-1). It inhibits activity of the T cells only around the new islets in the liver and not in the rest of the body, he explained.

We want the gene to inactivate T cells only when they come to the new islet cells. Otherwise, the whole body would become immunocompromised, Yechoor said.

This treatment reversed diabetes in 17 of 22 mice, or 78 percent. Diabetic mice that otherwise live only six to eight weeks were growing normally and were free of diabetes as long as 18 weeks after injection of the gene therapy, Yechoor said.

This treatment approach, he said, has the potential to be a curative therapy for Type 1 diabetes.

The other mice reportedly responded to the gene therapy initially but then became diabetic again. There are two possibilities, according to Yechoor, why the therapy did not achieve a 100 percent cure rate.

T cells are the predominant part of islet destruction, but other pathways, including beta cells could also contribute, meaning we would need to target those pathways as well, Yechoor said. Or maybe the efficiency of this new protective gene is not sufficient, and we need to give a larger dose.

BD nano pen needle - World's smallest insulin injection needle launched

Wed, 25 May 2011 16:47:19 PST

( from http://www.rxpgnews.com ) The world's smallest pen needle insulin injection for diabetics promising relief from pain was launched here Wednesday, said a statement from its manufacturer Becton, Dickinson and Company -.

'The BD nano pen needle is proven to be as effective as the longer needles in patients of all body types and proven to offer a less painful injection experience for people with diabetes who inject insulin. This is the world's first four mm long pen needle,' said Diwakar Mittal, business manager, BD Medical-Diabetes Care, India.

The needle is four mm in length and of 32 gauge thickness making it the shortest and the thinnest in the market.

Currently, insulin injection needles are available in variable sizes of which the five mm long needles are the most common among diabetics.

'We are confident that this tiny needle can have a big impact by easing diabetes patients' transition and ongoing adherence to injectable drug therapy regimens,' Mittal added.

'The pen needle provides equivalent glucose control as compared to longer insulin pen needles. It effectively delivers an insulin dose to the layer of fat below the skin which is the recommended site for insulin injections,' the statement said.

CHOP partners with Vascular Magnetics, Inc. to pursue commercial potential of blood vessel research

Mon, 09 May 2011 04:00:00 PST

( from http://www.rxpgnews.com ) Building on its extensive laboratory research using magnetically guided nanoparticles to deliver drugs to diseased blood vessels, The Children's Hospital of Philadelphia has just spun off its first startup company, Vascular Magnetics, Inc. (VMI).

By licensing its technology to VMI, a new company formed to develop the lab findings into a commercially viable therapy, the Hospital aims to create a novel, greatly needed treatment for peripheral artery disease (PAD). Characterized by blocked arteries, primarily in the legs, PAD affects more than 27 million older adults in North America and Europe, with diabetes patients and smokers at particularly high risk. Current treatments for PAD, including drug-eluting stents, are ineffective, with re-blockage of the arteries occurring at a high rate.

In addition to being the Hospital's first startup company, the program targets patients outside the Hospital's usual pediatric age group. While our first target group is adult patients, the technique represents a new platform technology, potentially adaptable to delivering a variety of therapies to children as well as adults, says the technology's inventor, Robert J. Levy, M.D., the William J. Rashkind Endowed Chair in Pediatric Cardiology at The Children's Hospital of Philadelphia.

Levy co-founded VMI with Richard S. Woodward, Ph.D., the company's Chief Executive Officer. The two first joined forces through the QED Proof-of-Concept Program sponsored by the University City Science Center in West Philadelphia. The goal of the QED Program, the nation's first multi-institutional proof-of-concept program for life sciences technologies, is to accelerate research from academic laboratories into the marketplace. A unique feature of this program is that academic scientists such as Levy are partnered with experienced business advisors such as Woodward, who has a background that includes developing nanoparticles and polymeric coatings.

The Science Center is proud to have played a role in the launch of Vascular Magnetics, said Stephen S. Tang, Ph.D., MBA, president and CEO of the University City Science Center. VMI's launch is helping to prove our concept that the early addition of business advice is a key element of the tech transfer puzzle.

In a series of animal studies over the past decade, Levy and his team at Children's Hospital have investigated his new approach to stent-based therapy. They have developed nanoparticles, extremely tiny spheres made of a biodegradable polymer impregnated with iron oxide. Under a low-power, uniform magnetic field, much lower than that produced by existing MRI machines, magnetic forces drive the nanoparticles into metal stents and the surrounding artery. The nanoparticles carry a therapeutic payload of the drug paclitaxel, which is released into the surrounding blood vessel tissue in order to slow arterial re-blockage. In 2008, Forbes magazine named Levy's work a promising disruptive technology, one that might eventually supplant conventional technology, in this case, drug-eluting stents.

As they advance the technique to human trials, Levy and Woodward envision a future therapy called Vascular Magnetic InterventionTM which would serve as an adjunct to artery stenting. A physician would open and stent the blocked artery and then insert a catheter tipped with an expandable magnetic targeting device. The targeting device would be expanded against the walls of the artery.

A magnetic field is then applied to the leg, and paclitaxel-containing magnetic nanoparticles would be administered through the catheter. The targeting device develops strong magnetic gradients that force the nanoparticles into the wall of the artery. After treatment and removal of the catheter, the wall of the artery is uniformly coated with the nanoparticles, which slowly biodegrade and release the drug. The uniform coating provides a higher dose of drug than is achievable with a drug-eluting stent. In addition, the technique could be used to re-treat arteries where the stents have become re-blocked.

The technology, said Levy, is highly adaptable. Instead of paclitaxel, it could deliver other therapeutic compounds, DNA for site-specific gene therapy, therapeutic cells, or other treatments. In addition to treating PAD, the technique might carry paclitaxel to narrowed coronary arteries, chemotherapy drugs to a tumor, or other medications to a bile duct or a urinary tract. Eventually, said Levy, the technology could be applied to types of pediatric heart disease, such as primary pulmonary hypertension or heart defects.

As its lab research continues, Vascular Magnetics is moving ahead to attract venture capital. Our plan is to prove the efficacy of this therapy in humans by late 2015, said Woodward. The revenue projections for the company suggest sales of over a billion dollars per year within about four years after commercial launch.

Bariatric surgery highly cost-effective treatment for type 2 diabetes in the obese

Tue, 29 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (March 29, 2011) -- Bariatric surgery is an especially cost-effective therapy for managing Type 2 diabetes in moderately and severely obese patients. These findings and others were presented today at the 2nd World Congress on Interventional Therapies for Type 2 Diabetes, hosted by NewYork-Presbyterian Hospital and Weill Cornell Medical College.

Cost effectiveness is central to the larger issue of access to surgical treatment of diabetes, says Dr. Francesco Rubino, director of the Congress and director of gastrointestinal metabolic surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Today, an estimated 285 million people around the globe suffer from Type 2 diabetes, and the number is expected to double by 2030, notes Dr. Rubino, who also serves as associate professor of surgery at Weill Cornell Medical College. The need for effective, potentially curative therapies is urgent.

According to an analysis presented today at the Congress by an Australian researcher, bariatric surgery to treat Type 2 diabetes has been demonstrated to be very cost effective in the countries in which this research has been done -- the United States, United Kingdom, Australia, and in some European settings.

The review also found that several studies have determined that bariatric surgery was not only cost effective, but cost saving, says Catherine Keating, a senior research fellow from the Health Economics Unit at Deakin University in Melbourne, who made the presentation. For obese patients diagnosed with Type 2 diabetes during the two years prior to bariatric surgery, one study found that the upfront costs of surgery would be fully recouped through the prevention of future health care costs to treat Type 2 diabetes. This study was undertaken alongside a clinical trial that found that remission of Type 2 diabetes was five times greater in surgically treated patients, relative to those receiving conventional therapies, she says.

For this patient group bariatric surgery generates both cost savings and health benefits, Ms. Keating says. This provides the strongest rationale yet for implementation of this treatment on economic grounds.

Treatment studies have shown that bariatric surgery, initially developed for the treatment of morbid obesity, can improve or normalize blood sugar levels, reduce or even eliminate the need for medication, and lower the risk of diabetes-related death.

A number of new cost-effectiveness studies have been discussed at the meeting, says Dr. David Reed Flum, who co-chairs the Congress's policy track. As health care costs soar, the obligation of all those involved in this issue is to understand the way resources are currently being applied to the treatment and prevention of diabetes and to explore what the future impact on health care resources might be if surgery becomes a meaningful part of the public health response to the diabetes epidemic, says Dr. Flum, professor of surgery and health services at the University of Washington School of Medicine.

Health ministers, economists, payers and politicians have a critical role in determining the future of this issue, and we expected a robust dialog during this track of the Congress he says.

The studies looked at whether the costs of the surgery -- estimated at between $15,000 and $24,000 in the United States -- are justified by its effectiveness and its potential to save future health care treatment for obesity-related diseases such as Type 2 diabetes.

The effectiveness credentials for bariatric surgery are now very strong. It has been proven to reduce disease, extend life expectancy and improve quality of life, says Ms. Keating. However, in the context of limited health care budgets, authorities around the world state that health care funding should be informed by an assessment of both treatment costs and effectiveness.

To perform her analysis, Ms. Keating examined 16 published studies that looked at the cost-effectiveness of bariatric surgery, including gastric bypass and gastric banding. Ten of those studies examined the procedures in severely obese patients (those whose body mass index, or BMI, is greater than 35) who did not have Type 2 diabetes, and six looked at patients with Type 2 diabetes whose BMI was 30 to 40 (moderately to severely obese).

Each country establishes its own measure of cost effectiveness. In the United States, the threshold for benefit is $50,000 per quality-adjusted life year (QALY), which is defined as a year of human life with some adjustments for disease or disability.

Ms. Keating's review found that bariatric surgery was very cost effective in both populations she studied (patients without diabetes and a BMI over 35, and patients with diabetes and a BMI 30 to 40), but that it was twice as cost effective in the latter category -- the patients with Type 2 diabetes.

This is likely because patients with diabetes have greater ill heath and therefore more benefits can be achieved through surgery in terms of quality of life, life expectancy and prevention of future health care costs, she says. Without treatment, patients with Type 2 diabetes would endure lifelong disease and escalating health care costs.

Among the costs associated with medical management of Type 2 diabetes are treatment for complications that affect the eyes, heart, kidneys and extremities. Long-term costs include outpatient care, prescription medications and diabetes-related hospitalizations and surgeries, including amputations.

The analysis further demonstrated that using surgery to treat patients with newly diagnosed Type 2 diabetes (diagnosed less than five years before surgery) is more cost effective than using the surgery with patients whose diabetes has been established for longer than five years. For example, a 2009 U.S. study found that bypass surgery had cost-effectiveness ratios of $7,000/QALY and $12,000/QALY for severely obese patients with newly diagnosed and established diabetes, respectively.

Targeting recently diagnosed diabetes is likely to be more cost effective because diabetes remission rates achieved are higher in this group than in those with established Type 2 diabetes, Ms. Keating says. Some of the studies I analyzed, particularly those targeting therapy for patients with recently diagnosed Type 2 diabetes, have found that the costs of surgery may be fully recouped through prevention of future health care costs. This excellent result is fairly rare.

Johns Hopkins scientists link DNA 'end-caps' length to diabetes risk

Thu, 24 Mar 2011 04:00:00 PST

( from http://www.rxpgnews.com ) New evidence has emerged from studies in mice that short telomeres or caps at the ends of chromosomes may predispose people to age-related diabetes, according to Johns Hopkins scientists.

Telomeres are repetitive sequences of DNA that protect the ends of chromosomes, and they normally shorten with age, much like the caps that protect the end of shoelaces. As telomeres shorten, cells lose the ability to divide normally and eventually die. Telomere shortening has been linked to cancer, lung disease, and other age-related illnesses. Diabetes, also a disease of aging, affects as many as one in four adults over the age of 60.

The Johns Hopkins research, described in the March 10 issue of PLoS One, arose from scientist Mary Armanios' observation that diabetes seems to occur more often in patients with dyskeratosis congenita, a rare, inherited disease caused by short telomeres. Patients with dyskeratosis congenita often have premature hair graying and are prone to develop early organ failure.

Dyskeratosis congenita is a disease that essentially makes people age prematurely. We knew that the incidence of diabetes increases with age, so we thought there may be a link between telomeres and diabetes, says Armanios, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Armanios studied mice with short telomeres and their insulin-producing beta cells. Human diabetics lack sufficient insulin production and have cells resistant to its efficient use, causing disruption to the regulation of sugar levels in the blood.

Armanios found that despite the presence of plentiful, healthy-looking beta cells in the mice, they had higher blood sugar levels and secreted half as much insulin as the controls. This mimics early stages of diabetes in humans where cells have trouble secreting insulin in response to sugar stimulus, says Armanios.

Many of the steps of insulin secretion in these mice, from mitochondrial energy production to calcium signaling, functioned at half their normal levels, says Armanios.

In beta cells from mice with short telomeres, they found disregulation of p16, a gene linked to aging and diabetes. No such mistakes were found in the controls.

In addition, many of the gene pathways essential for insulin secretion in beta cells, including pathways that control calcium signaling, were altered in beta cells from mice with short telomeres.

Armanios says that some studies have suggested that diabetic patients may have short telomeres, but it was not clear whether this contributes to diabetes risk or is a consequence of the disease.

Age is the most important risk factor for diabetes, and we also know that family heredity plays a very important role. Telomere length is an inherited factor and may make people more prone to develop diabetes, says Armanios.

Based on this work, Armanios says that telomere length could serve as a biomarker for development of diabetes. Armanios and her colleagues are planning to conduct research to examine whether telomere length can predict the risk of diabetes prospectively.

Trial will test whether surgery is the best option for type 2 diabetes

Thu, 10 Feb 2011 05:00:00 PST

( from http://www.rxpgnews.com ) NEW YORK (Feb. 10, 2011) -- A new clinical trial at NewYork-Presbyterian Hospital/Weill Cornell Medical Center is among the first to test surgery specifically for Type 2 diabetes. The aim of the study is to understand whether surgery can control diabetes, as well or even better than the best medical treatment available today. This is the first study of its kind open to patients who are overweight or mildly obese.

Under current guidelines, bariatric surgery is only indicated for the treatment of severe or morbid obesity, defined as having a body mass index (BMI) of 35 or greater. By contrast, the new study is open to patients with a BMI as low as 26. Normal-weight individuals have BMI ranging between 19 and 25 and overweight individuals have BMI between 26 and 29, whereas a BMI above 30 defines obesity. Patients with a BMI below 26 and above 35 will not be considered for enrollment in the trial.

Previous research has shown that in severely obese patients (BMI greater than 35) gastric bypass surgery is a safe and effective way to treat Type 2 diabetes. It has been shown to improve or normalize blood glucose levels, reduce or even eliminate the need for medication, and lower the risk for diabetes-related death.

There is preliminary evidence suggesting that that these results are attainable even in overweight or mildly-obese patients, says Dr. Francesco Rubino, chief of the gastrointestinal metabolic surgery program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and associate professor of surgery at Weill Cornell Medical College.

In support of this belief, recommendations from the American Diabetes Association's January 2009 issue of Standards of Care: Diabetes Care, and from the Diabetes Surgery Summit Consensus Conference, published in the March 2010 issue Annals of Surgery, suggest that randomized clinical trials for the study of surgery in patients with BMI below 35 are priority for diabetes research.

Having a potentially effective surgical option against diabetes does not mean that surgery is the best choice for every diabetic patient, Dr. Rubino adds. We need rigorous, comparative clinical trials, like this one, in order to better understand when to prioritize surgery and when to recommend traditional medical treatment.

The new study is enrolling 50 patients with Type 2 diabetes who will be randomized to receive surgery -- specifically, Roux-en-Y Gastric Bypass -- or traditional medical therapy and intensive lifestyle modification. All patients will be counseled in lifestyle modification techniques like diet and exercise.

Dr. Rubino expects that there will be medical advantages for patients in both arms of the trial since those assigned to the medical arm will receive the most rigorous medical diabetes therapy available. A multidisciplinary team of diabetes and nutrition experts will take care of patients using the most current, approved drugs for diabetes as well as an intensive approach to lifestyle changes. Patients in the medical arm will also be offered the chance to switch study arms and have surgery free of charge after the study is complete, or earlier should their diabetes remain poorly controlled after medical and lifestyle therapy.

Interaction between fatty acid synthase and nitric oxide synthase key to vascular complications in diabetes mellitus

Sat, 29 Jan 2011 21:46:47 PST

( from http://www.rxpgnews.com ) A key mechanism that appears to contribute to blood vessel damage in people with diabetes has been identified by researchers at Washington University School of Medicine in St. Louis.

Microvascular and macrovascular complications are common in Diabetes mellitus. Many of the nearly 26 million Americans with the disease face the prospect of amputations, heart attack, stroke and vision loss because of damaged vessels.

Reporting in the Journal of Biological Chemistry, the Washington University researchers say studies in mice show that the damage appears to involve two enzymes, fatty acid synthase (FAS) and nitric oxide synthase (NOS), that interact in the cells that line blood vessel walls.

“We already knew that in diabetes there’s a defect in the endothelial cells that line the blood vessels,” says first author Xiaochao Wei, PhD. “People with diabetes also have depressed levels of fatty acid synthase. But this is the first time we’ve been able to link those observations together.”

Wei is a postdoctoral research scholar in the lab of Clay F. Semenkovich, MD, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and chief of the Division of Endocrinology, Metabolism and Lipid Research.

Wei studied mice that had been genetically engineered to make FAS in all of their tissues except the endothelial cells that line blood vessels. These so-called FASTie mice experienced problems in the vessels that were similar to those seen in animals with diabetes.

“It turns out that there are strong parallels between the complete absence of FAS and the deficiencies in FAS induced by lack of insulin and by insulin resistance,” Semenkovich says.

Comparing FASTie mice to normal animals, as well as to mice with diabetes, Wei and Semenkovich determined that mice without FAS, and with low levels of FAS, could not make the substance that anchors nitric oxide synthase to the endothelial cells in blood vessels.

“We’ve known for many years that to have an effect, NOS has to be anchored to the wall of the vessel,” Semenkovich says. “Xiaochao discovered that fatty acid synthase preferentially makes a lipid that attaches to NOS, allowing it to hook to the cell membrane and to produce normal, healthy blood vessels.”

In the FASTie mice, blood vessels were leaky, and in cases when the vessel was injured, the mice were unable to generate new blood vessel growth.

The actual mechanism involved in binding NOS to the endothelial cells is called palmitoylation. Without FAS, the genetically engineered mice lose NOS palmitoylation and are unable to modify NOS so that it will interact with the endothelial cell membrane. That results in blood vessel problems.

Semenkovich
“In animals that don’t have fatty acid synthase and normal nitric oxide synthase in endothelial cells, we saw a lot of leaky blood vessels,” Semenkovich explains. “The mice also were more susceptible to the consequences of infection, and they couldn’t repair damage that occurred — problems that also tend to be common in people with diabetes.”

In one set of experiments, the researchers interrupted blood flow in the leg of a normal mouse and in a FASTie mouse.

“The control animals regained blood vessel formation promptly,” Semenkovich says, “but that did not happen in the animals that were modified to be missing fatty acid synthase.”

It’s a long way, however, from a mouse to a person, so the researchers next looked at human endothelial cells, and they found that a similar mechanism was at work.

“Our findings strongly suggest that if we can use a drug or another enzyme to promote fatty acid synthase activity, specifically in blood vessels, it might be helpful to patients with diabetes,” Wei says. “We also have been able to demonstrate that palmitoylation of nitric oxide synthase is impaired in diabetes, and if we can find a way to promote the palmitoylation of NOS, even independent of fatty acid synthase, it may be possible to treat some of the vascular complications of diabetes.”

And it shouldn’t matter whether a person has type 1 diabetes and can’t manufacture insulin or the more common type 2 diabetes, in which a person becomes resistant to insulin.

“That’s one of the key findings,” Semenkovich says. “It won’t matter whether it’s an absence of insulin or resistance to insulin: both are associated with defects in FAS.”

Silencing the TLR4 gene to stop the cardiovascular disease in diabetic patients

Fri, 10 Dec 2010 08:11:49 PST

( from http://www.rxpgnews.com ) Silencing the TLR4 gene can stop the process which may lead to cardiovascular disease in diabetic patients. Researchers writing in BioMed Central's open access Journal of Translational Medicine carried out a series of in vitro tests which demonstrated that TLR4 plays a critical role in hyperglycaemic cardiac apoptosis, and that silencing the gene using specific small interfering RNA (siRNA) can prevent it.

Wei-Ping Min, from the University of Western Ontario, Canada, worked with a team of researchers to perform the tests in cells taken from diabetic mice. He said, "We found that TLR4 was up-regulated in the myocardia of diabetic mice. Treatment with TLR4 siRNA attenuated the apoptosis seen in these cells, thus highlighting the potential clinical use of siRNA-based therapy".

Min and his colleagues induced hyperglycemia in adult mice by injecting them with streptozotocin, a toxin that poisons insulin-producing beta cells. They found that after 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated, and signs of apoptosis were evident. Silencing TLR4 resulted in suppression of apoptotic cascades. According to Min, "This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene".

Patients receiving dialysis are at a heightened risk for sudden cardiac death

Sun, 14 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Approximately 500,000 Americans require dialysis to treat kidney disease; of that population nearly half of the deaths that occur are caused by cardiovascular disease. Dialysis patients are at elevated risk for sudden cardiac death, but physicians are unclear why these deaths occur because little research has been done to examine how to best manage heart disease in this high-risk population.

Northwestern Medicine cardiologist Rod Passman, MD, medical director for the Center for Atrial Fibrillation at the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital will present a paper at the American Heart Association's Scientific Sessions being held November 13 through 17 in Chicago about sudden cardiac death in dialysis patients. Passman is working to increase understanding within the medical community about this heightened mortality risk and how to prevent sudden cardiac death among this rapidly growing patient population.

Dialysis patients have extraordinarily high mortality rates with cardiac disease accounting for 43 percent of deaths in this population; data indicates that approximately 27 percent of the mortalities are due to sudden cardiac death, said Passman, who is also an associate professor of cardiology at Northwestern University's Feinberg School of Medicine. Patients on dialysis are excluded from clinical trials examining sudden cardiac death because of their kidney disease. The lack of research complicates clinicians' ability to understand the connection between renal disease and cardiovascular disease. The medical community needs to stop neglecting this community of patients because it is a rapidly growing group.

Sudden cardiac death is unexpected natural death from a cardiac cause within a short time period, generally less than an hour from the onset of symptoms in a person without prior condition that would appear fatal. In most cases, sudden cardiac death occurs because of ventricular arrhythmias (abnormal heart rhythms), including ventricular tachycardia (VT) or ventricular fibrillation (VF).

Risk of cardiac arrest in dialysis patients is related to age and dialysis duration, said Passman. A study by the United States Renal Disease Data System (USRDS) indicates longer dialysis duration is associated with higher mortality. This data also leads us to believe that end-stage renal disease is a primary promoter of cardiac disease and increased risk for sudden cardiac death.

By analyzing USRDS data, Passman and other researchers are beginning to better understand how cardiovascular disease affects renal patients and developing plans for preventing sudden cardiac death. The more understanding we gain in regards to why these patients are dying from sudden cardiac death, the better chance we have to save them, Passman explained. The best methods for prevention are medicinal options, including beta-adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin type II receptor blockers (ARB), or both external and implantable defibrillators.

Data also indicates a connection between potassium levels in a patient's dialysate prescription and sudden cardiac death. Patients who suffered a cardiac arrest during dialysis were twice as likely to be on low-potassium dialysate versus higher levels of potassium, which were associated with the best survival rates. According to Passman, clinicians should evaluate and modify dialysate prescription on an ongoing basis in an effort to minimize risk of sudden cardiac death.

By highlighting the issue of sudden cardiac death in dialysis patients, Passman hopes that he and other physicians will be able to better understand this unique patient population. There is very little research related to prevention of sudden cardiac death in dialysis patient; this group remains a mystery in terms of medical research, even though their numbers are growing, said Passman. The lack of research and study of cardiovascular disease in kidney patients is a problem that must be addressed. By understanding why dialysis patients are at such great risk for sudden cardiac death, we can begin to develop better standards for prevention.

JDRF clinical panel recommends next steps for artificial pancreas clinical testing

Wed, 10 Nov 2010 05:00:00 PST

( from http://www.rxpgnews.com ) Diabetes experts at a meeting convened by the U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) took the next step in advancing efforts toward the development of an artificial pancreas: putting forth clinical recommendations to ensure the safe and effective testing of artificial pancreas technology in real-life situations. We are pleased at today's meeting there was a strong consensus among leading clinicians, researchers and industry leaders regarding the path toward outpatient studies for both low-glucose suspend and artificial pancreas systems.

Even with treatments available today, tight blood sugar control remains a challenge and daily struggle for those living with type 1 diabetes. In fact, the majority of people living with the disease are not achieving recommended target levels. An artificial pancreas, essentially a device that would both measure blood sugar and dispense appropriate amounts of insulin to keep levels in optimal range, would take much of the guesswork out of daily management of the disease, said Dr. Aaron Kowalski, Assistant Vice President of Treatment Therapies at JDRF. In the long-run, controlled blood sugar levels will help to lessen or avert the devastating complications from type 1 diabetes.

To date, artificial pancreas devices have been successfully tested in controlled inpatient or hospital settings, demonstrating the potential for this technology to improve blood sugar control. Now it must be tested safely in real-world conditions. And clear and reasonable regulatory guidelines must be established to ensure that the upcoming studies advance the technology to reach patients as soon as possible.

We believe a safe and effective first generation artificial pancreas system is possible with today's technology, even as we continue to encourage development of improved devices. Experts at today's FDA workshop outlined a clear path forward to safely speed the development and delivery of artificial pancreas systems to patients, said Jeffrey Brewer, President and CEO of JDRF.

To help advance these efforts, JDRF formed a Clinical Panel of internationally renowned leaders in the diabetes field to make recommendations to FDA on key clinical steps and issues critical to the advancement of studies of these systems outside of the hospital. Panel members speaking at today's workshop included David Nathan, Director, Clinical Research Center and Diabetes Center at Massachusetts General Hospital and Professor of Medicine, Harvard Medical School; and William Tamborlane, Professor and Chief of Pediatric Endocrinology and Diabetes, Yale University School of Medicine.

The panel developed a series of clinical recommendations that were shared at today's meeting. They were based on key areas addressed by the FDA, NIH, JDRF, clinicians and industry. First, the recommendations addressed questions on how should studies on artificial pancreas systems move safely from inpatient (hospital) settings to outpatient (real-world) testing. Second, the panel identified which subset of patients should be considered when testing artificial pancreas systems. The third area focused on how to ensure the safety of patients participating in the studies and eventually for everyday use. Lastly, the panel identified what outcomes should be measured in studies to demonstrate the safety and effectiveness of the device.

A summary of the panel's recommendations is available here. A full report by the panel will be forthcoming.

According to panel chair Robert Sherwin, M.D., Yale University, The panel believes, with certain safeguards, artificial pancreas systems can be safely tested in real world settings.

The incidence of type 1 diabetes is on the rise. Today's tools to manage the disease are insufficient. We have the technology at our disposal to make an artificial pancreas work. Now it's time to move forward quickly to define the regulatory pathway so final studies can be completed and better technologies can be made available to adults and children struggling with this difficult disease, added Mr. Brewer.

Gastric bypass alters sweet taste function

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Gastric bypass surgery decreases the preference for sweet-tasting substances in obese rats, a study finding that could help in developing safer treatments for the morbidly obese, according to Penn State College of Medicine researchers.

Roux-en-Y gastric bypass surgery is the most common effective treatment for morbid obesity, said Andras Hajnal, M.D., Ph.D., associate professor, Department of Neural and Behavioral Science and Surgery. Many patients report altered taste preferences after having the procedure.

This surgery involves the creation of a small gastric pouch and bypassing a portion of the upper small intestine. Unlike other weight-reduction methods, it produces substantial and durable weight loss and significant improvements in obesity-related medical conditions including diabetes.

Study results in obese rats suggest that post-surgery changes in the gastrointestinal anatomy affect change in the brain that relate to taste.

Obese rats given gastric bypass surgery showed a reduced preference for high concentration sucrose water when compared to obese rats that did not have surgery. Researchers observed a similar decrease in preference with other sweet-tasting substances, but not for salty, sour or bitter substances. Researchers observed no change in preference in lean rats that had gastric bypass surgery.

The obese rats used do not have the ability to produce the receptor for feeling satiated shortly after a meal because they lack the gut hormone CCK-1. As a result, these rats consumed larger meals and, over time, became obese and developed type-2 diabetes. Interestingly, previous studies lead by the Penn State investigators found an increased sweet preference in these rats, which is also often seen in people struggling with weight management.

It appears that an uncontrolled appetite may get further boost from altered taste functions during development of obesity and diabetes, Hajnal said. How much of this vicious circle is due to changes in the neurons inside the brain, which receive taste sensations from the tongue and report to the higher order motivational brain centers, we don't know.

The researchers recorded the activity of 170 taste-responsive neurons in the brain. These showed a shift in the neurons' firing activity similar to the behavioral response, which was measured in lick rates of the rats within a ten-second time period. Neurons in the obese rats' brain responded more vigorously to higher-concentration sucrose water placed on the tongue when compared to lean rats. These effects were reversed by gastric bypass surgery and matched the response of lean rats -- a preference for lower concentration sucrose.

The rats that had gastric bypass surgery lost weight comparable to humans who received the surgery -- 26 to 30 percent of their weight -- and maintained the loss for a long period of time after surgery. Following surgery, the obese rats also showed a higher tolerance for glucose, indicating improvement in diabetes.

This supports the applicability of this rat model of Roux-en-Y gastric bypass to humans and also suggests that the observed taste changes following the surgery were not related to 'human factors' such as awareness and compliance to dietary and behavioral interventions, Hajnal said.

The researchers published their findings in the October issue of the

Liver hormone is a cause of insulin resistance

Tue, 02 Nov 2010 04:00:00 PST

( from http://www.rxpgnews.com ) Researchers have identified a hormone produced and secreted by the liver as a previously unknown cause of insulin resistance. The findings, in the November issue of Cell Metabolism, a Cell Press publication, suggest a new target for the treatment of insulin resistance and type 2 diabetes, the researchers say.

The current study sheds light on a previously underexplored function of the liver; the liver participates in the pathogenesis of insulin resistance through hormone secretion, said Hirofumi Misu of Kanazawa University Graduate School of Medical Science in Japan.

The researchers had discovered earlier that genes encoding secretory proteins are abundantly expressed in the livers of people with type 2 diabetes. On the basis of those findings, Misu and colleagues began to suspect that, similar to the role of fat tissue, the liver might contribute to the development of type 2 diabetes and insulin resistance via secretory proteins they call hepatokines.

Now, the researchers report the results of comprehensive gene expression analyses, revealing that the liver expresses higher levels of the gene encoding selenoprotein P (SeP) in people with type 2 diabetes who are more insulin resistant. Blood levels of SeP are also increased in people with diabetes compared to healthy people.

Further studies in mice added support to the notion that the connection between SeP and insulin resistance is causal. When the researchers gave normal mice SeP, they became insulin resistant and their blood sugar levels rose. A treatment that blocked the activity of SeP in the livers of diabetic and obese mice improved their sensitivity to insulin and lowered blood sugar levels.

Misu said that SeP was known previously as a protein produced mainly in the liver, where it transports the essential trace element selenium from the liver to other parts of the body. But the protein's clinical significance and, more specifically, its role in glucose homeostasis weren't known.

In the development of insulin resistance, the researchers don't think SeP acts on its own. It is well known, they explain, that fat tissue is a main contributor to the development of insulin resistance by producing fat-derived hormones called adipokines. But they say they have preliminary evidence for a connection between SeP and adipokine production, which will be the subject of further investigation.

The new findings suggest that there may be other hormones derived from the liver with important and varied roles in the body, Misu and his colleague Toshinari Takamura add. Our study raises the possibility that the liver functions as an endocrine organ by producing a variety of hepatokines and that the dysregulation or impairment of hepatokine production might contribute to the development of various diseases.

Can Wii help control gestational diabetes?

Wed, 13 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) TORONTO, Ont., Oct. 13, 2010--Many women have trouble finding time to exercise in their busy lifestyles. That's especially true for pregnant women who live in northern climates such as Canada, where the weather can limit outdoor activity during winter months every year.

But exercise is critical to managing gestational diabetes, a growing problem that occurs in 2 to 9 per cent of pregnancies.

Researchers at St. Michael's Hospital have proposed a novel solution. They want to offer women recently diagnosed with gestational diabetes a Nintendo Wii gaming console, a Wii Fit activity platform and two activity-promoting games, Wii Sport and Wii Fit Plus. The goal is to see whether the women get more exercise and thereby lower their blood glucose levels and decrease the need for insulin.

We all know how hard it is to maintain a proper exercise regimen in the best of times. It is obviously much harder while pregnant. We thought that by combining a fun, home-based activity with a clinical goal we will be able to achieve an important health benefit for our patients with gestational diabetes, said Dr. Howard Berger, head of the high-risk pregnancy unit at St. Michael's.

Women usually have a blood test for gestational diabetes when they are 24 to 28 weeks pregnant. The treatment is diet and exercise, such as 20-30 minutes of walking a day. If that doesn't control their blood glucose levels, they have to take insulin, which happens in 15 to 66 per cent of women with gestational diabetes.

Women with gestational diabetes are at increased risk of developing diabetes and obesity later in life. They are also at increased risk of developing complications during pregnancy and delivery, including heavier babies, pre-eclampsia, premature births, higher rates of Cesareans and post-partum hemorrhage. Newborns of a diabetic mother may also suffer from metabolic complications including hypoglycemia (low blood glucose) and hyperinsulinemia, a condition also known as pre-diabetes.

Study participants will be patients at the hospital's diabetes in pregnancy clinic, part of the Women's Health Centre, which today moves back to 61 Queen St. E. following a $6.3 million renovation of their fourth- and fifth-floor offices and exam room and the building lobby.

Our new ambulatory center for women strives to treat women as a whole, offering the most appropriate care for their individual situation and incorporating the most recent advances in health care practice and technology, said Dr. Guylaine Lefebvre, chief of obstetrics and gynecology.

The renovations include bigger examining rooms, where the patient will remain while various health care professionals come to her, and bigger ultrasound rooms, with space for partners and relatives to be present. The architect for the project was from Diamond + Schmitt Architects, who also designed the hospital's new Li Ka Shing Knowledge Institute.

Heart, kidney, diabetes and cancer MEP groups league against chronic disease to seek European commitment

Tue, 05 Oct 2010 04:00:00 PST

( from http://www.rxpgnews.com ) In an unprecedented effort to bring prevention of chronic diseases to the top of the EU agenda, the MEP Heart Group , the MEP Group for Kidney Health , the EU Diabetes Working Group and MEPs Against Cancer organise a joint meeting today in the European Parliament, together with representatives of health professionals and health activists at European level.

If we don't address these chronic diseases urgently, they threaten the Europe 2020 strategy, especially the goal to have 75% of the working population employed and productive says Linda McAvan, MEP and co-chair of the MEP Heart Group. Most of these chronic diseases are treatable but not curable, which explains why they generate an enormous financial burden due to treatment and care costs and loss of economic productivity.

Chronic diseases are largely preventable and in this respect the European Parliament has a major role to play says Frieda Brepoels, chair of the MEP Group for Kidney Health.

In a joint statement issued at the end of the meeting, MEPs call upon the competent authorities in the member states to urgently develop and improve policies aiming at tackling chronic diseases. A higher investment in prevention is needed, continues Frieda Brepoels, in particular by raising awareness about common risk factors and promoting healthy lifestyles.

Four major health determinants - tobacco, poor diet, alcohol and lack of physical activity - account for most chronic illness and death in Europe. Addressing chronic diseases will allow Europeans to live longer and healthier lives, stay longer in the workforce and contribute to reversing the alarming negative labour force growth which is predicted for 2020.

High tobacco and alcohol taxes, smoke free environment, good nutrition labelling which helps consumers make healthy choices and measures to prioritise the needs of pedestrians and cyclists over those of motorists in urban areas are but some of the few measures that politicians should put in place.

Alojz Peterle, Member of the European Parliament and President of MEPs Against Cancer (MAC), one of the co-organisers of the event said: 'We urge MEPs, the European Commission, the Council of Ministers and national governments to work together to tackle the problem of chronic diseases. It is only by working in partnership that we will be able to put in place effective Europe-wide policies aimed at preventing these conditions that cause so much suffering and death each year. Prevention is undoubtedly cheaper than disease management and treatment and, therefore, it makes economic sense to pursue these policies now at a time when many national governments are having to curb their expenditure.'

Aerobic exercise relieves insomnia

Wed, 15 Sep 2010 04:00:00 PST

( from http://www.rxpgnews.com ) CHICAGO --- The millions of middle-aged and older adults who suffer from insomnia have a new drug-free prescription for a more restful night's sleep. Regular aerobic exercise improves the quality of sleep, mood and vitality, according to a small but significant new study from Northwestern Medicine.

The study is the first to examine the effect of aerobic exercise on middle-aged and older adults with a diagnosis of insomnia. About 50 percent of people in these age groups complain of chronic insomnia symptoms.

The aerobic exercise trial resulted in the most dramatic improvement in patients' reported quality of sleep, including sleep duration, compared to any other non-pharmacological intervention.

This is relevant to a huge portion of the population, said Phyllis Zee, M.D., director of the Sleep Disorders Center at Northwestern Medicine and senior author of a paper to be published in the October issue of Sleep Medicine. The lead author is Kathryn Reid, research assistant professor at Feinberg.

Insomnia increases with age, Zee said. Around middle age, sleep begins to change dramatically. It is essential that we identify behavioral ways to improve sleep. Now we have promising results showing aerobic exercise is a simple strategy to help people sleep better and feel more vigorous.

The drug-free strategy also is desirable, because it eliminates the potential of a sleeping medication interacting with other drugs a person may be taking, Reid said.

Sleep is an essential part of a healthy lifestyle, like nutrition and exercise, noted Zee, a professor of neurology, neurobiology, and physiology at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital.

By improving a person's sleep, you can improve their physical and mental health, Zee said. Sleep is a barometer of health, like someone's temperature. It should be the fifth vital sign. If a person says he or she isn't sleeping well, we know they are more likely to be in poor health with problems managing their hypertension or diabetes.

The study included 23 sedentary adults, primarily women, 55 and older who had difficulty falling sleep and/or staying asleep and impaired daytime functioning. Women have the highest prevalence of insomnia. After a conditioning period, the aerobic physical activity group exercised for two 20-minute sessions four times per week or one 30-to-40-minute session four times per week, both for 16 weeks. Participants worked at 75 percent of their maximum heart rate on at least two activities including walking or using a stationary bicycle or treadmill.

Participants in the non-physical activity group participated in recreational or educational activities, such as a cooking class or a museum lecture, which met for about 45 minutes three to five times per week for 16 weeks.

Both groups received education about good sleep hygiene, which includes sleeping in a cool, dark and quiet room, going to bed the same time every night and not staying in bed too long, if you can't fall asleep.

Exercise improved the participants' self-reported sleep quality, elevating them from a diagnosis of poor sleeper to good sleeper. They also reported fewer depressive symptoms, more vitality and less daytime sleepiness.

Better sleep gave them pep, that magical ingredient that makes you want to get up and get out into the world to do things, Reid said.

The participants' scores on the Pittsburgh Sleep Quality Index dropped an average of 4.8 points. (A higher score indicates worse sleep.) In a prior study using t'ai chi as a sleep intervention, for example, participants' average scores dropped 1.8 points.

Exercise is good for metabolism, weight management and cardiovascular health and now it's good for sleep, Zee said.

Science leaders urge diabetes patients to talk with doctor before making changes to medication use

Thu, 15 Jul 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The Endocrine Society, American Diabetes Association and American Association of Clinical Endocrinologists issue joint statement in response to an FDA panel's recommendation to keep rosiglitazone (Avandia) on the market

The U.S. Food and Drug Administration's (FDA) Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee has completed their evaluation of the scientific research available on the safety of rosiglitazone. The deliberations of the panel reflected the complexity of the issues, with several members voting to add additional warnings or to withdraw the drug from the U.S. market. Ultimately, the final recommendation was to allow Avandia to remain on the market. Now that the expert panel has concluded its meeting, the FDA will review their recommendations and make the final decision on whether the drug remains available to patients.

Even with the panel's recommendation, the amount of scrutiny the drug has received may lead some diabetes patients who currently take rosiglitazone to want to stop taking the drug. The Endocrine Society, American Diabetes Association and the American Association of Clinical Endocrinologists urge patients to not make any changes to their medication use without discussing their treatment with their physician.

Patients should continue taking all currently prescribed medications unless instructed otherwise by their health care provider, said Dr. Robert A. Vigersky, immediate Past President of The Endocrine Society. Stopping diabetes medications can cause significant harm and result in higher levels of blood glucose that may cause severe short term health problems and could increase the risk of diabetes-related complications in the long term.

The worst outcome would be to not treat diabetes properly, thereby risking its complications, said Dr. Daniel Einhorn, President of the American Association of Clinical Endocrinologists. This unintended consequence has happened with past inquiries into diabetes medications, and we very much want to avoid it happening again.

Reports regarding the cardiovascular safety of rosiglitazone have not been definitive. While some analyses have suggested an increased cardiovascular risk with use of the diabetes drug others have not shown substantial evidence of such an association.

Patients should be aware that regardless of the opinion and decisions on rosiglitazone, there are numerous drugs available to maintain glucose control in people with type 2 diabetes. Patients should discuss these options with their health care providers, said Dr. Richard Bergenstal, President, Medicine and Science, American Diabetes Association.

Following any decision from the FDA, The Endocrine Society, The American Diabetes Association and the American Association of Clinical Endocrinologists will provide detailed information interpreting FDA action for both health care professionals and patients with diabetes.

Study finds no link between diabetes drug rosiglitazone and increased rate of heart attack

Tue, 29 Jun 2010 04:00:00 PST

( from http://www.rxpgnews.com ) The diabetes drug rosiglitazone has been under intense scrutiny since a 2007 study in the New England Journal of Medicine looked at more than 40 clinical trials and linked the drug's use with increased risk of heart attack and death from heart disease.

Now, in a post-trial analysis of results from an international clinical trial of 2,368 diabetes patients with cardiovascular disease, researchers at Washington University School of Medicine in St. Louis and several major centers across the country report no increased rate of heart attack or death in patients taking rosiglitazone. In fact, this analysis found a lower combined rate of death, heart attack and stroke associated with patients taking rosiglitazone compared with those who were not taking a thiazolidinedione drug (rosiglitazone or pioglitazone).

Richard G. Bach, MD, a Washington University researcher and medical director of the Cardiac Intensive Care Unit at Barnes-Jewish Hospital, presented this research June 29 in a late-breaking clinical studies session at the American Diabetes Association's Scientific Sessions in Orlando, Fla.

These new results are relevant in the debate over rosiglitazone's cardiovascular safety, according to Bach. In an advisory panel scheduled to meet next month, the U.S. Food and Drug Administration (FDA) will reassess the safety of rosiglitazone and determine whether it should remain on the market.

As a result of the questions raised by the meta-analysis in the New England Journal and certain other studies, some have cautioned that rosiglitazone should not be used in patients with coronary heart disease and diabetes, says Bach, also associate professor of medicine in the Cardiovascular Division at the School of Medicine. Our data carefully examine use of rosiglitazone in a large cohort of patients with established coronary artery disease and suggest that treatment with rosiglitazone was not associated with an increased risk of ischemic cardiovascular events, like heart attack and stroke, and in a number of analyses it was associated with a lower rate of those events, he says.

Rosiglitazone, made by GlaxoSmithKline under the brand name Avandia, is an insulin-sensitizing drug. In type 2 diabetes, the pancreas continues to make insulin, but the body's tissues can't use it well. Rosiglitazone and other thiazolidinediones (TZDs) do not provide more insulin but reduce insulin-resistance, helping the body regulate blood sugar with the insulin it already makes.

Rosiglitazone was one of several drugs used to control blood sugar in the BARI 2D clinical trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes). Between 2001-08, BARI 2D was a multi-center trial directed by the University of Pittsburgh that investigated treatment strategies for patients with both type 2 diabetes and cardiovascular disease. The trial was designed to determine the best strategies for treating patients with both conditions.

To address their cardiovascular disease, patients in BARI 2D were randomly assigned to receive either intensive medical therapy plus revascularization treatment (such as angioplasty or bypass surgery) or intensive medical therapy alone (with the possibility of revascularization treatment later if their symptoms did not improve).

To address their diabetes, the same patients were randomly assigned to receive either insulin-providing drugs (such as insulin itself) or insulin-sensitizing drugs (such as rosiglitazone or another drug, metformin). As a result, a large number of patients were treated with rosiglitazone during approximately five years of follow up in the trial. This aspect of BARI 2D provided a way to investigate rosiglitazone's cardiovascular safety after it came under scrutiny in 2007. In addition, Bach notes the importance of this new analysis because it looks at a population of patients already at high risk of cardiovascular events like heart attack and stroke.

Compared with patients not receiving a TZD, those who did take rosiglitazone showed a 28 percent lower combined rate of death, heart attack and stroke. In addition, the rate of stroke on its own was 64 percent lower in patients receiving rosiglitazone. Both of these differences were statistically significant. Rates of heart attack and death on their own showed no significant difference between those who took rosiglitazone and those who did not. In line with other studies, rosiglitazone was associated with increased risk of bone fracture, especially in women.

While these results support rosiglitazone's safety in patients with existing heart disease, Bach points out a weakness in the new analysis. Because BARI 2D was designed to assess treatment strategies, not the safety of rosiglitazone, the drug was not randomly assigned. It was the treating physician who decided whether to prescribe rosiglitazone to a particular patient, in line with the study protocol.

Rapid-acting insulin in inhaled form

Tue, 23 Mar 2010 10:40:52 PST

( from http://www.rxpgnews.com ) Scientists today described a new ultra-rapid acting mealtime insulin (AFREZZA™) that is orally inhaled for absorption via the lung. Because the insulin is absorbed so rapidly, AFREZZA's profile closely mimics the normal early insulin response seen in healthy individuals. AFREZZA is awaiting approval by the U. S. Food and Drug Administration (FDA). This presentation took place at the 239th American Chemical Society National Meeting, being held here this week.

Andrea Leone-Bay, Ph.D. and colleagues at MannKind Corporation said that the new insulin product, uses the Technosphere® technology, a delivery technology that is applicable to a wide variety of other drugs that are currently injected. Like insulin, these medications are proteins that would be digested and destroyed in the stomach if taken by mouth.

One such product, MKC-180, is a Technosphere® formulation of a natural hormone that controls appetite and is under investigation as a therapy for obesity using pulmonary delivery. "In nonclinical studies remarkable reductions in food intake have been observed," Leone-Bay said. MannKind is also evaluating Technosphere® technology with drugs that treat pain and osteoporosis.

"Our proprietary Technosphere® Technology platform is based on particles formed by the self-assembly of a small molecule," Leone-Bay explained. "Drugs can be loaded onto these particles, which are then dried to form a dry powder. Using a thumb-sized device, patients inhale a small amount of the powder, roughly equivalent to a pinch of salt. This powder dissolves immediately after inhalation and the drug is absorbed into the patient's bloodstream. Most importantly, the drug is absorbed ultra-rapidly so it becomes effective much more quickly than an injection of the same drug. For some drugs, ultra-rapid systemic delivery provides distinct clinical advantages over injection, including profiles that match the body's natural responses in processes like hormone secretion."

AFREZZA™ (insulin human rDNA origin) Inhalation Powder is an ultra-rapid acting insulin intended for use at mealtime to control the rapid rise in blood sugar levels that occurs in people with diabetes immediately after a meal. At other times, people with diabetes would take injections of other kinds of insulin.

Leone-Bay said AFREZZA™ controls glucose as well as current state-of-the-art treatments, poses a lower risk of hypoglycemia than that typically associated with mealtime insulin therapy, and leads to less weight gain compared to other insulin treatments," according to Leone-Bay. "Additionally, and importantly, AFREZZA™ provides the unique benefit of a small, discreet, and easier-to-use inhalation device."

Frequent napping associated with an increased prevalence of type 2 diabetes

Mon, 01 Mar 2010 13:24:48 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 05:00:00 PST

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

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

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

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

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

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

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

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

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

Sat, 06 Feb 2010 12:48:53 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Thu, 29 Oct 2009 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

Obesity expert named Life Scientist of the Year

Wed, 28 Oct 2009 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

ERC Starting Grant for the researcher of kidney diseases

Fri, 11 Sep 2009 04:00:00 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 03:59:36 PST

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

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

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

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

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

Scarring key to link between obesity and diabetes

Thu, 13 Aug 2009 04:00:00 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 16:11:56 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 04:00:00 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Thu, 11 Jun 2009 04:00:00 PST

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

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

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

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

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

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

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

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

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

Gene triggers for diabetes found

Wed, 13 May 2009 14:54:57 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Gene therapy appears safe to regenerate gum tissue

Tue, 07 Apr 2009 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

Team-based diabetes care fetches more value for dollar

Thu, 26 Feb 2009 05:00:00 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 00:30:27 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 05:00:00 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 01:54:58 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 13:53:26 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 05:00:00 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 05:00:00 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 05:00:00 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 05:00:00 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 05:00:00 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

Fri, 19 Sep 2008 04:00:00 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 04:00:00 PST

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

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

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

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

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

Presidential medal for technological breakthroughs earned by 2 chemical engineering professors

Wed, 27 Aug 2008 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

Mon, 21 Jul 2008 23:23:18 PST

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

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

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

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

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

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

Racial disparities exist among diabetes patients treated by the same physician

Mon, 09 Jun 2008 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

Fri, 30 May 2008 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 10:12:00 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 06:57:23 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 07:22:07 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 05:00:00 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 05:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fri, 22 Feb 2008 05:00:00 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 23:40:00 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 14:07:29 PST

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

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

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

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

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

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

Oral anti diabetic substance discovered

Mon, 24 Dec 2007 05:00:00 PST

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

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

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

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

Stanford researchers shed light on black box of gestational diabetes

Thu, 01 Nov 2007 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Low doses of a red wine ingredient fight diabetes in mice

Tue, 02 Oct 2007 04:00:00 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Joslin researchers uncover potential role of leptin in diabetes

Mon, 01 Oct 2007 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

Mon, 17 Sep 2007 04:00:00 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 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Thu, 06 Sep 2007 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

Wed, 05 Sep 2007 04:00:00 PST

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

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

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

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

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

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

Environmental stress probed in cardiovascular disease, diabetes

Wed, 05 Sep 2007 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Wed, 05 Sep 2007 04:00:00 PST

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

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

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

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

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

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

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

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

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

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

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

Sun, 02 Sep 2007 04:00:00 PST

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

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

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

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

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

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

Treating diabetes during pregnancy can break link to childhood obesity

Tue, 28 Aug 2007 04:00:00 PST

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

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

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

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

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

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

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

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

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

�The obesity risk of children whose mothers had the highest blood sugar levels�and were treated for gestational diabetes�was not statistically different than children of mothers with normal blood sugar levels. This suggests that the 'metabolic imprinting' for childhood obesity that results from gestational diabetes in pregnant women may be reversible, Hillier said.

Novel method enables genomic screening of blood vessels from patient tissue

Tue, 28 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) COLUMBUS, Ohio � Scientists have developed a new method of capturing a complete genome-wide screening of blood vessel cells in their actual disease state, advancing the potential for genetic research on the tissue responsible for delivering nourishment that can accelerate the growth of both a cancer tumor or wound healing.

The method is not just a bonus for translational research, but also has made it possible to determine that genes long associated only with cancer are also expressed in chronic wounds.

The team of scientists, based at Ohio State University Medical Center, is using laser capture microdissection to pluck blood vessels, or if need be a single cell, from human wound tissue as part of a major research initiative looking for mechanisms underlying chronic wounds.

They published a description of the research method in the Proceedings of the National Academy of Sciences scheduled for online publication this week and print publication on Sept. 4.

�We have enabled the capture and genome-wide screening of blood vessels from biopsy material regardless of disease,� said Dr. Chandan Sen, executive director of Ohio State�s Comprehensive Wound Center and senior author of the paper. �It�s a big leap in our ability to perform high-resolution vascular biology research utilizing patient material.�

The method is superior to previous methods of cell biology research because it allows scientists to study clinical tissue material with cell-specific resolution, said Sen, also professor and vice chair of surgery and deputy director of Ohio State�s Davis Heart and Lung Research Institute. Standard research methods, such as examining cells in the lining of vessel walls, are conducted by cell culture, meaning the cells are removed from their disease environment and placed in a culture dish. The culture conditions do not mimic the microenvironment of the cells when they are in their actual diseased state.

Studies that examine biopsy tissue from patients typically study extracts of the entire biopsy, which represents a mix of numerous tissue and cell types. Such whole-biopsy extract studies do not provide precise cell-specific information, Sen noted. The new approach identifies blood vessels in the human tissue in a matter of less than five minutes, followed by robot-assisted rapid dissection and collection of blood vessels from serial tissue sections. The collected tissue material can then be subjected to genome-wide screening.

Blood vessels are critical components of multiple diseases, so their quick identification and analysis at the cellular level has broad implications.

�The main strategies of limiting cancer are to stop the vascular supply that feeds the tumor. So if you know the biology of the blood vessel feeding the tumor, you can halt that action and the tumor can no longer grow,� Sen said. �In the case of chronic wounds, the tissue can grow only if blood vessels bring food and fuel � say, glucose and oxygen � to power the healing process. �In both diseases, you need a clear understanding of vascular biology.�

The tissue screened for the study of the genetics of wound healing is supplied by a new wound tissue bank at Ohio State, which holds more than 500 samples collected from seven U.S. centers affiliated with National Healing Corp. Ohio State�s Comprehensive Wound Center has a partnership with National Healing Corp., a private Florida company that manages 20 percent of the nation�s wound-healing centers

�Traditionally, in wound healing, there has been no way to tell what�s going on in the wound except by visualization and what a biopsy says � whether it�s infected or cancerous. We�re advancing the depth and level of this knowledge in our investigation,� said Dr. Gayle Gordillo, director of the plastic surgery research lab at Ohio State�s Medical Center and co-author of the paper.

Current studies are ongoing to test which genes predict healing and which genes are expressed in wounds that are chronic and predict a failure to heal. The researchers are taking biopsies from clinic patients with both healing and non-healing wounds and using the laser capture microdissection to study a homogeneous cell population and run the full genome screen.

The laser capture technology allows the scientists to zero in on the microvessels, which are expected to sprout when tissue is healing. If the microvessels in chronic wound samples are not sprouting, the researchers can then turn to endothelial cells � in the lining of blood vessel walls � to see if there is a genetic basis in those cells for why wounds do or don�t heal.

The first author of the study, Dr. Sashwati Roy, assistant professor of surgery, is a molecular biologist whose expertise lies in developing the method and sorting out the meaning of the data collected from the genes and identifying candidate genes involved in healing.

�One little genetic mutation can affect a person�s response to medications. The laser capture microdissection represents a powerful approach to conduct cell biology research utilizing patient biopsy material,� Roy said.

�The basic assumption has been that the blood vessels in intact skin and wounds are the same. What we�re seeing instead is that genes thought to be uniquely expressed in cancer are also expressed in wounds. None of these genes has been studied in wound healing,� Sen said. �So ultimately, this novel approach helps formulate new clinically relevant hypotheses. It�s a highlight for patient-based research.�

Focus on families aims to curb diabetes spread

Wed, 22 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Family lifestyles and their impact on the health of individual family members will be the focus of a new approach to preventing diabetes.

In the first study of its kind in Britain, researchers from the Universities of Edinburgh and Glasgow will test whether involving whole families in weight loss and fitness initiatives is effective in preventing the development of type 2 diabetes among high-risk family members.

The �1m study will focus specifically on people of Indian and Pakistani origin, who are five times more likely to develop late onset diabetes than the rest of the population.

Researchers will look particularly at families with at least one member who has a high risk of diabetes, possibly because they are overweight or do little exercise. The study, which is currently recruiting participants living in Edinburgh and Glasgow, will encourage all family members to adopt a healthy lifestyle with the aim that this motivates and supports those individuals at risk.

The study is funded by the National Prevention Research Initiative and aims to recruit 300 families. Dieticians will visit them at home over the next three years and provide culturally-specific advice on nutrition and exercise.

Researchers hope to reduce the incidence of type 2 diabetes by 50 per cent, and believe that by focusing on high-risk families, they will find strategies that can be applied more widely.

Raj Bhopal, Professor of Public Health at the University of Edinburgh and project leader, said: �Diabetes is increasing rapidly as we get more obese and less active. If we don�t take urgent action, it will spread in epidemic proportions.

�This family-based approach has never been tested before, but by involving the siblings and parents of at-risk individuals, we hope to provide a motivational and supportive strategy that could prevent diabetes not only in the UK, but on a global scale.�

Diabetes currently affects two million people in the UK, of which 90 per cent have type 2 (or late onset) diabetes that can lead to heart disease, stroke and blindness.

The condition develops when the body cannot make enough insulin, or when the insulin that is produced does not work properly (known as insulin resistance).

Jim McCaffery, Director of Acute Services and Workforce and executive lead for equality and diversity, NHS Lothian said: �We are delighted to be involved with this study. It is important that the health needs of all individuals are met and that we are sensitive to their needs.

�NHS Lothian is committed to meeting the equality and diversity needs of the local population by continually improving services and reducing health inequalities.�

Diabetes appears to increase risk of death for patients with acute coronary syndromes

Tue, 14 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) Individuals with diabetes and acute coronary syndromes (ACS) such as a heart attack or unstable angina have an increased risk of death at 30 days and one year after ACS, compared with ACS patients without diabetes, according to a study in the August 15 issue of JAMA.

The presence of elevated blood glucose levels, diabetes mellitus, or both contributes to more than 3 million cardiovascular deaths worldwide each year. With the increase in obesity, insulin resistance, and the metabolic syndrome, the worldwide prevalence of diabetes is expected to double by the year 2030, the authors write. They add that more than 1.5 million adults in the U.S. were newly diagnosed with diabetes in 2005, and nearly 65 percent of individuals with diabetes die from cardiovascular disease in the U.S., establishing it as the leading cause of death among this growing segment of the population. The effect of diabetes on the risk of death following ACS is uncertain.

Sean M. Donahoe, M.D., of Brigham and Womens Hospital and Harvard Medical School, Boston, and colleagues evaluated the independent effect of diabetes on risk of death following ACS at 30 days and 1 year using a large clinical trial database that included ACS. The study consisted of an analysis of patients with diabetes enrolled in randomized controlled trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62,036 patients (46,577 with ST-segment elevation myocardial infarction [STEMI; a certain pattern on an electrocardiogram following a heart attack] and 15,459 with unstable angina/nonSTEMI [UA/NSTEMI]), of whom 10,613 (17.1 percent) had diabetes.

The researchers found that the rate of death was significantly higher among patients with diabetes than among patients without diabetes at 30 days following either UA/NSTEMI (2.1 percent vs. 1.1 percent) or STEMI (8.5 percent vs. 5.4 percent). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with a nearly 80 percent increased risk of death at 30-days after UA/NSTEMI, and 40 percent increased risk of death at 30-days after STEMI.

At 1 year, diabetes remained a significant independent factor associated with all-cause death for patients presenting with UA/NSTEMI (65 percent increased risk of death) or STEMI (22 percent increased risk of death). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2 percent vs. 8.1 percent).

Despite modern therapies for ACS, diabetes conferred a significant independent excess mortality risk at 30 days and 1 year following ACS. Current strategies are insufficient to ameliorate the adverse impact of diabetes. Given the increasing burden of cardiovascular disease attributable to diabetes worldwide, our study highlights the need for a major research effort to identify aggressive new strategies to manage unstable ischemic heart disease among this high-risk population, the authors conclude.

UCLA researchers identify markers that may predict diabetes in still-healthy people

Tue, 14 Aug 2007 04:00:00 PST

( from http://www.rxpgnews.com ) In the first large scale, multiethnic study of its kind, researchers at UCLA have confirmed the role played by three particular molecules known as cytokines as a cause of Type 2 diabetes, and further, have identified these molecules as early biological markers that may be used to more accurately predict future incidences of diabetes among apparently healthy individuals.

Reporting in the August 15 issue of the journal Archives of Internal Medicine, Simin Liu, professor of epidemiology and medicine with a joint appointment in the School of Public Health and the David Geffen School of Medicine at UCLA, and colleagues have identified three inflammatory cytokines (cytokines are messenger molecules) tumor necrosis factor-alpha (TNF-á); interleukin-6 (IL-6); and high-sensitivity C-reactive protein (hs-CRP) that may be one of the causes of type 2 diabetes which afflicts roughly seven percent of the U.S. population.

Type 2 diabetes is the most common form of diabetes; about 90 to 95 percent of people who have diabetes have type 2. People with this condition produce insulin, but either their bodies dont make enough of it, or cant effectively use it.

Low-grade chronic inflammation of the body, which is reflected by elevated levels of inflammatory cytokines in the blood stream, may promote insulin resistance in the liver, muscles, and the vascular endothelium cells, the layer of thin, flat cells that lines the interior surface of blood vessels. Such inflammation can last for years before leading to type 2 diabetes, cardiovascular disease, or hypertension.

A blood test that looks for high levels of inflammatory cytokines could serve as an accurate predictor of diabetes in still-healthy people, years ahead of the traditional risk factors of obesity or insulin resistance. The finding also has implication for cancer research as well, said Liu, since people with diabetes are at greater risk of developing breast and colon cancers.

This is a final confirmation of earlier studies about the underlying biology behind type 2 diabetes, said Liu, who is also a member of the UCLA Jonsson Comprehensive Cancer Center. But those studies, he said, were either very small or animal studies. By comparison, he said, their study was more extensive in scale and involved human study volunteers. Our study identified 1,600 new cases of diabetes and measured the blood markers before they developed the disease.

The researchers took advantage of the Womens Health Initiative Observational Study (WHIOS), an ongoing, long term study that was designed to examine the association between behavior, socioeconomic status, diet, and other factors and the effect on a womans health. Liu and colleagues took baseline level measurements of inflammatory cytokines in apparently healthy women without any signs of diabetes who were between the ages of 50 and 79 years-old, then tracked their health for the next six years. The WHIOS study involved some 82,000 postmenopausal women who cut across multiple ethnicities, including whites, blacks, Hispanics, and Asian/Pacific Islanders. At the time of follow-up, Liu and colleagues compared 1,584 women, now diagnosed with type 2 diabetes, and matched them by age, ethnicity and other factors to 2,198 other women in the study who remained free of the disease.

While all three cytokines were found to be significantly related to an increased risk of clinical diabetes, hs-CRP appeared to be a more consistent predictor of increased risk in all four ethnic groups. These associations were independent of traditional risk factors such as obesity or elevated levels of glucose and insulin, previously reported by Liu and colleagues in the same multiethnic sample.

The pro-inflammatory state is often linked to obesity, said Liu, which can lead to insulin resistance. So, identifying these markers by a simple blood test well before a disease begins not only can help improve mechanistic understanding of the disease, but also offer alternatives to lifestylehitting an optimal balance of nutrition, for example, and engaging in more exercise - relatively simple things that can prevent disease.