Scientists Successfully Test New Anti-Obesity Vaccine

LA JOLLA, CA, July 31, 2006 - In what may be the first published breakthrough of its kind in the global battle against obesity, scientists at The Scripps Research Institute have developed an anti-obesity vaccine that significantly slowed weight gain and reduced body fat in animal models.

The study is being published in an advanced, online edition of the Proceedings of the National Academy of Sciences during the week of July 31 to August 4.

In the new study, mature male rats immunized with specific types of the active vaccine ate normally yet gained less weight and had less body fat, indicating that the vaccine directly affects the body's metabolism and energy use. This finding may be especially important to stop what is commonly known as "yo-yo dieting," the cycle of repeated loss and regain of weight experienced by many dieters. The new vaccine, which is directed against the hormone ghrelin (pronounced "grell-in"), a naturally occurring hormone that helps regulate energy balance in the body, has shown the potential, in animal models at least, to put an end to that risky and often futile struggle.

These findings may mark a turning point in the treatment of obesity by confirming the effectiveness of immunopharmacotherapy to combat this serious and growing global problem. Immunopharmacotherapy engages the immune system, specifically antibodies, to bind to selected targets, directing the body's own immune response against them. This approach is being tested in a number of other areas including drug addiction, especially addiction to cocaine and nicotine.

"The study shows our vaccine slows weight gain and decreases stored fat in rats," said a senior author of the paper Kim Janda, Ph.D., who is Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research, a member of The Skaggs Institute for Chemical Biology, and director of the Worm Institute of Research and Medicine. "While food intake was unchanged in all testing groups, those who were given the most effective vaccines gained the least amount of weight. To have an impact on appetite and weight gain, ghrelin first has to move from the bloodstream into the brain - where, over long periods, it stimulates the retention of a level of stored energy as fat. Our study is the first published evidence proving that preventing ghrelin from reaching the central nervous system can produce a desired reduction in weight gain."

Ghrelin, a gastric endocrine hormone produced primarily in the stomach, plays a physiological role in energy homeostasis, although the full extent of that role remains unknown. It was first identified in 1999 as a naturally occurring ligand - a molecule that binds to another to form a larger molecular complex - for a growth hormone secretagogue receptor. What is known is that ghrelin promotes weight gain and fat storage through its metabolic actions, decreasing the breakdown of stored fat for energy as well as curbing energy expenditure itself. During periods of weight loss, such as dieting, the body produces high levels of ghrelin to slow down fat metabolism, encourage eating, and promote fat retention, changes which normally make it difficult to lose weight and keep it off.

"We're not claiming that our study answers the question of obesity treatment once and for all," Janda said. "What we are saying - and what our study confirms - is that this looks like a serious workable solution to the problem. And while much more research is needed to understand the full therapeutic potential of immunopharmacotherapy in combating obesity, these initial results are extremely positive. Right now it appears that active vaccination against ghrelin is one avenue that can slow weight gain and fat build-up in the body."

Producing an Active Vaccine

"Through our work in the development of immunopharmacotherapy-based vaccines against drug addiction, we became interested in the problem of obesity," Janda said. "While there were numerous possible hormones involved in obesity that could be targeted, we decided that ghrelin would be a good starting point to examine such a hypothesis."

The researchers developed three active vaccines (labeled Ghr1-2-3) to immunize adult male rats. Those animals immunized with Ghr1 or Ghr3 showed greater and more selective plasma-binding capacity for the active form of ghrelin - keeping the hormone in the blood and away from the brain and the central nervous systemóas compared to Ghr2 or control models.

During the study, the rats immunized with Ghr1 and Ghr3 ate normally but, once antibody levels increased, accrued less body weight and fat, indicating an increase in the body's use of energy, a finding supported by studies of genetically altered mice. For example, the authors of the study write, "mice deficient for ghrelin or its receptor store less of their consumed food and resist accumulating body weight and fat on energy dense diets. [Ghrelin-deficient mice] also expend more energy and [are more active], [while] ghrelin receptor deficient mice show increased [utilization of fat as a key energy source]."

The study did note, however, that the immunized rats were fed low-energy, low-fat, and relatively less palatable chow diets and were comparatively lean. "Whether active immunization against ghrelin would help prevent the development of obesity caused by... high-fat "Western" diets or would facilitate weight loss once obesity is established" remains uncertain, the study added.

Eric Zorrilla, Ph.D., a Scripps Research assistant professor, member of the Harold L. Dorris Neurological Research Institute, and a lead author of the study, said, "The rats who received the most effective vaccines didn't eat differently than the others, including the control models. That makes our findings exciting therapeutically - the vaccine slows the rate of weight gain, while still allowing for normal eating habits. A vaccine against ghrelin also is particularly compelling in terms of the well-documented problems of human dieting. When you diet, the body responds as if it was starving and produces ghrelin to slow down fat metabolism and stimulate eating, changes meant to help retain and regain body fat. As a result, many people end up regaining the weight they lost and more once they go off their diets. This vaccine may have the real potential to prevent or seriously reduce yo-yo dieting, the repetitive cycle of weight loss and gain, because it interferes with ghrelinís ability to promote weight gain and fat accumulation."

There is broad speculation that ghrelin evolved as a response to the feast or famine conditions of early humans. Those who were genetically predisposed to eat heartily and store fat efficiently during periods of plenty were more likely to survive the next round of scarcity and passed this trait onto the next generation. In recent years, however, that powerful genetic legacy has come in direct conflict with the dangerous phenomenon of overeating in the developed world.

The Worldwide Threat of Obesity

Obesity remains a serious and growing problem for millions of people worldwide and is a contributing risk factor for a number of other diseases including heart disease, various cancers, Type 2 diabetes, stroke, arthritis, and depression. Although a number of pharmaceutical approaches have been taken to try to help people better control their body weight, few if any have been successful and several, including the drugs fenfluamine (a component of "Fen-Phen") and ephedrine, have been pulled from the market by the U.S. Food and Drug Administration.

According to recent reports from the World Health Organization, about 1 billion people worldwide are overweight or obese, most of them in the developed world. In the United States, for example, the National Health and Nutrition Examination Survey found that, in 2003 to 2004, approximately 66 percent of all American adults 20 years of age or older were overweight or obese. Almost four out of every five American men aged 40 to 59 were classified as overweight, according to a 2006 study published by the Journal of the American Medical Association. Even Japan, long a dietary exception, has experienced a rise in obesity and diabetes as Western-style eating habits continue to take hold in that country.

"The reason we looked at immunopharmacotherapy vaccines to treat obesity," Janda said, "was because drugs seeking to modulate obesity-driven receptors via agonist or antagonist effects have been remarkably unsuccessful. They are effective only while treatment is maintained and when treatment stops, weight returns. For obesity treatments to work, they must affect energy intake, absorption, expenditure, or storage. Our new vaccine works by changing expenditure or storage."

The ghrelin vaccine produced by Scripps Research scientists is not the only one being tested. Cytos, a Swiss-based biotechnology company, is currently testing a ghrelin-based vaccine in a combined phase I/II study with 112 obese patients. Like the Scripps Research vaccine, the Cytos vaccine produces antibodies that inhibit the uptake of ghrelin by the brain. However, Janda and Zorrilla noted, there are significant differences between the two vaccines.

"Compared to other ghrelin-based vaccines being studied," Zorrilla said, "our vaccine was designed to raise antibodies against the active form of ghrelin, which, we believe, makes it distinctive. "In addition," Janda stated, "the most effective forms of the vaccine contained an unnatural ester functionality - this not only increases water solubility, but minimizes aggregation and micelle formation, which provides an additional, little-known therapeutic window for the success of a productive immune response. Simply stated, this translates into a better obesity vaccine."

In addition, Janda said, the Scripps Research vaccine did not produce a systemic inflammatory response. General inflammatory responses can occur with fevers or even cancers, causing lack of food intake and weight loss. That was not the case with the new vaccine.

Other authors of the study, titled "Vaccination against weight gain," include Shinichi Iwasaki, Jason A. Moss, Jason Chang, Jonathan Otsuji, and Michael M. Meijler of The Scripps Research Institute and its Skaggs Institute for Chemical Biology, as well as Koki Inoue of Osaka City University.

The study was supported by the National Institute of Diabetes, Digestive, and Kidney Disorders and The Skaggs Institute for Chemical Biology.

Posted by dlife at 10:56 AM | Comments (0)

Exercise in Itself Improves Blood Glucose Control in Type 2 Diabetes

July 21, 2006 (Newswise) — Exercise, dietary changes and medication have long been the cornerstones of managing type 2 diabetes. But few studies examine how exercise actually benefits these patients.

Now, a new systematic review shows that exercise helps regulate blood glucose (sugar) levels, increases the body’s sensitivity to insulin, and decreases blood lipids (fats) while also helping to burn body fat.

“Type 2 diabetes is an increasing problem in Western societies and is associated with increased rates of overweight and obesity,” said review co-author Elizabeth Elliott, M.D., of the University of Sydney and Children’s Hospital at Westmead, in Australia. “In this study, we wanted to determine if there was an independent effect of exercise — separate from dietary modification and medications — in improving outcomes in patients with type 2 diabetes.”

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

The study, which reviewed data from 14 randomized controlled trials, included a total of 377 participants. The average age range in studies was 45 to 65 years with slightly more men than women. All participants had type 2 diabetes and the only difference between groups was that they were assigned to either no exercise or to a prescribed exercise regime.

The types of exercise programs in each study varied widely. Resistance training and aerobic workouts were the most common, although one study involved qi gong.

Exercise sessions varied from one to seven times a week, with most studies involving three sessions a week. Sessions lasted from 30 minutes to two hours, with half the studies using hour-long sessions. The studies were short term, ranging from eight weeks to 12 months with most lasting less than six months.

“We were interested in whether a prescribed exercise regime versus no exercise regime would actually improve blood sugar control, and it did,” said Elliott. The researchers determined this by looking at the percent of glycated hemoglobin in the blood, also known as an A1C test. The American Diabetes Association considers A1C values to be the best indicator of long-term blood glucose control.

Participants who exercised had an overall decrease of 0.6 percent of A1C levels. While that may not sound like much, it represents a 30 percent improvement towards the goal of attaining an A1C of 7 percent, and a 20 percent improvement towards a normal A1C of 6 percent.

“This was a both a statistically and clinically significant drop,” said Elliott. “It’s comparable to the drop that clinicians would like to see if prescribing medication” to regulate blood sugar, she said.

“Many people with type 2 diabetes find when they start walking daily, for example, that blood sugar control becomes much easier. That’s been known anecdotally for a long time,” Elliott said. “Our study gives justification to the recommendation that exercise is important.”

Participants enrolled in an exercise program also lost significantly more fat around the abdominal organs and under the skin, compared to those who didn’t exercise.

Exercising participants didn’t actually lose any weight, however — probably because exercise helps replace fat with heavier muscle tissue, researchers said, and because the average length of the studies was too short to show weight loss. Muscle tissue helps in the metabolism of insulin and blood sugar regulation.

Participants who exercised also experienced a significant lowering of blood triglycerides, which are often elevated in patients with diabetes. Excess triglycerides have been linked to coronary artery disease.

“Our review shows that diabetes management can be enhanced by nonmedical measures such as exercise,” Elliot says. “All patients with diabetes would probably benefit from a consultation not only with a dietitian but also a physiotherapist, exercise physiologist or sports medicine physician who can create for them a sustainable exercise program.”

Neal Kohatsu, M.D., president of the American College of Preventive Medicine, concurs. “There is a strong body of evidence that exercise in partnership with other healthy lifestyle and medical interventions does have benefit” for patients with type 2 diabetes, he said. “People often think that you have to be a triathlon competitor to get benefits from exercise. In fact there is substantial benefit going from couch potato to being even modestly active.”

While there were no documented adverse effects from any of the exercise regimes in studied, Kohatsu says that patients with type 2 diabetes should consult with their physician before starting or changing an exercise program. “There are issues related to diabetes and exercise that one has to be cautious about. For example, good foot care is important because of potential problems with circulation and neuropathy,” he said.

In addition, he said that insulin-dependent diabetic patients may be at risk for hypoglycemia, or low blood sugar, when exercising and need to know how to monitor and treat themselves if they should become hypoglycemic.

Age, cardiovascular status, and other factors may also influence what kind of exercise is best for an individual patient with type 2 diabetes.

Posted by dlife at 12:40 PM | Comments (0)

Diabetes Drug May Also Treat Alzheimer's Disease

CHARLOTTESVILLE, Va., July 17, 2006 – Treatment of high blood sugar may have a scientific connection to memory loss that could, one day, benefit millions of people with Alzheimer’s Disease, which affects up to 4.5 million older Americans, bringing with it impaired thinking and memory.

New research at the University of Virginia Health System and Case Western Reserve University shows that a drug approved by the Food and Drug Administration to treat type 2 diabetes may hold promise in treating Alzheimer’s as well, without serious side effects. “We believe that the drug may reduce the body’s inflammatory reaction to one of the toxic components that builds up in Alzheimer’s, called amyloid plaque,” said Dr. David Geldmacher, an associate professor of neurology at UVa.

The drug, called pioglitazone, was tested in a placebo-controlled trial involving 25 people with mild to moderate Alzheimer’s. The study assessed the safety of the drug and, although the treatment appeared to reduce Alzheimer’s progression, the study was too small for investigators to be sure of the effects on memory and everyday abilities. However, the findings are promising enough, researchers say, to carry out larger studies of pioglitazone.

The research was presented July 16 to the world’s largest Alzheimer’s conference, ICAD 2006, in Madrid, Spain. It was selected by ICAD organizers to be highlighted because of a growing sense of the relationship between diabetes and Alzheimer’s.

"We don’t know exactly how pioglitazone works in Alzheimer’s, but there are two possibilities,” Geldmacher said. “It could be that the drug reduces the body’s response to the amyloid protein found in Alzheimer’s. Or, it could be that this drug helps brain cells function. The real advantage is that it’s a completely novel approach to treating the disease.”

In the next few years, Geldmacher and his colleagues hope to study the effectiveness of pioglitazone in a group of 200 to 300 Alzheimer’s patients nationwide. “If it works, this treatment might allow people to better hold on to memory and brain function over a period of time, despite having Alzheimer’s,” Geldmacher said. “It could also complement other treatments and become part of a multi-pronged approach to Alzheimer’s treatment.” Right now, there are 5 drugs approved by the FDA to treat Alzheimer’s, Geldmacher said, but pioglitazone is unrelated to any of the others. The trial of pioglitazone at UVa and Case Western Reserve was supported by the National Institutes of Health and Takeda Pharmaceuticals North America, Inc., which manufactures the drug.

Posted by dlife at 12:51 PM | Comments (0)

Disetronic Medical Systems Inc Announces a Voluntary Nationwide Recall of Disetronic D-TRONplus Power Packs used in D-TRONplus Insulin Pumps

Fishers, Indiana, July 13, 2006 (FDA) - Disetronic Medical Systems Inc. (Disetronic) of Fishers, IN announced today a voluntary nationwide recall of the Disetronic D-TRONplus Power Packs, that power the D-TRONplus Insulin Pump. There is the real potential that the power pack could shut down the D-TRONplus Insulin Pump without any warning. If a shut down occurs, insulin delivery is interrupted. An interruption in insulin delivery may lead to uncontrolled diabetes mellitus, resulting in hyperglycemia, which may lead to serious patient injury and/or death. This is an Urgent Device Correction notification to health care professionals and their patients not requiring product removal at this time.

The abrupt shutdown of the D-TRONplus insulin pump is due to a change in the battery design by its manufacturer. As a result, the pump does not have enough time to recognize a decrease in the power supply, which causes the pump to shut down before the audible and vibrating low power alarms are triggered.

Until further notice all pump users must put a new power pack into their insulin pump every two weeks to prevent their pump from turning off without any warning. It is important this two week period not be extended. Disetronic and their distributors will supply power packs free of charge by UPS next day shipment to all D-TRONplus users until corrective actions have been implemented. Every user will receive a power pack together with detailed instructions.

Disetronic and their distributors will also provide every user with a new power pack every two weeks. Distribution of these power packs will begin on Thursday, July 13, 2006.

This is a temporary fix to the power pack problem until adequate supplies of the corrected battery can be obtained. We will update all users when the problem is resolved. Disetronic has tested the replacement design being shipped and we have data to verify a two week use period in the pumps without failure.

If you are a physician or a patient who has experienced a problem with any Disetronic D-TRONplus Power Packs, please notify Disetronic at 1-800-688-4578.

An interruption in insulin delivery may lead to uncontrolled diabetes mellitus, resulting in hyperglycemia, which can lead to serious patient injury and/or death. The symptoms of hyperglycemia may include nausea/vomiting, blurred vision, excessive thirst or hunger, frequent urination, fatigue/tiredness/sleepiness, headache, fruity acetone breath, abdominal pain, and coma. Patients experiencing these symptoms are advised to check their blood glucose level to ensure that they are within acceptable ranges as defined by their healthcare team. Patients are advised to contact their health care provider if they have questions. Users of the D-TRONplus pumps should monitor pumps closely to ensure adequate delivery of insulin. Clinicians should exercise maximum vigilance in monitoring patients, in the event of any of the aforementioned signs or symptoms.

Disetronic D-TRONplus Power Packs are available by prescription only for diabetes patients who use insulin pump therapy. Disetronic is notifying by direct mail affected customers, healthcare providers and its distributors of this action.

This recall is being conducted with the knowledge of the U. S. Food and Drug Administration.

Any adverse reactions or adverse events experienced with the use of this product, and/or quality problems should also be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088, by Fax at 1-800-FDA-0178, by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.

Posted by dlife at 12:54 PM | Comments (0)

Short Legs Linked to Diabetes?

Low Leg-to-Height Ratio May Indicate Diabetes Risk, Study Shows

July 12, 2006 (WebMD) - Type 2 diabetes, the most frequent kind, may be slightly more common among adults with disproportionately short legs than in their leggier peers.

So says a study in the July edition of Diabetes Care.

The researchers, who included Keiko Asao, M.D., MPH, of Johns Hopkins University in Baltimore, aren’t quite sure how to explain their findings. Hormones or nutrition before birth or in childhood may affect both development and diabetes risk, they suggest.

Type 2 diabetes is often linked to excess weight.

Leg Link To Diabetes?

In their study, Asao and colleagues checked data from a U.S. health survey given from 1988-1994. Participants included about 3,600 men and 3,800 women aged 40 to 74 years (average age: about 55 years).

The nationally representative survey included physical exams and lab tests. During those checkups, participants' height and leg length were measured.

Being short didn’t affect diabetes risk, after adjusting for other factors. But having a low leg-to-height ratio was associated with a slightly higher risk of type 2 diabetes, based on blood sugar tests given during the checkups, even after weighing other risk factors.

More Established Risk Factors

While the researchers try to figure out the leg length connection, there are plenty of other, more established diabetes risk factors to watch for, including:

Family history of diabetes
Age 45 and older
Being overweight
Sedentary lifestyle
High blood pressure
Abnormal cholesterol levels
History of diabetes during pregnancy
History of polycystic ovary syndrome (PCOS)
History of vascular disease, such as stroke
Race or ethnic background (diabetes risk is higher for Hispanics,
blacks, Native Americans, and Asians).
Diabetes Signs

Diabetes often goes undiagnosed. More than 6 million Americans have type 2 diabetes and don’t know it, according to the National Diabetes Information Clearinghouse.

Warning signs include:

Increased thirst
Increased hunger
Fatigue
Increased urination, especially at night
Weight loss
Blurred vision
Sores that do not heal
See your doctor to get screened for diabetes.

Posted by dlife at 12:31 PM | Comments (0)

GlaxoSmithKline Announces FDA Approval and the Launch of Avandamet(R) (Rosiglitazone Maleate and Metformin HCl) as Initial Therapy in the Treatment of Type 2 Diabetes

Avandamet Combines Two Oral Agents - Rosiglitazone, the Most Widely Used Insulin Sensitizer, with a Leading Diabetes Therapy, Metformin - To Help Patients Improve Blood Sugar Control

PHILADELPHIA, July 11 /PRNewswire/ -- GlaxoSmithKline announced today FDA approval of Avandamet(R) (rosiglitazone maleate and metformin HCl) for use as initial treatment of type 2 diabetes as an adjunct to diet and exercise. Avandamet was previously approved as a second-line therapy -- it was indicated for use in patients who were uncontrolled on metformin monotherapy. Now, with this recent approval, physicians can start their type 2 diabetes patients on Avandamet.

Avandamet is the only combination of a thiazolidinedione, rosiglitazone maleate (separately marketed as Avandia(R)) and metformin HCl, with approved use as initial therapy of type 2 diabetes. Avandamet is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus when treatment with dual rosiglitazone and metformin therapy is appropriate.

The announcement of the FDA approval for Avandamet for use as initial therapy in type 2 diabetes coincides with GlaxoSmithKline's announcement that its supply of Avandamet has been re-established.

"Many people with type 2 diabetes need to take more than one medication to treat the disease in different ways. The combination of rosiglitazone and metformin provides two complementary mechanisms of action," said Barry Goldstein, M.D., Ph.D., director, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University, Philadelphia. "Rosiglitazone targets insulin resistance, an underlying cause of type 2 diabetes, whereas metformin primarily works to reduce the amount of blood sugar (or glucose) produced by the liver. In fact, a clinical trial comparing Avandamet to both rosiglitazone alone and metformin alone showed that patients taking Avandamet achieved significantly lower blood sugar levels than with either monotherapy alone."

Nearly 18 million Americans have type 2 diabetes, the most common form of diabetes. Type 2 diabetes is characterized by high blood sugar levels that occur when the body does not produce enough insulin or does not respond properly to its own natural insulin, a condition called insulin resistance. To manage diabetes, it is important for patients to achieve the blood sugar goal set by their physicians. Blood sugar control is measured by the HbA1C test, or A1C, which reflects a person's average blood sugar levels over the previous two to three months. The American Association of Clinical Endocrinologists recommends an A1C of 6.5% or lower. The American Diabetes Association recommends an A1C of less than 7%. Lowering blood sugar levels can help reduce the risk of diabetes-related complications,
such as heart disease, stroke, blindness, loss of limbs and kidney disease.

"GlaxoSmithKline is committed to developing diabetes therapies to treat a disease that has reached epidemic proportions in the United States and throughout the world," said Anne M. Phillips, MD, vice president of Clinical for North America Cardiovascular-Metabolic, GlaxoSmithKline. "With the approval of Avandamet for use as initial therapy as an adjunct to diet and exercise, GSK offers this effective and convenient option now for initial treatment of type 2 diabetes. This combination of rosiglitazone and metformin can help patients get their blood sugar under control."

Importance of Aggressive Diabetes Management

Diabetes experts are setting more stringent standards that reflect the importance of maintaining tight blood sugar control. "Combination therapy with medications that work in different ways is often needed to help patients reach and maintain blood sugar goals," said Dr. Goldstein. "An advantage of Avandamet is that it combines two medications with complementary mechanisms of action in one convenient tablet."

Avandamet: Initial Therapy in Diabetes Management

Avandamet was originally approved in the U.S. in 2002, and is available in four tablet strengths of rosiglitazone/metformin, respectively: 2 mg/500 mg, 4 mg/500 mg, 2mg/1000mg, and 4mg/1000mg. Avandamet, as a two-in-one therapy, is the most economical thiazolidinedione (TZD)-metformin combination on the market.

Important Safety Information for Avandamet

Avandamet, along with diet and exercise, helps improve blood sugar control. It is a combination of two drugs - rosiglitazone maleate and metformin HCl.

A small number of people who have taken metformin, one of the components of Avandamet, have developed a rare yet serious condition called lactic acidosis (a buildup of lactic acid in the blood). Lactic acidosis occurs most often in people with kidney problems and can be fatal in up to one half of the cases. You should not take Avandamet if you have kidney problems. Tests should be used to check your kidneys before and while taking Avandamet. You should not drink alcohol excessively when taking Avandamet. If you are taking medicines for heart failure, you may be at increased risk of lactic acidosis.

Tell your doctor if you have heart problems or heart failure. Avandamet can cause your body to keep extra fluid which leads to swelling and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. If you have swelling or fluid retention, shortness of breath or trouble breathing, an unusually rapid increase in weight, or unusual tiredness while taking Avandamet, call your doctor right away.

You should not take Avandamet if you have liver problems. Blood tests should be used to check for liver problems before starting and while taking Avandamet. Tell your doctor if you have liver disease, or if you experience unexplained tiredness, stomach problems, dark urine or yellowing of skin while taking Avandamet.

Tell your doctor about all of the medicines you are taking.

Avandamet may increase your risk of pregnancy. Talk to your doctor before taking Avandamet if you could become pregnant or if you are pregnant.

If you are nursing, you should not take Avandamet.

Your doctor should check your eyes regularly. Very rarely, some people have experienced vision changes due to swelling in the back of the eye while taking rosiglitazone, a component of Avandamet.

About GlaxoSmithKline

GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Posted by dlife at 12:58 PM | Comments (0)

New Data Demonstrate Benefits of Initial Use of Avandaryl(R) (Rosiglitazone Maleate and Glimepiride) in People With Type 2 Diabetes

Glycemic Control and Improvements in Insulin Resistance Seen in People Taking Avandaryl

WASHINGTON, June 10, 2006 (PRNewswire) New research presented today at the 66th Annual Scientific Sessions of the American Diabetes Association (ADA) show the benefits of the initial use of Avandaryl in helping people with type 2 diabetes achieve blood sugar targets and improving insulin sensitivity. These data suggest that treatment of drug-naive people with Avandaryl may be more efficacious than using one therapy alone. Avandaryl is the only therapy available that combines a thiazolidinedione (TZD), rosiglitazone maleate -- separately marketed as Avandia(R) -- with a sulfonylurea, glimepiride -- separately marketed as Amaryl(R) -- to treat type 2 diabetes.

"Given the progressive nature of type 2 diabetes, most patients will eventually need more than one therapy to effectively control blood sugar levels over time and reduce their risk of potentially serious diabetes-related complications, such as heart disease and stroke," said Barry Goldstein, M.D., Ph.D., director, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University, Philadelphia, and an author of one of the papers. "Using more effective treatment approaches earlier in the course of the disease, including the use of combination medications, is important for the management of type 2 diabetes."

In this study (presented as abstract: 541-P), "Rosiglitazone (RSG) and Glimepiride (GLIM) Fixed-Dose Combination (FDC) Provides Superior Glycemic Control Compared with GLIM and RSG Monotherapies in Drug-Naove Individuals with Type 2 Diabetes (T2DM)," examined glycemic control as measured by A1C and fasting plasma glucose (FPG). In this study, people taking Avandaryl had a rapid reduction in FPG levels, seen as early as after 2 weeks.

Also, superior reductions in A1C levels were seen with Avandaryl compared to rosiglitazone or glimepiride, with significantly more patients reaching the A1C goals recommended by the ADA and the American Association of Clinical Endocrinologists (AACE). The ADA recommends an A1C of less than 7%, and AACE recommends an A1C of 6.5% or less. Of patients taking Avandaryl, up to 75% reached ADA's target A1C vs. 49% of patients taking glimepiride and 46% of patients taking rosiglitazone. Similarly, up to 56% of patients taking Avandaryl reached AACE's target A1C vs. 32% of patients taking glimepiride and 30% of patients taking rosiglitazone.

Among patients in the two Avandaryl treatment arms, the mean reductions from baseline in A1C levels were 2.4% to 2.5% vs. a mean reduction from baseline in A1C of 1.8% among patients taking rosiglitazone monotherapy and 1.7% among patients taking glimepiride monotherapy. At baseline, the patients studied had an A1C of 9% to 9.2%.

Other findings from this study (abstract 475-P), "Initial Treatment with Rosiglitazone (RSG) and Glimepiride (GLIM) Fixed-Dose Combination (FDC) Reduces Cardiovascular Risk Markers and Improves Insulin Sensitivity in Patients with Type 2 Diabetes (T2DM)," Avandaryl demonstrated effects in addition to glycemic control, including increases in estimates of beta-cell function and improvements in C-reactive protein and PAI-1, which are two cardiovascular inflammatory markers. Further, a reduction in insulin resistance was seen in patients taking Avandaryl or rosiglitazone, but not in those taking glimepiride monotherapy.

Avandaryl was generally well tolerated, with an adverse event profile similar to its component therapies. There was a similar incidence of confirmed hypoglycemic events with Avandaryl as compared to glimepiride. There was a low incidence of edema and anemia with Avandaryl. There was a small average weight gain with rosiglitazone and glimepiride, with more weight gain seen with Avandaryl.

The study is a 28-week, multi-center trial with 901 patients randomized to one of four treatment arms: glimepiride (1mg titrated up to 4mg OD), rosiglitazone (4mg up to 8mg), or one of the two rosiglitazone/glimepiride fixed-dose combination arms, (4mg/1mg up to 4mg/4mg in FDC A and 4mg/1mg up to 8mg/4mg in FDC B); 883 patients constituted the efficacy population.

"Avandaryl -- and other combination medications that include rosiglitazone -- are effective in managing type 2 diabetes," said Hubert Chou, M.D., Ph.D., senior director, CV Metabolism Medicine Development Center, GlaxoSmithKline. "Physicians need different therapies to adequately control their patients' blood sugar levels. GlaxoSmithKline is committed to providing convenient and effective treatment options to help the growing number of people with type 2 diabetes to manage their disease."

More than 18 million Americans have type 2 diabetes, the most common form of diabetes. Type 2 diabetes is characterized by high blood sugar levels that occur when the body does not produce enough insulin or does not respond properly to its own natural insulin, a condition called insulin resistance. Normally, insulin is released into the bloodstream from the beta-cells of the pancreas, however, when a person is insulin resistant, the pancreas produces more insulin in order to keep blood glucose levels under control. Eventually, the pancreatic beta-cells become exhausted and can no longer function properly. As type 2 diabetes progresses, the combined effects of insulin resistance and beta-cell dysfunction can make it increasingly difficult for a patient to control glucose levels. When sugar builds up in the blood instead of going into the cells, it can starve the cells of energy and over time, high blood sugar levels can cause diabetes-related complications, affecting the eyes, kidneys, nerves or heart.

Important Safety Information for Avandaryl

Avandaryl, along with diet and exercise, helps improve blood sugar control. Avandaryl is a combination of two drugs -- rosiglitazine maleate and glimepiride.

Avandaryl may cause low blood sugar. Lightheadedness, dizziness, shakiness or hunger may mean that a patients' blood sugar is too low. If patients have kidney problems, they may need a lower dose of Avandaryl to reduce problems with low blood sugar. Patients should talk to their doctor if low blood sugar is a problem for them.

Patients should tell their doctor if they have heart problems or heart failure. Avandaryl can cause the body to keep extra fluid which leads to swelling and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. If patients have swelling or fluid retention, shortness of breath or trouble breathing, an unusually rapid increase in weight, or unusual tiredness while taking Avandaryl, they should call their doctor right away.

Patients should not take Avandaryl if they have liver problems. Blood tests should be used to check for liver problems before starting and while taking Avandaryl. Patients should tell their doctor if they have liver disease, or if they experience unexplained tiredness, stomach problems, dark urine or yellowing skin while taking Avandaryl.

Patients should tell their doctor about all of the medicines they are taking.

Avandaryl may increase the risk of pregnancy. Patients should talk to their doctor before taking Avandaryl if they could become pregnant or if they are pregnant. If patients are nursing, they should not take Avandaryl.

Doctors should check their patients' eyes regularly. Very rarely, some patients have experienced vision changes due to swelling in the back of the eye while taking rosiglitazone, a component of Avandaryl.

Posted by dlife at 02:03 PM | Comments (0)

Type 2 Diabetes Increases the Risk of Glaucoma in Women

July 10, 2006 (Newswise) — A 20-year study of women in the Nurses’ Health Study has shown that Type 2 diabetes is associated with primary open angle glaucoma (POAG), the most common form of glaucoma, accounting for about 60 to 70% of all glaucomas. The study is published in the July issue of the journal Ophthalmology.

Researchers at the Massachusetts Eye and Ear Infirmary, Brigham and Women’s
Hospital, Harvard School of Public Health and Harvard Medical School observed 76,3128 women who were enrolled in the Nurses’ Health Study from 1980 to 2000. Eligible participants were at least 40 years old, did not have POAG at the beginning of the study, and reported receiving eye exams during follow-up. After controlling for age, race, hypertension, body mass index, physical activity, alcohol intake, smoking and family history of glaucoma, they found that type 2 diabetes was positively associated with POAG. However, the relation between type 2 diabetes and POAG did not increase with longer durations of type 2 diabetes.

“The study supports the notion that type 2 diabetes is associated with an increased risk of glaucoma,” said Louis Pasquale, M.D., lead author of the study and co-director of the Glaucoma Service at the Massachusetts Eye and Ear Infirmary (MEEI) and an Assistant Professor of Ophthalmology at Harvard Medical School. “While obesity fuels the type 2 diabetes epidemic, it appears that factors unrelated to obesity contribute to the positive association between type 2 diabetes and glaucoma. We were surprised to find this. Our study had a large enough sample to allow us to focus on type 2 diabetes only and to study its relation to newly diagnosed POAG cases. We were also able to correct for other factors that could contribute to glaucoma. Our work suggests, but in now way proves, that factors other than lifestyle behavior contributing to insulin resistance could lead to elevated
intraocular pressure and glaucoma.”

According to the National Eye Institute, POAG affects more than 2 million individuals in the United States and is one of the leading causes of blindness. With the rapid aging of the U.S. population, the number of individuals affected by the disease will increase to more than 3 million by 2020.

Posted by dlife at 01:03 PM | Comments (0)

ACTOS® (pioglitazone HCl) To Be Studied In New Trial Investigating Its Effects On Atherosclerosis In Patients With Type 2 Diabetes

Study further examines possible cardiovascular effects of ACTOS beyond glycemic control

Washington, DC, June 9, 2006 – Researchers today at the American Diabetes Association (ADA) 66th Annual Scientific Sessions presented data showing the relationship between baseline characteristics and cardiac risk factors in patients enrolled in a new clinical trial called CHICAGO (Carotid intima-media tHICkness in Atherosclerosis using pioGlitazOne). This is the largest and longest study to examine the effects of ACTOS on measures of the atherosclerotic disease process in patients with type 2 diabetes, most of whom had no clinical evidence of heart disease.

“While earlier and smaller studies found that ACTOS reduced carotid intima-media thickness, given the size and duration of the CHICAGO trial, we hope to gather further information about the effect of ACTOS on blood vessel health and atherosclerosis,” said Theodore Mazzone, M.D., F.A.C.P., professor of medicine and director of the Section of Endocrinology, Diabetes and Metabolism at the University of Illinois at Chicago. “We look forward to further study findings, as we hope they can provide important information and insight about management of cardiovascular disease in people with type 2 diabetes.”

The CHICAGO trial is an 18-month, multicenter, randomized study that has enrolled 439 patients with type 2 diabetes, all from the Chicago area, thus the name of the study. The primary goal was to compare the effects of ACTOS versus glimepiride, a sulfonylurea, on carotid intima-media thickness (CIMT), defined as the thickness of the inner lining of a patient’s neck arteries. It is also assessing the occurrence of cardiovascular events (i.e., death, heart attack and stroke) and cardiovascular disease risk factors among patients with type 2 diabetes.

CIMT is a preferred, noninvasive measure of atherosclerosis, which can lead to heart attack or stroke because of reduced or blocked blood flow through the arteries. CHICAGO will also examine another marker of atherosclerosis, coronary artery calcium (CAC): calcium build-up in the arteries of the heart in the same population. Heart disease and stroke account for 65% of deaths in patients with diabetes.

CHICAGO Data: Relationship Between Baseline Characteristics And Coronary Artery Calcium

A multivariable analysis, a tool for determining the relative contributions of different causes to a significant event, of over 30 traditional and emerging cardiac risk factors (including apolipoproteins, inflammatory and coagulation markers and visceral and total abdominal fat) confirmed that age, systolic blood pressure, gender, race/ethnicity, and triglyceride levels were significant predictors of CAC.

“There is a growing body of science suggesting that ACTOS may have benefits beyond glycemic control,” said Robert Spanheimer, M.D., medical director for diabetes and metabolism at Takeda Pharmaceuticals North America, Inc. “CHICAGO will be viewed in the context of other large cardiovascular studies with ACTOS: the PROactive study, which found that ACTOS may reduce the combined risk of heart attack, stroke and death in high-risk patients with type 2 diabetes; and the PERISCOPE trial, which is studying the effects of ACTOS on progression or regression of atherosclerosis in the coronary arteries using intravascular ultrasound.”

About ACTOS
ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.

Additional Information
ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.

Do not take ACTOS if you have active liver disease. Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood glucose.
-more-

Takeda Pharmaceuticals North America, Inc.
Based in Lincolnshire, Ill., Takeda Pharmaceuticals North America, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. In the United States, Takeda currently markets oral diabetes, insomnia, cholesterol-lowering and gastroenterology treatments, and through the Takeda Global Research & Development Center, Inc. the company has a robust pipeline with compounds in development for diabetes, cardiovascular disease and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about the company and its products, visit www.tpna.com.

Posted by dlife at 01:51 PM | Comments (0)

UF Study Sheds Light on Cystic Fibrosis-Related Diabetes

Gainesville, Fla., July 6, 2006 (Eurekalert) - A growing number of cystic fibrosis patients are battling a second, often deadly complication: a unique form of diabetes that shares characteristics of the type 1 and type 2 versions that strike many Americans.

Many of these patients are teens who take enzymes to help digest their food and undergo daily physical therapy to loosen the thick, sticky mucus that clogs their lungs. But despite treatments that are helping thousands to live decades longer than ever before, when diabetes strikes, their life expectancy plummets -- on average by two years for men and an astounding 16 for women.

Now a University of Florida study in animals suggests diabetes in cystic fibrosis patients is not caused by the destruction of insulin-producing cells in the pancreas -- as is often the case in patients with the traditional form of type 1 diabetes -- but by differences in how these cells function. The findings were published this month in the American Diabetes Association's journal Diabetes.

Cystic fibrosis patients with diabetes produce some insulin on their own, but they require daily injections to boost their levels when eating so they can properly use sugar and other food nutrients for energy. At times they also become very resistant to the insulin they do make, similar to people with type 2 diabetes.

"For the longest time, the development of diabetes in cystic fibrosis has been thought to be chronic destruction of pancreas, so eventually you get loss of the insulin-producing beta cells," said Michael Stalvey, M.D., an assistant professor of pediatrics at UF. "Our study provides some early evidence to suggest there is an inherent difference in beta cell function."

Cystic fibrosis patients suffer recurrent episodes of infection and inflammation that slowly destroy the lungs. The pancreas is also affected, interfering with proper digestion. The disease stems from a faulty gene that blocks the normal passage of salt and water through the body's cells. It is this gene deficiency that is proposed to cause insulin-producing cells to malfunction, Stalvey said.

About 30,000 Americans have cystic fibrosis, making it the nation's most common lethal hereditary disorder. On average, they will not live past 35, though some are living through their 40s and even into their 60s. As each year passes, the likelihood they will develop diabetes increases. As many as 16 percent of all patients with cystic fibrosis also have diabetes, a number that is expected to rise as overall life expectancy for cystic fibrosis patients increases. Half will show signs of diabetes by age 30 and will suffer a rapid decline in overall health and lung function, muscle mass and body mass index.

"It's becoming more and more frequent because of the increasing age of patients," Stalvey said. "That's part of the reason why new recommendations call for screening patients 14 years and older yearly with an oral glucose tolerance test. Each year we know their likelihood of developing diabetes gets higher and higher.

"These young people, teenagers or young adults in their early 20s, have been fighting all their lives to stay healthy and keep their nutrition up," he added. "Now they've just been given something that potentially will overwhelm them. It's a huge thing for them, given the consequences that diabetes means to their underlying condition."

In the UF study, researchers developed the first animal model for the study of cystic fibrosis-related diabetes. They used mice that scientists from the University of North Carolina engineered to be missing the gene that makes the protein responsible for transporting salt and water across the cell membrane. People with cystic fibrosis have a mutated form of this protein.

UF scientists administered a low dose of a chemotherapy drug that weakened insulin-producing cells but did not destroy them. They then tested the animals' ability to regulate their blood sugar while fasting and after receiving glucose, simulating the rise in blood sugar that occurs after eating food.

Animals with the protein deficiency were more sensitive to the effects of the chemotherapy drug and had more difficulty regulating blood sugar levels, both while fasting and after receiving glucose. Mice that were still able to produce the crucial protein that prevents cystic fibrosis were able to maintain normal blood sugar levels, even after the drug had damaged some of their insulin-producing cells.

"This goes beyond improving our understanding of patients with cystic fibrosis-related diabetes; it also will help us improve our understanding of other forms of diabetes and help us work on strategies for a future cure," Stalvey said.

"Twenty-five percent of adolescents and 40 percent of adults with cystic fibrosis have diabetes, and diabetes is associated with poorer survival in this population," said Antoinette Moran, M.D., division head of pediatric endocrinology and director of the Pediatric Diabetes Program at the University of Minnesota Medical School. "The cause of cystic fibrosis-related diabetes is not completely understood, but it is clearly different from other forms of diabetes. The study by Stalvey and colleagues is important because it is the first to show that there are intrinsic abnormalities in the insulin-producing cells of the pancreas related to the genetic defect that causes cystic fibrosis."

Posted by dlife at 01:06 PM | Comments (0)

Fat-Generated Hormone Drives Energetic Capacity of Muscle

July 5, 2006 (Eurekalert)- The fat-generated hormone adiponectin plays an important role in the energetic capacity of skeletal muscle, according to a new study in the July, 2006, Cell Metabolism, published by Cell Press. Adiponectin is unusual among fat hormones in that its levels generally decline in those who are obese.

The researchers report evidence in people and mice, linking low adiponectin levels to insulin resistance and reductions in the number of "cellular power plants" called mitochondria in skeletal muscle. The findings suggest that therapies designed to boost the adiponectin signal might prove beneficial for the treatment of insulin resistance and diabetes, they said.

"We have discovered a skeletal muscle pathway by which adiponectin increases mitochondrial number and function and exerts antidiabetic effects," said lead author Anthony Civitarese from Pennington Biomedical Research Center in Baton Rouge, Louisiana.

Mitochondria utilize nutrient components, including fats and carbohydrates, to generate usable energy. The number of mitochondria therefore influences the way that muscles function. For example, people who exercise regularly have more mitochondria in their muscles than do those who are sedentary.

Earlier studies found that obese individuals and those with type 2 diabetes have reduced adiponectin concentrations, the researchers said. The new study examined the effects of that reduced adiponectin on skeletal muscle.

The researchers first examined children whose parents had type 2 diabetes and those with no family history of the disease. Muscle taken from individuals prone to diabetes was insulin resistant and had lower than normal concentrations of mitochondrial enzymes, suggesting some dysfunction, they found. The level of adiponectin also correlated with the estimated number of mitochondria in the muscle samples.

Further study of adiponectin-deficient mice similarly found that the animals were resistant to insulin and exhibited deficits in mitochondria in their skeletal muscles.

Finally, the researchers showed that adiponectin treatment of human muscle tissue in culture sparked the production of mitochondria. The treatment also limited the production of harmful free radicals, or reactive oxygen species, a sign that the mitochondria were operating more efficiently.

The current findings, together with earlier studies that showed that adiponectin increases glucose uptake from the blood stream, suggest that the hormone might have therapeutic potential for those with insulin resistance or type 2 diabetes, Civitarese said.

However, adiponectin itself is difficult to produce in the quantities that would be required for a drug, he added.

"It may be that a mimetic drug that acts like adiponectin might prove beneficial," he said.

Posted by dlife at 01:11 PM | Comments (0)

Mutation in Tumor Suppressor Gene Causes Pancreatic Islet Cells to Reproduce

Cancer biology discovery could lead to new diabetes treatments

(Philadelphia, PA) July 5, 2006 (Eurekalert) - Researchers at the University of Pennsylvania School of Medicine have found that the acute loss of a protein called menin can cause the proliferation of pancreatic islet cells, which secrete insulin to regulate blood sugar. The menin gene (Men1) mutation in humans causes an inherited disease called Multiple Endocrine Neoplasia type 1 (MEN1). Not only could this discovery inform basic cancer biology, it also has implications for treating Type 1 diabetes. The researchers report their findings in the latest issue of Cancer Research.

MEN1 patients develop mostly benign tumors or hyperplasia (over proliferation of cells) in several endocrine organs, such as parathyroids and pancreatic islet cells. Normally, the menin protein has a tumor-suppressing or cell-proliferation-suppressing function. Loss of menin can cause proliferation of pancreatic islet cells, but not the adjacent exocrine cells that secrete proteins other than insulin.

The researchers developed an animal model that allowed for precise timing in "cutting" the Men1 gene from the genome of knock-out mice. They showed that within seven days of excising Men1, pancreatic islet cells proliferated in the mice. Previously, other labs could only see proliferating islet cells after months of Men1 excision because they could not precisely time the process. "Our results show an acute effect of Men1 excision and directly link Men1 to repression of pancreatic islet cell proliferation," says senior author Xianxin Hua, MD, PhD, Assistant Professor of Cancer Biology at Penn's Abramson Family Cancer Research Institute.

The researchers excised Men1, the gene encoding the protein menin, from both islet cells and adjacent exocrine cells in the pancreas, but only in islet cells did they observe cells proliferating. This is important because Men1 mutations largely cause endocrine hyperplasia or tumors, but not exocrine tumors. "Our results showing preferential effects on islet-cell proliferation could at least in part explain that the loss of menin only leads to endocrine tumors," explains Hua.

In type I diabetes, the loss of islet beta cells is the leading reason why a sufficient amount of insulin cannot be produced. "If we could eventually repress menin function to specifically stimulate beta-cell proliferation, this may facilitate devising new strategies to increase insulin-secreting beta cells and treating diabetes," notes Hua.

"We did not expect the connection between a study about a tumor suppressor and a potential new avenue for treating diabetes," he adds. "By taking advantage of studying a genetically well-characterized tumor syndrome, MEN1, we set out to understand how the first step of benign tumor development is precisely controlled. The more we discovered about menin function, the better we understood the precise role of menin in regulating islet cell proliferation. This latest finding about the acute and specific role of menin on repressing islet cells, but not adjacent exocrine cells, led to the realization that manipulating the menin pathway might be a powerful way to stimulate islet cell proliferation to fight type I diabetes, although we are just beginning toward that goal."

Study co-authors are Robert B. Schnepp, Ya-Xiong, Haoren Wang, Tim Cash, Albert Silva, Alan Diehl, and Eric Brown, with participation from the members of Dr. Eric Brown's lab and Dr. Alan Diehl's lab, all from Penn. This research was funded by the National Institutes of Health.

Posted by dlife at 01:09 PM | Comments (0)

Higher Levels of Obesity Associated With Greater Health Risks

The health risks for women who are extremely obese may be underestimated as a new study indicates they have a higher prevalence of hypertension, diabetes, and high cholesterol than women at lower levels of obesity, according to a study in the July 5 issue of JAMA.

July 4, 2006 (Newswise) — The health risks for women who are extremely obese may be underestimated as a new study indicates they have a higher prevalence of hypertension, diabetes, and high cholesterol than women at lower levels of obesity, according to a study in the July 5 issue of JAMA.

Obesity diagnosis and treatment are typically based on body mass index (BMI) of at least 30. BMI is calculated as weight in kilograms divided by height in meters squared. However, three categories of obesity are defined: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (40 and greater). (A 5’4” person would have a BMI of 40 if they weighed 233 lbs). The latter 2 categories, sometimes termed severe obesity, are reported to be increasing especially rapidly in the United States, according to background information in the article. From 1986 to 2000, prevalence of BMI of 30 or higher approximately doubled, while that of BMI of 40 or higher quadrupled and that of BMI of 50 or higher increased 5-fold. In 2000, 2.8 percent of all U.S. women, and 6 percent of black women reported measurements consistent with extreme obesity. Estimates of obesity-related risks in women have generally been based on weight data that preceded the increase in extreme obesity. It has been unclear whether health risk increases or plateaus as body weight increases throughout the obese range.

Kathleen McTigue, M.D., M.S., M.P.H., of the University of Pittsburgh, and colleagues conducted a study to examine the relationship between weight category and risk of death and coronary heart disease (CHD) in a large population-based sample of U.S. women, focusing on risk across degree of obesity. The researchers analyzed data on incident death and cardiovascular outcomes by weight status in 90,185 women recruited from 40 U.S. centers for the Women’s Health Initiative-Observational Study who were followed-up for an average of 7.0 years (Oct. 1993 to Aug. 2004).

The researchers found that extreme obesity prevalence differed with race/ethnicity, from 1 percent among Asian and Pacific Islanders to 10 percent among black women. “In this diverse population-based sample of older women, we found that obesity was linked with considerable health risk and that accounting for degree of excess weight is important in understanding weight-related health risk. Overall, extremely obese women were more likely to die over the average 7.0 years of follow-up than were women in other examined weight categories. Modeling analyses adjusted for age, smoking status, educational achievement, U.S. region, and physical activity level showed that weight-related risk for all-cause mortality, CHD mortality, and CHD incidence did not differ by race/ethnicity.”

“There was a positive trend in all-cause mortality risk and CHD incidence with increasing weight category. This trend had borderline significance for CHD mortality among black women, likely reflecting sample size limitations. Much of the obesity-related mortality and CHD risk was mediated by diabetes, hypertension, and hyperlipidemia [high cholesterol levels]. In white women, as other studies have found, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women. Smoking may modify weight-related risk in black women, but further study is needed to understand the nature of this relationship,” the authors write.

“Our findings have important clinical and policy implications. The escalating prevalence of extreme obesity may exacerbate the health effects and health-related expenditures

Posted by dlife at 01:14 PM | Comments (0)

Infections Link with Diabetes, Suggests Biggest Study Yet

July 3, 2006 (Eurekalert) - A major study has added weight to the theory that environmental factors such as common infections may be a trigger for diabetes in children and young adults.

The study, the biggest of its kind, analysed information from a register of over 4,000 people aged 0-29 years old diagnosed with Type 1 diabetes over a 25-year period. The findings for young adults have not been published before.

A quarter of a million people in the UK have Type 1 diabetes, and the number of cases in children is rising by three per cent each year. It develops if the body is unable to produce any insulin and usually appears before the age of 40.

The study authors, from Newcastle and Leeds Universities and Leeds Teaching Hospitals NHS Trust, carried out a sophisticated statistical analysis using information from the register on the times and places where the children and young adults were diagnosed.

A pattern emerged where 'clusters' of cases were found at different geographical locations and time intervals for 10-19 year olds. There were six to seven per cent more cases of Type 1 diabetes found in 10-19 year olds in the clusters than would have been expected by chance.

Females with the condition were more likely to occur in clusters with seven to 14 per cent more cases than expected found in young girls and women aged 10-19 years.

This pattern, which experts call 'space-time clustering', is typical of conditions triggered by infections. Conditions caused by more constant environmental factors produce clusters of cases in one place over a much longer time period.

The results are published in the academic journal Diabetologia and should help towards understanding more about the causes of Type 1 diabetes.

It has previously been suggested that infections are linked to the development of Type 1 diabetes in children who are genetically susceptible to certain environmental triggers.

Lead study author, Dr Richard McNally, of Newcastle University's School of Clinical Medical Sciences (Child Health) said: "This research brings us closer to understanding more about Type 1 diabetes. However, it's just one piece in the jigsaw and much more research is needed before we can identify which infections may be to blame and thus inform advice on preventative measures.

"The condition is likely to be caused by an interplay of factors, of which infections are just one element."

The study used data on 4008 0-29 year olds from the Yorkshire Register of Diabetes in Children and Young People* from 1978-2002, which receives funding from the Department of Health.

Dr Richard Feltbower, Co-researcher and Research Statistician from the Paediatric Epidemiology Group at the University of Leeds said: "This research is based on a unique register of patients diagnosed with Type 1 diabetes and the results for young people are entirely new. The clusters may occur as a result of infections precipitating the condition in already predisposed individuals."

Simon O'Neill, Director of Care and Policy at Diabetes UK, said: "We always suspected that common infections could be a trigger for Type 1 diabetes in those who are already genetically susceptible. This research provides vital evidence in supporting this link.

"The fact that the number of cases of Type 1 diabetes is rising by three per cent each year cannot be explained by genetics alone. This research reinforces the idea that common infections and environmental factors also play a part."

FACTS AND FIGURES: (provided by Diabetes UK)

* There are two types of diabetes - Type 1 and Type2.
* The number of children with Type 1 diabetes has increased by three per cent per year in the UK over the last 40 years.
* The incidence of diabetes in the UK has doubled every 20 years since 1945
* There are around 250,000 people with Type 1 diabetes in the UK
* There are 20,000 UK children aged under 15 with diabetes (most will have Type 1)
* The peak age for diagnosis of Type 1 diabetes in the UK is 10-14 years but is becoming younger with a steep rise in children under five. Nearly all people with Type 1 diabetes are diagnosed by the time they are 40.

Posted by dlife at 01:18 PM | Comments (0)

Obesity Associated with Psychiatric Disorders, Decreased Odds of Substance Abuse

July 3, 2006 (Eurekalert) - Obesity is associated with a 25 percent increase in the risk of developing mood and anxiety disorders and a 25 percent decrease in likeliness for substance abuse, according to a paper in the July issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

About 31 percent of all U.S. adults were obese in 2000, an increase from 23 percent in 1990, according to background information in the article. Obese adults are at higher risk of diabetes, cardiovascular disease and other harmful conditions. Previous studies have suggested a link between obesity and depression, but little research has examined the associations between obesity and other psychiatric disorders.

Gregory E. Simon, M.D., M.P.H., of the Group Health Cooperative, Seattle, and colleagues studied 9,125 adults from across the country who were interviewed as part of a large national survey of mental disorders between Feb. 5, 2001, and Feb. 12, 2003. Participants (average age 44.8 years) completed an in-home interview that included questions about demographic characteristics, height, weight and psychiatric disorders. These included mood disorders, such as major depression, dysthymia (persistent mild depression with associated symptoms) and bipolar disorder; anxiety disorders, such as panic disorder and generalized anxiety disorder; and substance abuse disorders, including alcohol or drug dependence.

Of all the participants, 6,795 had a body mass index (BMI) of less than 30 and 2,330 had a BMI of 30 or greater and were therefore considered obese. Those who were obese had a higher prevalence of mood and anxiety disorders and a lower prevalence of substance abuse disorders over their lifetimes. These associations remained similar for men and women. The link between obesity and mood disorders appeared strongest in non-Hispanic whites and in those with higher education levels.

"The estimated prevalence of lifetime mood disorder in those with BMIs below 30 and in those with BMIs 30 or higher translates to a population-attributable risk of 24 percent, which indicates that nearly one-quarter of the cases of obesity in the general population are attributable to the association with mood disorder," the authors write. "This calculation illustrates the public health importance of the association but does not indicate a direction for the causal relationship. It is equally correct to state that more than one-fifth of cases of mood disorder in the general population are attributable to the association with obesity." Increased appetite, weight gain, reduced physical activity and binge eating have all been associated with depression, potentially increasing risk for obesity. However, obesity could also contribute to depression by limiting physical activity, or through the stigma that may be associated with being overweight, especially among some women and other particular sociodemographic groups. An unknown third cause also could be linked to both. The results also do not indicate the mechanisms behind the negative association between obesity and substance abuse.

"We conclude that obesity is meaningfully associated with a range of common mood and anxiety disorders in the general U.S. population," the authors write. "Obesity is associated with a moderately lower risk of substance use disorder. Variation in the obesity-depression relationship by education level and race/ethnicity suggests an important role of social or cultural factors in mediating or moderating the relationship between obesity and mood disorders."

Posted by dlife at 12:45 PM | Comments (0)