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VIVUS Announces Positive Results From Two Phase 3 Studies; Obese Patients on Qnexa Achieve Average Weight Loss up to 14.7% and Significant Improvements in Co-Morbidities

2009-10-09T20:47:32Z

September 9, 2009 (VIVUS) - VIVUS, Inc. (Nasdaq: VVUS) today announced positive results from two final, phase 3 pivotal 56-week studies, EQUIP (OB-302) and CONQUER (OB-303), evaluating the safety and efficacy of Qnexa(TM), an investigational drug, in more than 3,750 patients across 93 sites. The EQUIP and CONQUER studies met all primary endpoints by demonstrating statistically significant weight loss with all three doses of Qnexa, as compared to placebo. Patients taking Qnexa also achieved significant improvements in cardiovascular and metabolic risk factors including blood pressure, lipid levels, and type 2 diabetes.

The outstanding results from the EQUIP and CONQUER studies, in addition to the results from EQUATE that were reported late last year, confirm the positive effect of Qnexa and underscore the important role this therapy may play in the lives of patients battling obesity and related co-morbidities, if approved by the FDA," stated Leland Wilson, president and chief executive officer of VIVUS. "The results of the phase 3 program, designed and executed after Special Protocol Assessments were completed by the FDA, exceed the FDA benchmarks for clinically significant weight loss. The results support the company's plan to file a New Drug Application with the FDA by the end of 2009 and submit the results from the studies for publication in peer-reviewed journals. We believe these results may provide a compelling opportunity for global pharmaceutical companies, and we intend to initiate partnering discussions now that we have the full data set in hand."

Wilson added, "We are proud of the results of our Qnexa phase 3 program, and I would like to thank Dr. Thomas Najarian, the inventor of Qnexa, the entire development team at VIVUS, Dr. David Orloff and his staff at Medpace, the clinical research organization that managed these studies, and the clinical investigators and patients who participated in the Qnexa clinical trials."

Qnexa is a proprietary formulation and unique dosing regimen that combines two well known pharmaceutical therapies - phentermine and topiramate - to create a novel, patented therapy. The phase 3 program evaluated three doses of Qnexa (numbers reflect milligrams of phentermine and controlled release topiramate, respectively):

-- Qnexa 15/92 (full dose)
-- Qnexa 7.5/46 (mid dose)

-- Qnexa 3.75/23 (low dose)

"The weight loss observed with Qnexa in these two one-year, double-blind, randomized trials far exceeds the weight loss observed for other agents reported in literature," said Kishore Gadde, MD, director of obesity clinical trials at Duke University and a lead investigator. "The efficacy and safety results confirm the earlier findings of our phase 2 study, which showed a very good efficacy and benefit/risk profile. Importantly, the medical benefits of this treatment in reducing the risk of weight-related co-morbidities such as hypertension, diabetes, and dyslipidemia could establish Qnexa as a major advancement in the management of obesity."

EQUIP (OB-302) Results

The EQUIP study included 1,267 morbidly obese patients (1,050 females and 217 males) across 93 centers in the United States. The average baseline BMI of the study population was 42.1 kg/m(2) and baseline weight was 256 pounds. Patients had a 4-week dose titration period followed by 52 weeks of treatment. The study was a randomized, double-blind, placebo-controlled, 3-arm, prospective trial with patients randomized to receive once-a-day treatment with low-dose Qnexa, full-dose Qnexa or placebo. Patients were asked to follow a hypocaloric diet representing a 500-calorie/day deficit and advised to implement a simple lifestyle modification program. Results from the study are as follows:

-- Average weight loss for Qnexa patients completing the EQUIP study was 37
pounds and 18 pounds with full-dose Qnexa and low-dose Qnexa,
respectively, as compared to 6 pounds in the placebo group;
-- 60% of the full-dose Qnexa patients who completed the study lost at
least 10% of their baseline weight;
-- 43% of the full-dose Qnexa patients who completed the study lost at
least 15% of their baseline weight;
-- Completion rate for EQUIP was 47%, 57%, 59% for patients taking placebo,
low-dose Qnexa and full-dose Qnexa, respectively; and

-- Patients treated with full-dose Qnexa had significant improvements in
blood pressure, triglycerides and cholesterol.

CONQUER (OB-303) Results

The CONQUER study included 2,487 overweight and obese patients (1,737 females and 750 males) with high blood pressure, high cholesterol or type 2 diabetes across 93 centers in the United States. The average baseline BMI of the study population was 36.6 kg/ m2 and baseline weight was 227 pounds. Patients had a 4-week dose titration period followed by 52 weeks of treatment. The study was a randomized, double-blind, placebo-controlled, 3-arm, prospective trial with patients randomized to receive once-a-day treatment with mid-dose Qnexa, full-dose Qnexa or placebo. Patients were asked to follow a hypocaloric diet representing a 500-calorie/day deficit and advised to implement a simple lifestyle modification program. Results from the study are as follows:

-- Average weight loss for Qnexa patients who completed the CONQUER study
was 30 pounds and 24 pounds with full-dose Qnexa and mid-dose Qnexa,
respectively, as compared to 6 pounds in the placebo group.
-- In the CONQUER study subset analysis, higher risk patients, defined as
those in the upper 25th percentile of a specific co-morbidity, who were
treated with full-dose Qnexa for 56 weeks achieved the following changes
in cardiovascular risk factors:
-- Reduction in systolic blood pressure of 20 mmHg from 147 mmHg at
baseline, as compared to a reduction of 14 mmHg in the placebo group
(p<0.0001). This improvement occurred in the presence of a
significant reduction in blood pressure medications in Qnexa-treated
patients as compared to placebo;
-- Reduction in triglyceride levels of 98 mg/dL from 268 mg/dL at
baseline, as compared to a decrease of 42 mg/dL from 262 mg/dL at
baseline in the placebo group (p<0.0001);
-- Reduction in hemoglobin A1c levels of 0.6% from 7.3% at baseline as
compared to a reduction of 0.1% from 7.4% at baseline for the
placebo patients (p<0.0001). These improvements occurred in the
presence of a significant reduction in antidiabetic medications in
Qnexa-treated patients compared with placebo. All patients were
treated to standard of care for type 2 diabetes. 64% of the
full-dose Qnexa patients who completed the study lost at least 10%
of their baseline weight;
-- 39% of the full-dose Qnexa patients who completed the study lost at
least 15% of their baseline weight; and

-- Completion rates for CONQUER were 57%, 69%, 64% for patients taking
placebo, mid-dose Qnexa, and full-dose Qnexa, respectively.

Across both 56-week studies comprised of more than 3,750 patients, the most commonly reported side effects were dry mouth, tingling, constipation, altered taste and insomnia. Monthly assessments using prospective psychometric instruments in accordance with FDA's guidance showed no signal for suicidality risk. There were no suicide attempts or suicidal behaviors, and there was no signal for suicidal ideation across all treatment groups including placebo. Depression or depressed mood adverse events of a moderate to severe nature were less than 2% and were similar among patients in the Qnexa and placebo groups. Overall, depression scores, quality of life including self esteem and general health significantly improved for patients on Qnexa.

"I have seen dramatic and sustained weight loss with Qnexa as well as notable improvements in cardiovascular risk factors, diabetes, emotional well being and quality of life in my patients," commented Michelle Look, M.D., FAAFP, of the San Diego Sports Medicine and Family Health Center and a lead investigator in the studies. "What is so striking for me is how many of my patients were able to achieve weight loss with Qnexa for the first time after many years of battling weight problems without success. The excellent tolerability of Qnexa allowed patients to stay on therapy for a year, as evidenced by the strong completer rates."

Other Safety Studies

VIVUS completed a thorough QT prolongation (TQT) study evaluating subjects taking Qnexa. The study was completed with no signal for QT prolongation. Subjects taking Qnexa also underwent complex and extensive cognitive and psychomotor testing using validated, FDA accepted testing methodologies. There was no clinically significant change in overall cognitive function or effect on psychomotor skills seen in patients taking Qnexa.

"These data are significant, and when coupled with my own experience treating patients with Qnexa, clearly demonstrate that it is one of the promising pharmaceutical therapies in development to assist patients in achieving significant weight loss," stated Louis Aronne, MD, Clinical Professor of Medicine and Director of the Comprehensive Weight Control Program at New York-Presbyterian Hospital/Weill Cornell Medical Center and one of the investigators involved in the clinical trials. "People with weight problems have a truly biologic disease, and we are in desperate need of more options and effective tools to help our patients combat this disease and the other serious medical conditions that arise as a result of weight gain. I am encouraged by the efficacy and safety seen in these late stage Qnexa trials."

Narrow Window of Opportunity to Reverse Obesity with Surgery in Teens

2009-10-09T18:15:58Z

October 9, 2009 (Newswise) - According to a recent study of clinical characteristics of teens who underwent laparoscopic Roux-en-Y gastric bypass surgery from 2002 until 2007, doctors may have a much narrower window of opportunity to reverse morbid obesity in teens than previously thought.

The study, conducted at Cincinnati Children’s Hospital Medical Center, appears in the current online edition of the Journal of Pediatrics.

The study focused on 61 teens who underwent laparoscopic Roux-en-Y gastric bypass at Cincinnati Children’s. The results of the study showed that one year after the study, BMI in the overall group of teens pre-surgery decreased by 37 percent, however because of their starting weights, the teens were still considered to be morbidly obese. This means that doctors can predict what a patient’s weight will be one-year post weight loss surgery.

Lead author of the study, Thomas Inge, MD, PhD, Associate Professor of Surgery and Pediatrics, explains that "Current guidelines for adolescent weight loss surgery suggest that we begin to consider surgery only after a teen is 80-100 percent overweight. Our new data show that when we intervene when a patient is between 100 and 150 percent over ideal weight, we can expect successfully resolution of obesity. But by the time the teen is 200 percent over their ideal weight for age, the surgery will reduce their weight substantially, but many of the patients will still remain morbidly obese.

This is the first study in adolescents to specifically show that the postoperative weight is strongly influenced by the patient’s starting weight. This finding raises a concern that waiting until children are super obese to begin to think of surgery may result in major weight loss, but not resolution of obesity and certain medical problems than intervening at an early stage of the disease. For instance, in those who remain significantly obese following surgery, this excess weight can have negative effects on joints and mobility; the long-term risks of remaining seriously overweight are unknown.

Co-author Dr. Stavra Xanthakos, Assistant Professor of Pediatrics and pediatric gastroenterologist feels that, “We [doctors] have to do a better job of identifying teens who are gaining enormous amounts of weight quickly and get help for them earlier.” Dr. Xanthakos says that when doctors or parents notice that a teen is beginning to gain weight rapidly, there should be a staged approach to managing the weight problem. “If the weight gain is not effectively stopped with initial nutritional or exercise measures, then even more intensive treatments or programs are indicated, and ultimately some very serious thought has to be given to surgery,” said Dr. Xanthakos.

Prior to weight loss surgery, teens with extreme obesity present with the most significant and global impairments in quality of life relative to other pediatric chronic illness populations and rates of depressive symptoms that are 3-4 times higher than national rates, says pediatric psychologist and co-author Dr. Meg Zeller, Associate Professor of Pediatrics. “We cannot underestimate the psychological impact on the adolescent when obesity progresses to such extreme levels and is not durably treated.” In fact, Zeller’s recent data (published in the journal Obesity) from the same group of teens demonstrated significant psychosocial improvements following surgery at one-year. “As we learn more about the benefits of surgery in this age group, it pushes the medical community to ask when is the optimal time to intervene surgically and potentially change a young person’s developmental course in a more positive direction?”

Mary L. Brandt, MD, Professor and Vice Chair of the Michael E. DeBakey Department of Surgery and a pediatric surgeon at Texas Children’s Hospital worries about these results as well. “We are trying to help teenagers who are at high risk for preventable but life-threatening diseases such as diabetes or obesity induced liver disease. Bariatric surgery will improve the medical condition of obese teenagers regardless of the starting weight of the patient. But our ability to help these children prevent or reverse their life-threatening diseases will be even greater if our patients are able to approach a normal weight.”

According to Brandt, “The other major implication of this new data is that many insurance companies will delay surgery for years, usually by requiring documentation of multiple attempts at weight loss. Severely obese teenagers only rarely respond to these kinds of treatments and, despite intense efforts to lose weight, often will gain weight during these efforts. Although it is ethically important for these children to have a least one well supervised attempt to lose weight without surgery, this report shows us that delaying the surgery while trying multiple times may not be in their best interest.”

This study, like others, found that after surgery, patients generally show significant improvement or resolution of cardiovascular risk factors such as blood pressure, cholesterol, and triglyceride levels.
Dr. Inge said that the study indicates that families and communities need to take childhood weight problems seriously and aggressively pursue the best treatment options available for them before the weight problem gets out of hand. “As doctors who take care of kids, we have an obligation to identify those patients who are at highest risk and start explaining treatment options to families earlier before the child or teen gets to be two or three times his or her ideal weight, " said Dr. Inge.

Common Herbicides and Fibrate Drugs Block Nutrient-sensing ‘Taste’ Receptor Found in Gut and Pancreas

2009-10-09T16:15:09Z

October 9, 2009 (Newswise) - According to new research from the Monell Center and the Mount Sinai School of Medicine, certain common herbicides and lipid-lowering fibrate drugs act in humans to block T1R3, a nutrient-sensing taste receptor also present in intestine and pancreas.

Commonly used in agriculture and medicine, these chemical compounds were not previously known to act on the T1R3 receptor.

The T1R3 receptor is a critical component of both the sweet taste receptor and the umami (amino acid) taste receptor. First identified on the tongue, emerging evidence indicates that T1R3 and related taste receptors also are located on hormone-producing cells in the intestine and pancreas.

These internal taste receptors detect nutrients in the gut and trigger the release of hormones involved in the regulation of glucose homeostasis and energy metabolism.

“Compounds that either activate or block T1R3 receptors could have significant metabolic effects, potentially influencing diseases such as obesity, type II diabetes and metabolic syndrome,” noted Monell geneticist and study leader Bedrich Mosinger, M.D., Ph.D.

In the study, published online in the Journal of Medicinal Chemistry, researchers tested the ability of two classes of chemical compounds to block the T1R3 receptor. The compounds – fibrates and phenoxy-herbicides – were selected based on their strong structural similarity to lactisole, a sweet taste inhibitor that exerts its taste effects by blocking T1R3.

Fibrates are a class of drugs frequently used to treat lipid disorders such as high blood cholesterol and triglycerides. Phenoxy-herbicides are used in agriculture to control broad-leaf weeds; the best known, 2,4-D, is one of the most extensively used herbicides worldwide.

Using an in vitro preparation, the researchers found that both classes of compounds potently blocked activation of the human sweet taste receptor, acting at micromolar concentrations to inhibit binding of sugars to the T1R3 component of the receptor.

Additional testing revealed that the inhibitory effect of both fibrates and phenoxy-herbicides on the T1R3 receptor is specific to humans. That is, the ability of these compounds to block the receptor did not generalize across species to the rodent form of the receptor.

Mosinger commented on the implications of the findings and noted the importance of testing chemicals intended for human use on human tissues. “The metabolic consequences of short- and long-term exposures of humans to phenoxy-herbicides are unknown. This is because most safety tests were done using animals, which have T1R3 receptors that are insensitive to these compounds,” he said.

The ability of fibrate drugs to interact with T1R3 receptors also was previously unknown. The study findings suggest that these receptors might be an important pharmacological target of first-generation fibrates, such as clofibrate, which were believed to act on a different receptor to affect lipid metabolism. Newer fibrate drugs are more specific for the second receptor and interact less with the T1R3 receptor.

Mosinger points out that little is known about how T1R3 blockade affects hormone levels and metabolism. “Given the number of compounds used in agriculture, medicine and the food industry that may affect human T1R3 and related receptors, more work is needed to identify the health-related effects of exposure to these compounds,” he said.

Also contributing to the study were first author Emeline Maillet from the Department of Neuroscience at Mount Sinai School of Medicine and co-author Robert Margolskee of Monell.

Gluten-Free Diet Reduces Bone Problems in Children with Celiac Disease

2009-10-08T18:49:15Z

October 8, 2009 (EurekAlert) - Celiac disease (CD) is an inherited intestinal disorder characterized by life-long intolerance to the ingestion of gluten, a protein found in wheat, rye, and barley. Although CD can be diagnosed at any age, it commonly occurs during early childhood (between 9 and 24 months). Reduced bone mineral density is often found in individuals with CD. A new article in the journal Nutrition Reviews examines the literature on the topic and reveals that a gluten-free diet can affect children's recovery.

Metabolic bone disease remains a significant and common complication of CD. Reduced bone mineral density can lead to the inability to develop optimal bone mass in children and the loss of bone in adults, both of which increase the risk of osteoporosis. There also exists an additional risk of fracture in people with CD.

However, evidence suggests that a gluten-free diet (GFD) promotes a rapid increase in bone mineral density that leads to complete recovery of bone mineralization in children. A GFD improves, although rarely normalizes, bone mineral density in adults. Children may attain normal peak bone mass if the diagnosis is made and treatment is given before puberty, thereby preventing osteoporosis in later life.

Also, nutritional supplements consisting of calcium and vitamin D seem to increase the bone mineral density of children and adolescents with CD.

"Our findings reinforce the importance of a strict gluten-free diet, which remains the only scientific proven treatment for celiac disease to date," the authors conclude. "Early diagnosis and therapy are critical in preventing celiac disease complications, like reduced bone mineral density."

UF Study: Exercise Improves Body Image for Fit and Unfit Alike

2009-10-08T17:08:40Z

October 8, 2009 (EurekAlert) - Attention weekend warriors: the simple act of exercise and not fitness itself can convince you that you look better, a new University of Florida study finds.

People who don't achieve workout milestones such as losing fat, gaining strength or boosting cardiovascular fitness feel just as good about their bodies as their more athletic counterparts, said Heather Hausenblas, a UF exercise psychologist. Her study is published in the September issue of the Journal of Health Psychology.

"You would think that if you become more fit that you would experience greater improvements in terms of body image, but that's not what we found," she said. "It may be that the requirements to receive the psychological benefits of exercise, including those relating to body image, differ substantially from the physical benefits."

The study by Hausenblas and graduate student Anna Campbell is the first to systematically analyze the wide-ranging effects of exercise on body image by examining all intervention studies on the subject until June 2008. From the 57 publications, the researchers found conclusively that exercise buffed up the way people see their bodies regardless of the actual benefits, but the results varied.

Negative body image has grown to almost epidemic proportions in the past 20 years, with as many as 60 percent of adults in national studies saying they don't like the way their bodies look, Hausenblas said.

Americans spend billions of dollars a year for products designed to change their body size and shape, including diet pills and various cosmetic procedures, she said.

"Body dissatisfaction is a huge problem in our society and is related to all sorts of negative behavior including yo-yo dieting, smoking, taking steroids and undergoing cosmetic surgery," she said. "It affects men and women and all ages, starting with kids who are as young as five years old saying they don't like how their bodies look."

The psychological advantages of exercise have been less explored, including the reduction of depression or confidence in body image, compared with the well-researched and understood physical benefits, she said.

The study found no difference in body image improvement between people who met the American College of Sports Medicine guidelines by exercising at least 30 minutes a day five days a week and those who did not, Hausenblas said. The guidelines are considered the minimum amount of exercise needed to receive the health related benefits of physical activity, she said.

"We would have thought that people exercising this amount would have felt better about their bodies than those who did not work out as much," she said.

In other results, the study showed slightly larger benefits from exercise in terms of improving body image for women than men, Hausenblas said.

"We believed the gap would be much bigger, but what could be coming into play is the rise of body image issues among men," she said. "We're seeing more media portrayals of the ideal physique for men rather than the overriding emphasis on women we did in the past."

Age presented another difference, with older people most likely to report enhanced body images from exercise, Hausenblas said. The gap may be explained by the older generation having more concerns about their body image than young people, who tend to exercise more, she said.

While the frequency of exercise mattered for boosting body perceptions, there were no differences for the duration, intensity, length or type of exercise, the study found.

"People who say they have high body dissatisfaction tend to exercise the least, so we wanted to take it a step further and see whether exercise causes people's body image to improve," she said.

Kathleen Martin Ginis, a kinesiology professor at McMaster University in Ontario, Canada, and exercise expert, praised the research. "This is an important study because it shows that doing virtually any type of exercise, on a regular basis, can help people feel better about their bodies," she said. "With such a large segment of the population dissatisfied with their physiques, it's encouraging to know that even short, frequent bouts of lower intensity exercise can improve body image."

CHEO RI Study Uses Sophisticated Genetic Engineering to Improve Insulin-Producing Beta Cells

2009-10-07T15:56:58Z

October 7, 2009 (EurekAlert) - One of the biggest mysteries about diabetes is why specialized cells in the pancreas stop secreting insulin, which the body needs in order to store glucose from food. A team from the Children's Hospital of Eastern Ontario (CHEO) Research Institute has identified a protein that inhibits insulin production in mice - work that offers a new way of understanding, and perhaps of one day treating, both Type 1 and Type 2 diabetes.

A study to be published today in the leading international journal Cell Metabolism describes how a research group led by Dr. Robert Screaton, who holds the Canada Research Chair in Apoptotic Signaling at the University of Ottawa, used sophisticated genetic engineering to remove or 'knock out' the Lkb1 gene from beta cells of laboratory mice. The result was an increase in both the size and number of beta cells, as well as greater amounts of insulin stored and released by the cells.

Importantly, the improved beta cell function lasted for at least five months, even in mice fed a high-fat diet designed to mimic the high caloric intake associated with Metabolic Syndrome and Type 2 diabetes in humans.

"We were surprised by the impressive accumulation of Lkb1 in beta cells of diabetic mice, which suggested that Lkb1 might contribute to their impaired function. After removal of the Lkb1 gene, the beta cells grow larger, proliferate more, and secrete more insulin. It's a one-stop shop for the much needed insulin", said Dr. Screaton.

"The knockout mice on a high-fat diet have lower blood glucose. If this observation is confirmed in humans, it may give us another clue into the development of Type 2 diabetes, and perhaps new treatment options".

"Type 1 and 2 diabetes, already common diseases, are showing disturbingly steady growth in incidence. The two conditions are among Canada's, and indeed the globe's, greatest health challenges," said Dr. Alex MacKenzie, CEO of the CHEO Research Institute and a physician who treats children with diabetes at CHEO. "The findings of Dr. Screaton's team introduce a novel and unanticipated potential therapeutic avenue for this costly and serious condition. It is some of the most important work to come out of our institute."

Monash Research Cautions Against Use of Antioxidants

2009-10-07T14:51:20Z

October 7, 2009 (Newswise) - An international team of scientists, led by Monash University researchers, has found that anti-oxidants commonly touted for their health-promoting benefits, could contribute to the early onset of Type 2 diabetes.

The team, led by Professor Tony Tiganis from the Monash Department of Biochemistry and Molecular Biology, has found that molecules known as Reactive Oxygen Species (ROS) may play a protective role in the early stages of Type 2 diabetes by enhancing insulin action. Anti-oxidants prevent the beneficial effects of ROS.

The team showed that when ROS levels were elevated in muscles of genetically-modified mice they could prevent the onset of insulin resistance and diabetes that is induced by a high-fat diet.

However when these animals received anti-oxidants, which 'mop up' ROS, the improved insulin response was lost and the mice became more 'diabetic'.

The findings, published today in the prestigious journal Cell Metabolism, challenge the widely-held view that ROS are always harmful and that anti-oxidants are always beneficial.

"ROS molecules, such as hydrogen peroxide, are important for normal cell function. We have shown that ROS present in muscle enhance insulin action and help lower blood sugar levels," Professor Tiganis said.

"However, our studies do not negate the role of ROS in late-stage disease. There's a 'yin and yang' relationship that takes place, wherein ROS are beneficial in the early stages of Type 2 diabetes and shift to being harmful at later stages of the disease. We are now trying to find out when ROS make the switch from being 'good' to 'bad'.

"Although we need to undertake further studies in humans, our results indicate that the widespread use of anti-oxidants by the general public as a preventative measure is something that should be discouraged, particularly if you are otherwise healthy," Professor Tiganis said.

"Eat healthy and exercise as this is a natural source of ROS that promotes insulin action."

Diabetes is Australia's fastest growing disease, with an estimated 275 people developing the disorder each day. Type 2 diabetes, which is linked to genetic and lifestyle factors including obesity, low physical activity and poor diet, costs our health care system an estimated $3 billion dollars annually.

Professor Tiganis led a team of 12 Monash researchers, scientists from the Baker IDI Heart and Diabetes Institute, University of Melbourne, and Cold Spring Harbor Laboratory in the US.

Good Nutritional Control May Prevent Polyneuropathy After Bariatric Surgery

2009-10-07T14:42:30Z

October 7, 2009 (Newswise) - With the rising popularity of bariatric surgery (BS), there is an increasing need for patients and their doctors to recognize and prevent the potential complications from this weight loss procedure. Neurological complications are one of the risks, and recent studies show that appropriate preventative measures and a multidisciplinary approach can largely prevent the development of postoperative nerve damage, also known as peripheral neuropathy (PN).

In previous studies, researchers showed that PN can occur after bariatric surgery and be of three types: mononeuropathy, sensory predominant polyneuropathy, and radiculoplexus neuropathy. Malnutrition was the major risk factor for sensory predominant polyneuropathy but not the other subtypes.

Nutritional deficiencies can occur following BS due to patients not taking multi vitamins, experiencing more weight loss than expected, and post operative complications.

The authors performed a retrospective, cohort study in all patients having BS at a select clinic between 1985 and 2002, with follow-up. Potential risk factors were analyzed using life table methods. Of 393 eligible patients with BS, 26 (7%) developed PN. The authors observed the same three patterns of PN found previously; the majority were mononeuropathies (21 patients, 81%). Univariate life table analysis showed the following risk factors: increased serum glycosylated hemoglobin and triglycerides, prolonged duration of hospital stay, postoperative gastrointestinal symptoms, as well as nausea and vomiting. PN occurred less frequently and specifically the sensory predominant polyneuropathy subtype occurred less frequently than in a prior cohort.

As described by researcher, Dr. P. James B. Dyck, neurologist at Mayo Clinic in Rochester, Minnesota, “At Mayo Clinic, we insist that patients eligible for bariatric surgery undergo nutritional consultations, and a psychiatric assessment prior to surgery to make certain their nutrition is addressed. Patients attend nutritional clinics 6 months prior to surgery and multivitamins are taken by all patients scheduled to undergo this procedure.” Fellow researcher, Dr. Pariwat Thaisetthawatkul added, “This is a message of prevention, this study really emphasizes this. Patients should be aware that PN is a risk of BS and seek their care where there is a multidisciplinary approach to their treatment. Surgeons performing this procedure should include the nutritionists and endocrinologist on staff and get them involved with the patient care. Through a systematic, multidisciplinary approach of intensive pre- and postoperative nutritional management and frequent follow-up of patients undergoing BS, the development of this type of neuropathy can largely be prevented.”

The complete findings and results of this study are being presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 56th Annual Meeting in San Diego, California, at the Manchester Grand Hyatt, October 7-10, 2009. With over 5000 members, the AANEM is the world’s largest organization dedicated to advancing neuromuscular, musculoskeletal, and electrodiagnostic medicine.

Strong Link Between Obesity and Depression

2009-10-07T14:39:16Z

October 7, 2009 (Newswise) - Doctors should pay more attention to the link between common mental illness and obesity in patients because the two health problems are closely linked, according to researchers at the University of Adelaide.

In an editorial published today in the British Medical Journal (BMJ), the Adelaide researchers add support to claims of a two-way risk between obesity and common mental disorders.

The editorial makes comments on a new research paper on this topic published in the same issue of the BMJ by Professor Mika Kivimäki from University College London.

"A better understanding of the mechanisms for the apparent bi-directional risk between obesity and common mental disorders is needed for effective treatment and prevention," says the lead author of the editorial, Dr Evan Atlantis from the University of Adelaide's School of Medicine.

"Although the topic is largely unexplored, several psychosocial, lifestyle and physiological factors may be involved in the complex inter-relationship between obesity and mental illness," he says.

"Obese people - especially those who perceive themselves as being overweight - often experience weight-related stigma and discrimination, and consequently present with symptoms of low self esteem, low self worth, and guilt. Obesity is associated with socioeconomic disadvantage and low levels of physical activity, both of which are strong predictors of depression.

"Obesity may constitute a chronic stressful state, which in turn can cause significant physiological dysfunction. Such dysfunction would then predispose individuals to depressed mood and associated symptoms," he says.

Dr Atlantis says reduced physical activity and overeating - "particularly comfort foods rich in fats and sugars to improve mood" - are common among depressed and anxious patients.

"Activation of the endocannabinoid system, which increases appetite and may simultaneously alleviate depression, is likely to reinforce this eating behavior. Socioeconomic disadvantage may further exacerbate the over-consumption of comfort foods because of their low cost," he says.

Dr Atlantis says patients presenting to their doctor with symptoms of common mental disorder should be assessed for obesity and related chronic diseases, and vice versa.

"A multidisciplinary approach that focuses on promoting a healthy lifestyle is important. Further research on how best to deliver lifestyle interventions is needed, along with government action on taxes, tariffs, and trade laws to encourage the supply and consumption of healthy food and physical activity choices," he says.

Immune Cell Entry Into the Pancreatic Islets Key to Understanding Type 1 Diabetes Origins

2009-10-06T17:22:38Z

October 6, 2009 (Newswise) - St. Jude Children’s Research Hospital investigators have discovered how destructive immune cells gain access to insulin-producing cells and help cause diabetes.

The finding points to possible new strategies to halt or prevent type I diabetes.

Working in mice, researchers demonstrated that to enter key areas of the pancreas known as the islets of Langerhans, immune cells known as T cells must recognize a marker on the surface of insulin-producing cells housed there. T cells play a key role in regulating immune response. Once inside the islets, T cells trigger the inflammation that can lead to destruction of the insulin-producing beta cells.

The result is type I diabetes.

The report answers a fundamental question about the role of T cell entry and accumulation in the islets in development of type I disease, a disease that affects as many as 3 million Americans. The research appears in the October 16 edition of the journal Immunity. Dario Vignali, Ph.D., is the paper’s senior author and vice chair of the St. Jude Immunology department.

The St. Jude results contradict a widely held theory that only a small percentage of T cells that infiltrate the islets were actively involved in causing type I diabetes. The old scenario held that most of the T cells found in the islets were recruited to the site by a small number of specialized T cells. Those recruited or bystander T cells were thought to play no role in causing diabetes. Furthermore, it was thought that any T cell could gain access to the islets.

“The new research argues that every T cell in the islet is important. What these T cells recognize that allowed them to gain access to the islets may provide us with clues as to what might be needed to prevent diabetes,” Vignali said.

“Understanding the molecular differences between the T cells in the islets and the T cells in the periphery might also start to tell us a lot about what it takes to make a T cell attack the beta cells and cause diabetes.”

Without insulin to turn food into fuel for cells, patients develop type I diabetes and are left dependent on insulin injections, an insulin pump or in rare cases a pancreas transplant. Unlike the more common form of the disease, known as type II diabetes, type I diabetes usually affects children and is sometimes called juvenile diabetes. About 15,000 new cases are diagnosed annually in the United States. Even with treatment, patients with type I diabetes are at risk for blindness, kidney failure and other complications.

“This paper also presents a new clinical intervention strategy—blocking T cells from even getting into the islet cells in the first place,” Vignali added.

If any T cell could enter the islets, then it would be less likely that there were any “special rules” for entering islets and thus nothing unique about entry into the islets that might be targeted by treatment, he explained.

Understanding how T cell access to islets is controlled also raises hopes for developing a therapy to re-educate the immune system to tolerate rather than attack the beta cells. The St. Jude research points to a new route into islet cells.

For this study, scientists used a technique Vignali’s laboratory developed in 2006. The technique allows researchers to quickly modify T cell production in mice. Normally mice make millions of T cells that can recognize many different cells and microorganisms. Each T cell carries on its surface a receptor that recognizes and binds to just one specific antigen, or marker, on the surface of the T cell’s intended target.

The modification technique allowed researchers to create strains of mice with only two types of T cells, each with different receptors. One population carried a receptor that recognized the insulin-producing beta cells and could cause diabetes. The other group was programmed to recognize a different antigen. Researchers reported they could not induce the latter group of T cells to enter the islets.

Then investigators created and tracked T cells with three types of receptors—receptors from T cells with a proven ability to enter islet cells and cause diabetes, those able to enter islets and cause inflammation, but not diabetes, and a third group of receptors with no connection to type 1 diabetes or islet cells. The scientists reported that none of the T cells, even those with a demonstrated ability to cause diabetes in mice, could induce bystander T cells to enter the islet cells.

Finally, investigators tracked T cells carrying receptors from mice that naturally developed type I diabetes. They created mice with 17 new T cell receptors, five from the spleen of diabetic mice and 12 from T cells isolated in the islets of those diabetic mice. If the islets control T cells entry, then islets in the new mouse strains would be infiltrated by T cells with islet-derived, but not spleen-derived, receptors.

That is what happened. “About 70 percent of the receptors that came from the islets could mediate T cell migration back into the islets, while none of the receptors that came from the spleen could do likewise,” Vignali said. The islet-derived receptors were also linked to rapid development of diabetes, with one-third causing diabetes during the 10-week study.

Vignali said it is unclear if the findings will hold true for other autoimmune diseases, such as rheumatoid arthritis or Crohn’s disease. The authors noted that the structure, location and other factors might make the islet cells unique.

Greig Lennon, Maria Bettini and Amanda Burton, of St. Jude, shared first authorship on this study. The other authors were Erica Vincent and Paula Arnold of St. Jude, and Pere Santamaria of the University of Calgary, Alberta, Canada.

The work was supported in part by the Juvenile Diabetes Research Foundation International, the National Institutes of Health and ALSAC.

Chinese Herbal Medicines for Preventing Diabetes in High Risk People

2009-10-06T15:00:36Z

October 6, 2009 (EurekAlert) - More research is required to establish whether Chinese herbal medicines can reduce the likelihood of developing diabetes, according to Cochrane Researchers. Although herbal medicines are widely used in Asian countries to treat pre-diabetes (impaired glucose tolerance or IGT), the precursor of the disease, researchers say there is still not enough hard scientific evidence to confidently recommend their use.

"People with impaired glucose tolerance are more likely to develop full blown diabetes and it may be possible to prevent or delay the onset of the disease through lifestyle changes and medication. Chinese herbal medicines have been used for this purpose for a long time, so there is plenty of anecdotal evidence for their safety and effectiveness, but we were interested to find out whether scientific research could provide a basis for recommending these alternative treatments," says lead researcher, Suzanne Grant of the Centre for Complementary Medicine Research at the University of Western Sydney in Australia.

Pre-diabetes is recognised by higher than normal blood sugar levels. People with pre-diabetes are advised to change their diets to control their blood glucose levels and prevent progress to diabetes. In China, Korea and Japan herbal pills, teas and powders have been used for a long time to treat pre-diabetes and diabetes. They are thought to work in a number of different ways to help normalise blood sugar levels, including by improving pancreatic function and increasing the availability of insulin, a hormone that regulates blood sugar levels.

The researchers considered data from 16 clinical trials including 1,391 people who received 15 different herbal formulations. According to their findings, combining herbal medicines with lifestyle changes is twice as effective as lifestyle changes alone at normalising patients' blood sugar levels. Those given the herbal formulations were less likely to develop full blown diabetes during the study period. Trials included in the review lasted from one month to two years. No adverse effects were reported in any of the trials.

"Our results suggest that some Chinese herbal medicines can help to prevent diabetes, but we really need more research before we can confidently say that these treatments work," says Grant. "The real value of the study is as guidance for further trials. We need to see more trials that make comparisons with placebos and other types of drugs, and better reporting on the outcomes of these trials."

Bulimia, Binge Eating Respond to Talk Therapy

2009-10-06T14:46:57Z

October 6, 2009 (Newswise) - Although most people with bulimia and binge eating disorders wait many years before seeking help, a new review shows that psychological treatment can make a large difference — and that cognitive behavioral therapy (CBT) is the most effective talk therapy for these disorders.

People with bulimia experience cycles of disordered eating behavior in which they overeat and then purge, often by self-induced vomiting or taking laxatives. Binge eating disorder includes bouts of overeating, but without purging, and researchers have linked it to obesity.

Eating disorders are most common in women, with bulimia affecting about 1 percent of women and binge eating disorder affecting 2 percent to 5 percent. Although bulimia rates appear stable, binge eating disorder increasingly is becoming common.

The review included 48 studies with 3,054 participants and strengthened earlier findings in favor of cognitive behavioral therapy. It found that 37 percent of people completely stopped binge eating when given CBT focused on binging — while 3 percent of those assigned to a waiting list control group quit.

Other therapies were less successful than CBT, helping 22 percent of participants achieve abstinence
from binging by the end of treatment. One approach called interpersonal therapy did achieve comparable results — but took months longer to do so.

Lead author Phillipa Hay, M.D., is foundation chair of mental health at the University of West Sydney in Australia. “Cognitive behavioral therapy is really the treatment of choice,” she said. “It has far and away the best evidence. It hadn’t really been so definitively found in previous reviews.”

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

Cynthia Bulik, Ph.D., is director of the University of North Carolina Eating Disorders Program at Chapel Hill. Bulik, who had no connection with the review, said the key findings are that “bulimia nervosa is treatable; that some treatment is better than no treatment; that CBT is associated with the best outcome for bulimia nervosa.”

The original intent of CBT was to treat depression. A modified type of CBT in the studies focuses specifically on binge eating disorder symptoms. Nonetheless, participants also experienced significant improvements in mood.

“Many people have problems with depression secondary to binge eating disorders,” Hay said. “They often feel anxious and guilty because of their binging so if the eating disorder improves, the depression improves as well. We did look at the effects of CBT [for binge eating] on depression and it does help depression significantly just in itself.”

Weight, however, did not change with treatment. “None of these psychotherapies really affect people’s weight, which is good thing for people with bulimia who are normal weight but for those who are overweight or obese, they will need weight-loss therapies as well,” Hay said.

Cognitive behavioral treatment of bulimia or binge eating disorder typically involves 15 to 20 outpatient sessions with a therapist over a five-month period. CBT works by helping patients change the way they think about their behavior.

“CBT rests on the premise that unhealthy thoughts lie at both the roots of bulimia nervosa and in the maintenance of unhealthy eating behaviors,” Bulik said. “The goals of CBT are first to have the patient become his or her own detective and — via self-monitoring — start to understand their patterns of binge eating and purging and recognize and anticipate the cues (triggers) for their unhealthy behaviors.” Once these patterns and the thoughts that drive them are identified, they can be challenged and addressed.

Hay gave the example of someone who, after binging, skips lunch and breakfast the following day. That can easily produce another binge because the craving caused by intense hunger is harder to resist. The therapist would help the patient see that eating healthy meals after a binge would break the cycle, even though fasting might initially seem like a better solution.

The review also compared CBT done in conjunction with a therapist to self-help using books that teach its techniques and tactics. While guided CBT was more effective, there was not much research on self-help and Hay says the approach is “promising” and that it should receive further study. There has been more research on bulimia than binge-eating disorder—so more data would help clarify the best approaches to the latter.

Other studies have found that antidepressants can help fight bulimia and binge eating. While this review did not compare medication to psychotherapy, Hay says clinicians should try CBT first because more people stick with it. “The dropout rate is quite significantly higher with drugs,” she says.

“Some treatment is better than none,” Bulik said. “If you can’t find a therapist [who practices CBT for binge eating], don’t throw in the towel— find another kind of therapist, pick up a self-help book, do something because the outcome will be better than doing nothing at all.”

Los Angeles Fast-Food Restaurant Ban Unlikely to Cut Obesity, Study Finds

2009-10-06T14:35:28Z

October 6, 2009 (EurekAlert) - Restrictions on fast-food chain restaurants in South Los Angeles are not addressing the main differences between neighborhood food environments and are unlikely to improve the diet of residents or reduce obesity, according to a new RAND Corporation study.

Researchers from RAND Health found that the South Los Angeles region has no more fast-food chain establishments on a per capita basis than other parts of the city, but rather many more small food stores and other food outlets.

Those outlets are more likely to be the source of high-calorie snacks and soda consumed substantially more often by residents of South Los Angeles as compared to other parts of the city, according to the study published online by the journal Health Affairs.

"The Los Angeles ordinance may have been an important first by being concerned with health outcomes, but it is not the most promising approach to lowering the high rate of obesity in South Los Angeles," said Roland Sturm, the study's lead author and a senior economist at RAND, a nonprofit research organization. "It does not address the main differences we see in the food environment between Los Angeles neighborhoods nor in the diet of residents."

The Los Angeles City Council in August 2008 approved a ban on opening or expanding fast-food restaurants in an area of the city known as South Los Angeles. The ordinance focused on fast food restaurants characterized by "excessive signage, little or no landscaping, large expanses of surface parking, drive-through windows, multiple driveways, parking lots fronting the street" and argued that the low-income region had a higher concentration of fast-food establishments than more-affluent sections of the city.

But an analysis by Sturm and study co-author Dr. Deborah Cohen found that South Los Angeles actually has a lower concentration of fast-food chain restaurants than other parts of the city.

Researchers found there were about 19 fast-food chain restaurants per 100,000 residents in South Los Angeles, while there were 29 per 100,000 people in affluent West Los Angeles and 30 per 100,000 residents for all of Los Angeles County. There are significantly fewer restaurants of any type per person in South Los Angeles compared to Los Angeles County overall, according to the study.

In contrast, the density of small food stores was about double that of the county average and more than three times the number in West Los Angeles. This was partially offset by a lower density of large supermarkets in South Los Angeles.

Researchers also analyzed information from a survey of 1,480 adults from across Los Angeles County that asked residents about their food purchases and habits of eating out. The results showed that adults in South Los Angeles consumed significantly more "discretionary" calories from sugary or salty snacks and soft drinks compared with residents of wealthier neighborhoods.

Residents of South Los Angeles and residents of more-affluent areas reported eating similar amounts of fruits and vegetables each day and had fairly similar levels of physical activity, although residents of South Los Angeles did report watching more television.

Researchers say their work suggests that focusing on the sources of snack calories would address the differences between South Los Angeles and other parts of Los Angeles better than the current ban on new fast-food establishments.

"The ubiquitous availability of food can be overwhelming and stimulate hunger and cravings for food, regardless of whether an individual has a physiological need for nutrition," Cohen said. "Research has made it clear that frequency and saliency of food cues in the environment, the type of foods available, and the portion sizes served, are key issues that effective policies need to address."

One of the goals of the Los Angeles regulation is the creation of more sit-down restaurants, but in terms of diet, this is not necessarily an improvement, according to researchers.

"There is a misconception that sit-down restaurants provide 'healthier' food and are less likely to lead to obesity," Sturm says. "However, when we looked at some common offerings, an average lunch sandwich in a sit-down restaurant had more than the combined calories of three Big Mac hamburgers; many dinner choices have over 2,000 calories and cover the energy needs for a full day. And that does not even include possible appetizers or desserts."

The study also found that residents of South Los Angeles and those from wealthier areas reported eating out in restaurants at about the same frequency, although South Los Angeles residents are more likely to purchase items from a food cart or mobile vender and less likely to eat in a sit-down restaurant.

While residents of South Los Angeles and those from more-affluent areas seem to shop at similar types of stores, there was one dramatic difference -- many South Los Angeles residents walk or take public transit to the market, something seldom done in higher-income areas.

Future Diabetes Treatment May Use Resveratrol to Target the Brain

2009-10-06T14:26:43Z

October 6, 2009 (Newswise) - Resveratrol, a molecule found in red grapes, has been shown to improve diabetes when delivered orally to rodents. Until now, however, little has been known about how these beneficial changes are mediated in the body. A new study accepted for publication in Endocrinology, a journal of The Endocrine Society, shows that the brain plays a key role in mediating resveratrol’s anti-diabetic actions, potentially paving the way for future orally-delivered diabetes medications that target the brain.

Resveratrol activates sirtuins, a class of proteins that are thought to underlie many of the beneficial effects of calorie restriction. Previous studies in mice have provided compelling evidence that when sirtuins are activated by resveratrol, diabetes is improved. Sirtuin activators are now being tested in humans as anti-diabetic compounds.
Sirtuins are expressed virtually everywhere throughout the body and until now, little has been known about what tissues mediate resveratrol’s beneficial effects. Knowing where in the body the beneficial effects of activated sirtuins are mediated could help in the development of more effective targeted diabetes medications.
“We know that sirtuins are expressed in parts of the brain known to govern glucose metabolism, so we hypothesized that the brain could be mediating resveratrol’s anti-diabetic actions,” said Roberto Coppari, PhD, of the University of Texas Southwestern Medical Center and co-author of the study. “To test the hypothesis, we assessed the metabolic consequences of delivering resveratrol directly into the brain of diabetic mice. We found that resveratrol did activate sirtuins in the brain of these mice which resulted in improving their high levels of blood sugar and insulin.”
“These findings may lead to new strategies in the fight against type 2 diabetes,” said Coppari. “By knowing that the brain mediates resveratrol’s anti-diabetic actions, industry can now focus on developing sirtuin activators that directly target the brain. When orally-delivered, these drugs will likely improve diabetes without affecting the other organs in which activation of sirtuins may not always be beneficial.”
Other researchers working on the study include Giorgio Ramadori, Laurent Gautron, Teppei Fujikawa, Claudia Vianna and Joel Elmquist of the University of Texas Southwestern Medical Center in Dallas, Tex.

The article, “Central administration of resveratrol improves diet-induced diabetes,” will appear in the December 2009 issue of Endocrinology.

Ethnic Background May Be Associated with Diabetes Risk

2009-10-06T14:23:46Z

October 6, 2009 (Newswise) - Fat and muscle mass, as potentially determined by a person’s ethnic background, may contribute to diabetes risk, according to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

Obesity, a worldwide health concern, is associated with increased insulin resistance, type 2 diabetes and cardiovascular disease. The prevalence of obesity is increasing in all populations across the globe, yet past research has found that body fat distribution varies widely among different ethnic groups. Researchers in this study investigated which ethnic groups were most likely to be at increased risk for diabetes due to higher total body fat and lower muscle mass.

“We know certain ethnic backgrounds show significant differences in amounts of body fat and lean mass,” said Scott Lear, PhD, of Simon Fraser University in Vancouver, Canada and lead author of the study. “What we didn’t know, until now, is if these differences are related to insulin levels and insulin resistance, and therefore lead to an increased risk for diabetes. Our findings indicate they are.”

In this study, researchers measured insulin levels and compared the amount of total body fat to lean mass in 828 men and women of Aboriginal, Chinese, European and South Asian origin to determine how differences in fat mass and lean mass may be related to insulin levels and insulin resistance in each group. Of the four ethnic groups studied, South Asians were found to have both higher fat mass, lower muscle mass and greater insulin levels, placing them at increased risk for insulin resistance and diabetes.

“An individual’s ethnic background may determine the amount of body fat and lean mass they have, and therefore may also be associated with diabetes risk,” said Lear. “In populations at increased risk for diabetes, interventions that reduce fat mass and increase muscle mass, such as caloric restriction and regular exercise should be investigated.”

Other researchers working on the study include Simi Kohli of Simon Fraser University in British Columbia, Canada; Gregory Bondy of the University of British Columbia in Canada; Andre Tchernof of Laval University Medical Research Centre in Laval, Canada; and Allan Sniderman of McGill Health Science Centre in Montreal, Canada.

The article, “Ethnic variation in fat and lean body mass and the association with insulin resistance,” will appear in the December 2009 issue of JCEM.