Joslin Study Shows Durability of Insulin Pump Therapy for Adolescents and Identifies Factors to Help Them Overcome Barriers to Success

BOSTON, October 31, 2006, (Joslin) -- In spite of its many advantages, there are many challenges to using an insulin pump to treat type 1 diabetes. Despite these challenges, however, more and more youngsters are choosing pump therapy, even though important questions remain about the pump's effectiveness for this age group: With all its risks and demands, is it a method of treatment that children and teens can maintain? What causes adolescents to go off of pump therapy and how often does this occur? Is it possible to identify those youth unable to meet the demands of pump therapy and to find interventions that will help them succeed?

Now, in the first long-term investigation conducted among pediatric patients who chose to go on pump therapy (rather than using it as part of a clinical trial), a new study in the November issue of Diabetes Care by researchers in the Pediatric, Adolescent, and Young Adult Section at Joslin Diabetes Center, is providing answers. Following a group of 161 children and adolescents, ages 4-21, for an average of four years, the researchers have shown that with proper training and follow-up, for the great majority of patients--more than 80 percent of the children in this study--insulin pump therapy provides a lasting and effective mode of treatment. They also identified several factors that put patients at risk for failure in adapting to pump use.

"More than 130 patients were able to use the pump effectively," says senior author, Lori Laffel, M.D., M.P.H., Chief of Joslin's Pediatric, Adolescent and Young Adult Section, an Investigator in the Genetics and Epidemiology Section and Associate Professor of Pediatrics at Harvard Medical School. "By looking at differences between the patients who remained on pump therapy and those who returned to injected insulin, we were able to identify factors present even at the start of pump therapy that were predictive of failure. For example, patients who resumed injection therapy checked their blood glucose levels less often from the start. Healthcare providers can use this information to provide more education, more psychosocial support, and more frequent visits directed at increasing blood glucose monitoring from the start of pump therapy to help kids to succeed."

"The fact that such a high percentage of patients succeeded proves that pump therapy is a viable mode of treatment for children and teens with type 1 diabetes," says the paper's lead author, Jamie Wood, M.D., Staff Physician and Research Associate at Joslin and Instructor of Pediatrics at Harvard Medical School. "Our job now is to overcome the barriers to pump therapy, so more patients can benefit from its advantages."

Starting on an insulin pump requires considerable training. Before beginning pump therapy, patients in the study and their families met with their healthcare team that included a pediatric endocrinologist, a nurse educator and a registered dietitian. The team taught them the mechanics of using and maintaining the pump, how to count carbohydrates, calibrate their insulin requirements and treat risks associated with pump therapy, such as site infections, diabetic ketoacidosis and hypoglycemia (low blood glucose levels). A mental health clinician also met with the children and their families to ensure they were ready to meet any challenges and to help them set up realistic expectations for ongoing diabetes management with the pump.

At three points during the study--the clinical visit just before starting on the pump, one year after initiation, and then at the study's close in January 2005--researchers gathered data on A1C levels (a measurement that indicates the average blood glucose over the past 2 to 3 months), rate of daily blood glucose monitoring and growth parameters (height, weight and body-mass index). These data also were monitored at the time of discontinuation for patients who stopped using the pump.

Examining the data associated with success and failure, the researchers observed several significant differences between the two groups of patients, one of which was present at the initiation of pump therapy. "We found that patients who were successful measured their blood glucose levels four or more times a day before they began pump therapy, while those who discontinued pump therapy measured them less," says Dr. Wood.

They also discovered that the patients who stayed on the pump had achieved better glycemic control than the patients who discontinued pump therapy. After the first year on pump therapy, the A1C levels of the group that succeeded dropped significantly. Although these levels subsequently rose to near the levels they were at the start of pump therapy, the group still was able to avoid the deterioration of blood glucose control that happens frequently among adolescents. Caused by such factors as increases in growth and puberty hormones, or the declining adherence to good health practices that occurs as they become more independent from their parents, deteriorating glucose control puts youth at greater risk for developing serious complications later in life. The youth in the group that succeeded also experienced decreased rates of hypoglycemia with pump therapy.

The patients who later resumed injection therapy, however, experienced rising blood glucose levels while they were on the pump. Furthermore, while the rate of severe hypoglycemia before beginning pump therapy was similar between the two groups, in the year following the start of pump therapy the patients who discontinued pump therapy experienced a significantly higher rate of severe hypoglycemic episodes.

"Our research suggests several approaches for improving success rates with pump therapy," says Dr. Wood. "When you evaluate if a person is ready to begin pump therapy, and you can see he or she is monitoring blood glucose levels only two or three times a day, you can suggest that the patient take some extra time to increase monitoring frequency before starting the pump. Or if you have a patient who doesn't show improvement in glycemic control in the first six months of pump therapy, you can try to find out what is interfering with success and help overcome any barriers. Our goal is not to determine which patients should be denied pump therapy, but to make it possible for more people to succeed with this remarkable tool."

Also participating in the study were Britta M. Svoren, M.D., Deborah A. Butler, M.S.W., L.I.C.S.W., and Lisa K. Volkening of Joslin, and Elaine C. Moreland, M.D., previously at Joslin and now at the University of Alabama and Children's Hospital, in Birmingham. The study was funded in part by the Katherine Adler Astrove Youth Education Fund, the Maria Griffin Drury Pediatric Endowment Fund and grants from the National Institutes of Health.

About Joslin Diabetes Center
Joslin Diabetes Center, dedicated to conquering diabetes in all of its forms, is the global leader in diabetes research, care and education. Founded in 1898, Joslin is an independent nonprofit institution affiliated with Harvard Medical School. Joslin research is a team of more than 300 people at the forefront of discovery aimed at preventing and curing diabetes. Joslin Clinic, affiliated with Beth Israel Deaconess Medical Center in Boston, the nationwide network of Joslin Affiliated Programs, and the hundreds of Joslin educational programs offered each year for clinicians, researchers and patients, enable Joslin to develop, implement and share innovations that immeasurably improve the lives of people with diabetes. As a nonprofit, Joslin benefits from the generosity of donors in advancing its mission. For more information on Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.

Posted by dlife at 03:08 PM | Comments (0)

Periodontal Therapy Helps Patients with Type 2 Diabetes

Japanese researchers find oxidative stress levels lower to those of nondiabetic patients

CHICAGO, October 31, 2006 (Eurekalert)- Patients with type 2 diabetes and periodontal disease who receive periodontal therapy see levels of oxidative stress, a condition in which antioxidant levels are lower than normal, reduced to the same levels as nondiabetic patients, according to a new study that appeared in the November issue of the Journal of Periodontology (JOP).

Researchers from Kyushu Dental College in Kitakyushu, Japan investigated the impact of periodontal therapy on patients with Type 2 diabetes, as compared to nondiabetic patients. They found that periodontal therapy decreased lipid peroxide (LPO), an oxidative stress index, in diabetic patients.

"Our research emphasized one of the benefits of having periodontal therapy for patients with diabetes," said Dr. Kazuo Sonoki, M.D. PhD at Kyushu Dental College, one of the study authors. "However, this was just a preliminary study and more research should be conducted to evaluate how periodontal disease affects both people with and without diabetes."

It has been found that diabetes and periodontal disease can lead to atherosclerosis, which occurs when deposits of fatty substances, cholesterol, and other substances build up in the inner lining of an artery. This buildup is called plaque. It has been thought that oxidative stress is linked to heart disease because oxidation of LDL (low-density lipoprotein) in the endothelium is a precursor to plaque formation. Recently, oxidative stress has emerged as an important factor for atherosclerosis in patients with diabetes.

"We hear every day about how more and more people are being diagnosed with diabetes," said Preston D. Miller, DDS and AAP President. "This research confirms that patients with diabetes should be especially conscious of their periodontal health. While more research needs to be done to evaluate the relationship between periodontal disease and diabetes, we do know that treating periodontal diseases can save teeth, and can promote overall health."

Posted by dlife at 01:56 PM | Comments (0)

The Lancet Publishes RIO-Diabetes Study[1]

Study Shows Rimonabant Significantly Improves Weight, Blood Sugar Levels and Other Cardiometabolic Risk Factors in People with Type 2 Diabetes

PARIS, France, October 27 (PRNewswire) - Sanofi-aventis announced today that the results of the RIO-Diabetes trial were posted on The Lancet online edition (publication in the print edition is expected shortly). The one-year trial showed that rimonabant 20 mg once daily significantly improved several cardiometabolic risk factors including weight, HbA1c (a measure of blood sugar control), HDL-cholesterol (good cholesterol) and triglycerides (fats in the blood), systolic blood pressure as well as waist circumference (a marker of intra-abdominal adiposity) in overweight / obese patients with type 2 diabetes uncontrolled with metformin or sulfonylurea. Importantly, over 50% of the improvements in HbA1c and HDL-cholesterol were independent of the weight loss achieved, suggesting a direct effect of rimonabant on these parameters.

"The RIO-Diabetes study showed that rimonabant 20 mg significantly improved weight, levels of blood sugar and other cardiometabolic risk factors important in the management of type 2 diabetes," said Professor André Scheen, Head of the Clinical Pharmacology, Division of Diabetes, Nutrition and Metabolic Disorders, Academic Hospital of Liège, University of Liège, Belgium, principal investigator of the RIO-Diabetes study and a member of the RIO programme steering committee. "The improved blood sugar control plus weight loss achieved with rimonabant is very encouraging. Today, most medications for type 2 diabetes are associated with weight gain and it is difficult for people with diabetes to lose weight and keep it off."

Among all patients who entered the RIO-Diabetes study, patients on rimonabant 20 mg once daily achieved an HbA1c reduction of 0.6% versus an increase of 0.1% on placebo from a baseline value of 7.3% and 7.2% respectively (p<0.0001 vs. placebo). Among those patients with a higher HbA1c (>8%), rimonabant 20 mg once daily achieved a reduction of 1.1%, compared with a reduction of 0.3% in the placebo group. Nearly 70% of patients treated with rimonabant 20 mg once daily lowered their HbA1c levels to below 7% as compared to only 48% of patients in the placebo arm (p<0.0001). Even more impressive, 43% of patients on rimonabant 20 mg once daily had HbA1c levels < 6.5% at their final visit compared to only 21% in the placebo group (p<0.0001). Approximately 57% of the reduction in HbA1c levels achieved with rimonabant 20 mg once daily was calculated to be independent of the weight loss achieved. The direct peripheral metabolic effects of rimonabant on other cardiometabolic risk factors has been demonstrated throughout the RIO clinical trial programme.[2,3,4]

"What is so significant about these findings is that rimonabant was able to reduce blood sugar levels in a patient population where further control or lowering is often difficult to attain. This is very important because for every 1% reduction in HbA1c there is an associated reduction of risk of 21% for any endpoint related to diabetes," said Professor Scheen.[5]

Patients treated with rimonabant 20 mg once daily benefited from a reduction in weight of 5.3 kg (11.7 lbs) versus 1.4 kg (3 lbs) for patients in the placebo group (p<0.001 vs. placebo). Waist circumference was reduced by 5.2 cm (2.05 in) in patients in the rimonabant 20 mg group versus 1.9 cm (0.7 in) observed in the placebo group (p<0.001).

HDL-cholesterol and levels of triglycerides were significantly improved in patients treated with rimonabant 20 mg once daily throughout the one-year period. Among all patients who entered the study, HDL-cholesterol increased by 15.4% in the rimonabant 20 mg once daily group versus 7.1% in the placebo group (p<0.0001). Furthermore, levels of triglycerides were reduced by 9.1% in patients treated with rimonabant 20 mg once daily compared to an increase of 7.3% in the placebo group (p<0.0001 vs. placebo). Approximately 57% of the increase in HDL-cholesterol achieved was not explained by weight loss alone and considered to be due to the direct effect of rimonabant (p<0.0001).

Rimonabant is the first selective CB1 receptor blocker which helps to reduce overactivity of the newly characterized endocannabinoid system (ECS). CB1 receptors, which form part of the ECS are located centrally in the brain, and peripherally in adipose tissue, liver, skeletal muscle, pancreas and the gastrointestinal tract. The ECS has been shown to play an important role in energy balance as well as being directly involved in fat and sugar metabolism.6 Peripherally, overactivation of the endocannabinoid system promotes fat accumulation at the level of adipose tissue and decreases glucose uptake in skeletal muscle; this can lead to increased risk of development of insulin resistance and impaired glucose tolerance. By blocking CB1 receptors in the brain and peripheral tissues, rimonabant results in a decrease in food intake, a loss of body weight, and direct improvements in cardiometabolic risk factors, such as blood sugars, HDL-cholesterol and triglycerides.

The RIO-Diabetes study also assessed the safety and tolerability of rimonabant 20 mg once daily, 5 mg once daily and placebo, the results of which were consistent with the data from the entire RIO clinical trial programme which involved more than 6,600 patients. Side effects were mainly mild, transient, self-limiting and occurred early in the treatment period. The most frequent side effects included nausea (12.1% for rimonabant 20 mg once daily vs. 5.7% for placebo), dizziness (9.1% for rimonabant 20 mg once daily vs. 4.9% for placebo), diarrhoea (7.4% for rimonabant 20 mg once daily vs. 6.6% for placebo), vomiting (5.9% for rimonabant 20 mg once daily vs. 2.3% for placebo), self-reported hypoglycaemia (5.3% for rimonabant 20 mg once daily vs. 1.7% for placebo), fatigue (5.3% for rimonabant 20 mg once daily vs. 3.7% for placebo) and anxiety (5.0% for rimonabant 20 mg once daily vs. 2.6% for placebo). Discontinuation rates due to adverse events were consistent with those reported in other trials in the RIO programme (15% for rimonabant 20 mg once daily vs. 5% for placebo, p<0.005). The most frequent adverse events leading to discontinuation were depressed mood disorders, nausea and dizziness.

Sanofi-aventis received an approvable letter for rimonabant from the U.S. Food and Drug Administration (FDA) in February 2006. In Europe, rimonabant, known as ACOMPLIA(R) is approved as an adjunct to diet and exercise for the treatment of obese patients (BMI equal or greater than 30kg/m2), or overweight patients (BMI>27kg/m2) with associated risk factors, such as type 2 diabetes or dyslipidaemia.

About the RIO-Diabetes Trial

RIO-Diabetes is a phase III, multinational, multi-centre, randomised, double-blind and placebo-controlled trial which compared two fixed-dose regimens of rimonabant (5 mg once daily and 20 mg once daily) to placebo for a period of one year. The study was conducted in 1,047 people with type 2 diabetes at 159 centres in 11 countries. Study participants were male and female between 18 and 70 years of age and had a BMI of between 27 kg/m2 and 40 kg/m2. Additional criteria included an HbA1c level between 6.5% and 10% and a fasting blood glucose level between 5.5 mmol/L (100 mg/dL) and 14.9 mmol/L (270 mg/dL).

The objectives of the trial were to assess the efficacy and safety of rimonabant in patients with type 2 diabetes already being treated with either metformin or sulfonylurea monotherapy. The study investigated the effect of rimonabant on HbA1c and other cardiometabolic risk factors. Safety and tolerability were also evaluated over the one-year treatment period.

The RIO-Diabetes trial is one of four phase III studies comprising the RIO programme, which assessed the efficacy and safety of rimonabant in cardiometabolic risk factor improvement and weight loss in over 6,600 overweight and obese patients studied worldwide. All four trials -- RIO-Diabetes, RIO-Lipids, RIO-Europe and RIO-North America -- in the phase III programme have been completed.

The results of the RIO-Diabetes trial were first presented at the Annual Scientific Session of the American Diabetes Association in June 2005.

About sanofi-aventis

Sanofi-aventis is the world's third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

Forward Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans" and similar expressions. Although sanofi-aventis' management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in sanofi-aventis' annual report on Form 20-F for the year ended December 31, 2005. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.

References:

[1] Scheen et al. Effect and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. The Lancet 2006. www.thelancet.com.

[2] Van Gaal et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. The Lancet 2005; 365: 1389-97.

[3] Despres J-P., Golay A., Sjostrom L, et al. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. New Engl J Med 2005; 353: 2121-34.

[4] Pi-Sunyer, X et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients RIO-North America: A Randomized Controlled Trial. JAMA 2006; 295: 761-775.

[5] Stratton IM, Adler AI, Neil HA, Matthews DR et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405-12.

[6] Di Marzo V, Matias I et al. Endocannabinoid control of food intake and energy balance. Nat Neurosci 2005; 8:585-9.

Posted by dlife at 12:14 PM | Comments (0)

New Tool Can Help Predict Diabetes Complications

Other Studies This Month: Coffee Helps Prevent Diabetes; When You Get Diabetes (Middle v. Old Age) Matters

October 25, 2006 (ADA) – A noninvasive tool that measures the skin’s autofluorescence could help doctors determine whether people with diabetes are beginning to develop serious complications, according to a study published in the November issue of Diabetes Care.

Researchers in the Netherlands found that illuminating a patient’s lower arm with a fluorescent tube accurately reflects vascular damage caused by the accumulation of advanced glycosylation end products (AGEs). AGEs are produced in the body when glucose links with protein. They play a role in damaging blood vessels, which can lead to complications, such as nerve damage.

Previous studies have shown that AGEs have fluorescent properties. This study confirmed that those properties could be measured by illuminating the skin, and that high levels of autofluorescence were associated with more severe diabetes complications, such as neuropathy, retinopathy and cardiovascular problems.

“With this tool, doctors could easily check people with diabetes in an outpatient clinic setting to see whether they may already be developing dangerous complications,” said lead researcher Dr. Helen Lutgers, of the University Medical Center in Groningen, the Netherlands. “The sooner complications are detected, the better the chance of preventing progression of damage.”

The technology used in this study is currently commercially available in Europe. Until FDA approval is obtained, its availability in the USA is restricted to experimental use only.

Posted by dlife at 10:47 AM | Comments (1)

Shorter Nightly Sleep in Childhood May Help Explain Obesity Epidemic

October 20, 2006 (Newswise) — Soaring levels of obesity might be linked to children sleeping fewer hours at night than they used to, claims a researcher in the Archives of Disease in Childhood.

Dr Shahrad Taheri of the University of Bristol, blames the increasing availability of computers, mobile phones, TVs and other gadgets on the diminishing nightly quota of sleep, and suggests they should be banned from children’s bedrooms.

Dr Taheri cites the emerging body of research on the impacts on the body of a fall in the nightly quota of sleep, which reflects circumstances in real life, rather than sustained sleep deprivation, which tends to be more extreme.

This research shows that shorter sleep duration disturbs normal metabolism, which may contribute to obesity, insulin resistance, diabetes, and cardiovascular disease. Even two to three nights of shortened sleep can have profound effects, the laboratory data suggest.

One study indicated that insufficient sleep at the age of 30 months was associated with obesity at the age of 7, suggesting that this could programme the part of the brain regulating appetite and energy expenditure, says Dr Taheri.

But it is also a problem for teenagers in whom the need for sleep increases during this critical developmental period, he says.

Another piece of research shows that levels of leptin, a hormone produced by fat tissue when energy stores are low, were more than 15% lower in those sleeping five hours compared with those clocking up 8.
Similarly, ghrelin, a hormone released by the stomach to signal hunger was almost 15% higher in those with a five hour sleep quota.

Sleep loss also disturbs other hormones, including insulin, cortisol (stress hormone), and growth hormone, says Dr Taheri, who adds that hormonal changes could boost the desire for carlorie rich foods.

And poor sleep sets up a vicious cycle. It leads to fatigue, which leads to reduced levels of physical activity….which leads to lower energy expenditure…..which leads to obesity, which itself leads to poor sleep, he adds.

Dr Taheri acknowledges that the mechanisms behind obesity are likely to be complex. “Sleep is probably not the only answer to the obesity pandemic, but its effect should be taken seriously, as even small changes in energy balance are beneficial,” he says.

“Good sleep could be promoted by removal of gadget distractions from bedrooms and restricting their use,” he suggests.

Posted by dlife at 11:37 AM | Comments (0)

Latest Weight-Loss Pill Offers Modest Results, Blocks ‘Munchies’

October 20, 2006 (Newswise) — A new drug billed as a magic bullet for obesity — rimonabant (Acomplia) — does help people lose weight, although not that much weight, and also helps lower cardiac risk factors, according to a review of studies.

Rimonabant went on sale in Europe in July, and U.S. approval is pending before the Food and Drug Administration. The drug works in a new way, suppressing the appetite by targeting the brain cells involved in the “munchies” familiar to marijuana users.

“The use of rimonabant after one year produces modest weight loss of approximately 5 percent” of body weight, found reviewers led by Cintia Curioni, at the State University of Rio de Janeiro, in Brazil. “Compared with placebo, a 20-milligram pill produced a 4.9 kilogram greater reduction in body weight in trials with one-year results.”

This translates to weight loss of a little under 11 pounds.

The review looked at four randomized controlled trials comparing rimonabant at two dosages and with placebo, after one or two years of treatment. Participants, all overweight or obese, followed a “mild” low-calorie diet, adjusted for individual body weight.

Only the higher dose — 20 milligrams — had significant impact on weight, waist circumference, cholesterol levels and blood pressure.

However, the higher dose brought on more, and more serious, side effects than both the lower dose and placebo.

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 rimonabant studies took place in 350 trial centers in the United States, Canada and Europe.

The 6,625 participants were at least 18 years old and overweight or obese. One study focused solely on people being treated for type 2 diabetes; another comprised people with high cholesterol or high blood pressure — important factors in heart disease risk .

The authors described the weight loss pattern: “After the 36th week, the level of weight loss decreased and the body weight was maintained practically until the end of the studies.” One study evaluated data after two years: “Patients who stayed on 20 mg rimonabant seemed to maintain their weight loss, while those who were re-randomized to placebo gained significant weight.”

People on the larger dose lost an average 1.5 inches on their waistlines. They also showed a slight dip in blood pressure. The higher drug dose significantly lowered blood lipids (fats) and increased high-density lipoprotein (“good” cholesterol) by 3.5 mg/dl compared to placebo.

But on the flip side, side effects included nausea, dizziness, headache, joint pain and diarrhea. More serious side effects included psychiatric and nervous system disorders.

Obesity drugs, which often come on the market with great fanfare, can end up being withdrawn in a flurry of lawsuits — like Fen/Phen — or simply produce underwhelming results for people expecting a magic bullet.
“Every time a new drug comes along, it gets a lot of attention. The natural course is that people who want it will try it, and people with have some lackluster results,” said Kelly Brownell, Ph.D., director of the Rudd Center for Food Policy and Obesity at Yale University.

“Few people lose enough weight to make themselves happy, more lose enough weight to get some medical benefit but overall results for most treatments for obesity are disappointing,” Brownell said.

Rimonabant has been billed for several years as a potential panacea for the most troublesome of habits – obesity, smoking and possibly alcohol addiction. Studies on its use in smoking-cessation studies are currently under way.

Curioni’s team compared its results to a previous review of orlistat and silbutramine, the only drugs approved in the United States for long-term obesity treatment:

“The weight loss associated with rimonabant was slightly greater compared to that related to silbutramine use, with more positive impact on cardiometabolic risk. The effects compared with orlistat appear to be greater weight loss and less frequent adverse effects.”

No head-to-head comparisons had been done at the time of the review.

The biggest difference may be in how rimonabant works, by blocking the cannabinoid receptors in the brain. Brownell called rimonabant’s ability to suppress munchies “an interesting finding. The issue of food and addiction hasn’t been explored very much; it should be.”

The review authors noted that the four reviewed studies were sponsored by Sanofi companies. With the studies all being sponsored by the drug-maker, results “probably represent a best-case scenario,” Brownell said.

None of the studies analyzed drug costs. “The fundamental problem is that even if one of these drugs caused significant weight loss, the cost would be so prohibitive that it wouldn’t be worthwhile on a public health basis,” Brownell said. “And only a few people would be able to afford them.”

Posted by dlife at 11:24 AM | Comments (2)

FTC and FDA Act Against Internet Vendors of Fraudulent Diabetes Cures and Treatments

October 20, 2006 (FTA) -The Federal Trade Commission (FTC) and the Food and Drug Administration (FDA), working with government agencies in Mexico and Canada, have launched a drive to stop deceptive Internet advertisements and sales of products misrepresented as cures or treatments for diabetes. The ongoing joint campaign has so far included approximately 180 warning letters and other advisories sent to online outlets in the three countries.

“We will continue working with our partners in the U.S. and internationally to make sure scammers have no place to hide,” said Lydia Parnes, Director of the FTC’s Bureau of Consumer Protection. “The Internet can be a great source of information, but it also is a billboard for ads that promise miracle cures for diabetes and other serious diseases. Our advice to consumers: ‘Be smart, be skeptical’ when evaluating health claims online.”

“We will not tolerate practices that raise false hopes and bilk consumers of precious health care dollars, ” said Margaret O’K. Glavin, FDA’s Associate Commissioner for Regulatory Affairs. “Diabetes requires effective treatments and aggressive management, not bogus and unproven products.”

The joint diabetes initiative to stop commercial sale of fraudulent therapies originated with a Web surf for “hidden traps” by the International Consumer Protection and Enforcement Network (ICPEN), an organization of law enforcement authorities, members of the Mexico, United States, and Canada Health Fraud Working Group (MUCH), and the attorneys general offices of Alaska, Michigan, Ohio, Virginia, and Wisconsin. MUCH, which consists of regulatory officials from health, consumer and competition protection agencies in the three North American countries, had previously conducted a campaign against fraudulent weight-loss products.

Using the results of the Internet sweep, FTC sent warning letters for deceptive ads to 84 domestic and 7 Canadian Web sites targeting U.S. consumers, and referred an additional 21 sites to other foreign governments. About a quarter of the firms have already changed their claims or removed their pages from the Internet, and several others are in contact with FTC.

Today, FDA announced it has issued warning letters to 24 firms marketing dietary supplement products with claims to treat, cure, prevent or mitigate diabetes (see link to Warning Letters at http://www.cfsan.fda.gov/~dms/dialist.html). The FDA letters warn firms that failure to promptly correct the violations may result in enforcement action without further notice, which may include seizure of violative products and/or injunctions against the manufacturers and distributors.

FTC is also announcing today a new consumer education campaign to teach consumers how to avoid phony diabetes cures. The materials encourage consumers to “Be smart, be skeptical!” and will be available in English, Spanish, and French. One component is a “teaser” Web site available at http://wemarket4u.net/glucobate/index.html. At first glance, the site appears to be advertising a cure for diabetes called Glucobate, but when consumers click for more information on ordering the product, it reveals information about avoiding ads for phony cure-alls in the future. The new education materials, including a bookmark and consumer alert, are being introduced in time for Diabetes Awareness Month in November. The American Dietetic Association has agreed to help disseminate the information.

FDA has developed a strategy to focus its enforcement efforts in the area of dietary supplements, and today’s announcement is one important action under that strategy. The strategy was designed to address illegal dietary supplement ingredients and ensure integrity and truthful labeling of dietary supplements. One emphasis is on claims aimed at patients with serious diseases such as cancer and diabetes. Within the last twelve months, the agency has sent more than 100 warning letters and other advisories to Internet firms and has seized products at one firm.

In addition, the agency maintains special Web sites, in English and Spanish, which amplify the agency’s counsel to consumers to check with their doctor, nurse or pharmacist before trying any new health care product. These materials cover a broad range of subjects of special interest to patients with diabetes (see http://www.fda.gov/diabetes/; http://www.fda.gov/diabetes/pills.html;
http://www.fda.gov/opacom/lowlit/diabetes.html; and http://www.fda.gov/opacom/lowlit/sdiabetes.html), as well as more general health care information.

Posted by dlife at 10:55 AM | Comments (0)

Widely Prescribed Diabetes Drug Falls Short of Promise, Says New Review

October 20, 2006 (Newswise) — A new systematic review calls into the question the health benefits versus risks of an oral medicine widely prescribed for diabetes throughout the United States, Canada, Europe and Asia.

The drug — called pioglitazone — is marketed in the United States by Takeda Pharmaceuticals North America, Inc., and Eli Lilly and Co. under the trade name Actos.

“Our results showed that published scientific studies of at least 24 weeks of pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes like mortality, morbidity, adverse effects and health-related quality of life are positively influenced by this drug,” said lead author Bernd Richter, M.D.

“Until new evidence becomes available, the benefit-risk ratio of pioglitazone therapy in type 2 diabetes mellitus remains unclear,” added Richter, assistant professor in the department of endocrinology, diabetes and rheumatology at Heinrich-Heine University in Düsseldorf, Germany.

According to Richter, not only did the review demonstrate no clear-cut benefit to using pioglitazone, but it also showed an increased occurrence of edema and heart failure — including heart failure requiring hospital admission — among patients taking the drug.

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

For the review, the authors analyzed the results of 22 randomized clinical trials involving 6,200 patients with type II diabetes receiving pioglitazone treatment. The longest duration of pioglitazone therapy received by any patient was 34.5 months.

Pioglitazone is one drug in a class of medicines called “thiazolidinediones,” which are said to increase the body’s sensitivity to insulin produced naturally by the body, thereby allowing better uptake of glucose into the cells of the body and lowering blood glucose levels.

Physicians in the U.S. prescribe drugs such as Actos to patients with type II diabetes, whose bodies either do not produce enough natural insulin or don’t use the insulin as effectively as those not affected by diabetes.

HbA1c, or hemoglobin A1c, is a blood test that assesses a patient’s blood glucose levels over time. The HbA1c number correlates with average blood glucose levels during the preceding 120 days, and most tellingly, during the previous eight to 12 weeks.

The review found that pioglitazone lowers HbA1c, but when compared to other active glucose-lowering drugs, similar reductions of HbA1c were achieved, so that “no apparent advantage of pioglitazone treatment could be demonstrated,” said Richter. “Probably, the best comparison would be with metformin, where pioglitazone lowered HbA1c between 1.3 percent and 1.4 percent and metformin by 1.5 percent.”

Pioglitazone has many possible side effects, including fluid retention, weight gain, and leg and ankle “edema” or swelling. In isolated cases it may lead to, or worsen, heart failure.

In the review studies, 15 percent of participants receiving pioglitazone therapy reported edema compared with 7 percent of participants in control groups.

The 15 studies that looked at body weight reported an increase of up to 8.6 pounds in those patients receiving pioglitazone treatment.

In one major study in the review, significantly more patients developed edema and heart failure, including heart failure needing hospital admission, following administration of pioglitazone — 6 percent versus 4 percent on placebo. Heart failure was reported in 11 percent of patients on pioglitazone therapy versus 8 percent on placebo.

The drug may also cause dangerous drops in blood glucose in people taking the drug in combination with insulin or another class of diabetes drugs called “sulfonylureas,” which are marketed in the United States under the generic names glipizide, glyburide, glimepiride and chlorpropamide.

“The kernel from this review is that pioglitazone is effective in glucose-lowering, has some other beneficial and potentially harmful associated features and just has not been evaluated in the right way to prove that it will help people lead longer and more productive lives,” said John Buse, M.D., director of the Diabetes Care Center at the University of North Carolina School of Medicine. “This is true for essentially every drug available for the treatment of diabetes.”

“I am fairly certain that we are better off with pioglitazone than without it,” Buse added. “We do not have proof but a great deal of signal that the benefits outweigh the risks. There are more data to come. The authors of the review are not incorrect in their assessments, but there is just not enough long-term data available in the literature to be certain of the benefits whereas the risks are much easier to assess.”

“Pioglitazone treatment should be restricted to patients demonstrating real benefit of this therapy,” Richter said. “Benefit should not be postulated on the basis of improvement of metabolic parameters like HbA1c reduction alone but should refer to patient-oriented outcomes such as fewer diabetic complications or better health-related quality of life.”

Posted by dlife at 10:41 AM | Comments (3)

Novocell Announces Creation of Insulin-Producing Pancreatic Endocrine Cells

October 19, 2006 (San Diego, CA: PRNewswire)- Novocell, Inc., a stem cell engineering company, today announced the development of a process that efficiently converts human embryonic stem cells into insulin-producing pancreatic endocrine cells. The findings are reported in an article appearing on-line today, in advance of print publication, in the journal Nature Biotechnology. Such an approach could provide a means to produce sufficient quantities of insulin producing cells for transplantation into patients with Type 1 diabetes, a treatment that offers a potential therapy for this disease.

Novocell researchers report in the article a differentiation process that successfully engineers human embryonic stem cells (hESCs) into endocrine cells capable of producing insulin as well as other pancreatic endocrine hormones glucagon, somatostatin, pancreatic polypeptide and ghrelin. The in vitro differentiation process mimics normal pancreatic development in the body.

“The efficient, reproducible production of human embryonic stem cell-derived, insulin-producing endocrine cells through a process that mirrors the development of human pancreatic cells represents a critical step toward providing a renewable source of cells for diabetes therapy,” said Emmanuel Edward Baetge, Ph.D., chief scientific officer of Novocell and senior author of the publication. “This provides a foundation upon which we can build a standardized process for generating functional insulin-producing cells for the treatment of diabetic patients.”

The first step toward generating the insulin-producing cells requires engineering hESCs into definitive endoderm, the gatekeeper cells necessary for formation of the endoderm lineage, including liver, thyroid, parathyroid, lungs, stomach, intestine and pancreas, a process that Novocell reported in Nature Biotechnology in December 2005. From the definitive endoderm, the cells are sequentially matured into foregut endoderm, pancreatic endoderm and endocrine precursors to become pancreatic endocrine cells. The insulin-producing cells contain high levels of insulin similar to levels found in adult human islets. Sugar induced secretion of insulin in the hESC-derived endocrine cells is low, similar to that seen in early human islets. However, these cells are capable of secreting insulin in response to numerous agents, indicating that they have many of the important characteristics of functional beta cells.

Pancreatic islet cells are destroyed in patients with diabetes, and these patients require regular insulin treatment. The transplantation of donor-derived human islets, combined with chronic immunosuppression, has been demonstrated to be an effective therapy for the treatment of diabetes. However, the limited availability of donated pancreatic islets and the adverse side effects of long-term immunosuppression make this type of replacement therapy unsuitable for the general diabetic population, thus limiting its utility.

In addition to generating sufficient amounts of insulin-producing cells from hESCs, Novocell has developed a process by which such cells could potentially be delivered to patients without the need for chronic immunosuppression. The Company’s cell encapsulation technology provides a protective, biocompatible coating for cells that shields them from the immune system, thus allowing them to be more readily accepted in the body without the chronic use of immunosuppressive drugs. Novocell is currently conducting human clinical trials examining the safety and efficacy of subcutaneous implants of encapsulated human primary islet allografts in patients with Type 1 diabetes of long standing duration.

“We anticipate that the combination of our stem cell-generated insulin producing cells with our cell encapsulation technology will provide a treatment option eliminating the two principal barriers precluding widespread application of cell replacement therapies – a limited cell source and immunosuppression,“ said Alan J. Lewis, Ph.D., president and chief executive officer of Novocell. “Such an approach could truly transform diabetes treatment and greatly reduce medical costs associated with current insulin administration as well as the number of additional drug treatments used to reduce side effects associated with this devastating disease.“

Posted by dlife at 11:31 AM | Comments (1)

Global Online Petition Demands UN Resolution on Diabetes

Diabetes activists seek action to halt epidemic.

Brussels, Belgium, October 18, 2006 - The ‘Unite for Diabetes’ campaign, led by the International Diabetes Federation, has launched an online petition to rally global support for a United Nations Resolution on diabetes at http://www.unitefordiabetes.org. Diabetes is now one of the world’s most significant causes of healthcare expenditure, mortality, disability and lost economic growth. ‘Unite for Diabetes’ is a campaign to raise awareness of diabetes and the need for a Resolution to tackle the disease.

The support of a majority of the member states will be required to pass a United Nations Resolution on diabetes. The global petition is a way to engage diabetes activists worldwide to alert their national governments to the serious nature of diabetes and encourage support for a UN Resolution to help tackle the epidemic.

President-Elect of the International Diabetes Federation Professor Martin Silink leads the campaign. He urged people to sign the online petition and pass the diabetes pin in the name of all those living with diabetes. “Together we can slow down the advance of diabetes and even reverse the current trends. A United Nations Resolution on diabetes will help bring this silent killer out of the shadows.”

About the campaign
The People’s Republic of Bangladesh is the lead sponsor for the Resolution on diabetes. The Resolution encourages UN Member States to develop national policies for the treatment, care and prevention of diabetes within the sustainable development of their healthcare systems and asks for a UN-observed World Diabetes Day on 14 November starting in 2007. The ‘Unite for Diabetes’ campaign asks all nations to support the People’s Republic of Bangladesh and vote in favour of a UN Resolution on diabetes.

The campaign encourages everyone to show support for the Resolution by signing a global petition and by forwarding a virtual diabetes pin to friends and family, and in turn inviting them to show the same support. The diabetes pin takes the form of a blue circle in the colour of the UN flag. It is the logo for the ‘Unite for Diabetes’ campaign and is a tribute to the millions of people living with diabetes worldwide.

About diabetes
Diabetes is devastating communities around the world. More than 230 million people now live with a disease that kills over 3.5 million people each year. Despite the growing numbers and threat to life, many remain ignorant. Each year 7 million people get diabetes, joining the more than 230 million people now living with the disease. Diabetes kills more people each year than HIV/AIDS and impacts all nations, rich and poor.

Bangladesh is expected to be among the top 10 countries with the largest number of people with diabetes. Today 3.8 million people live with diabetes in the country. This is expected to rise to 7.4 million by 2025. Bangladesh is not the only country to face such an overwhelming increase in the number of people with diabetes. The disease is expected to affect more than 350 million people globally within the next two decades if nothing is done.

The world needs a UN Resolution on diabetes. While the problem is global, its full dimension and impact remain unrecognized, particularly in the world’s low- and middle-income nations. For these countries, cheap life-saving treatments are available and would be easy to distribute, but are rarely used. At the same time, much can be done to prevent diabetes in those at risk. The unified voice of the whole United Nations is needed to impress these facts upon the world.

“Diabetes is an enormous problem with devastating consequences worldwide. It likely affects someone you know and love. It is a leading cause of blindness, amputation, heart attack, stroke and often a premature death. Yet it is too often dismissed as something trivial: a touch of sugar. Diabetes is not trivial; there is no such thing as mild diabetes.” said Professor Silink. “We owe it to future generations to spare them from the severe humanitarian, social and economic burden of diabetes.”

Posted by dlife at 08:34 AM | Comments (1)

FDA Approves Januvia for Type 2 Diabetes

October 17, 2006 (FDA) - The Food and Drug Administration (FDA) announced today the approval of Januvia (sitagliptin phosphate) Tablets, the first diabetes treatment approved in a new class of drugs known as DDP-4 inhibitors that enhances the body's own ability to lower elevated blood sugar.

FDA approved Januvia for use in addition to diet and exercise to improve blood sugar levels in patients with type 2 diabetes, alone or in combination with two other commonly prescribed oral diabetes medications, metformin or a PPAR (peroxisome proliferator-activated receptor gamma) agonist, when either of these drugs alone, along with diet and exercise, don't provide adequate blood sugar control.

"For the millions of Americans with type 2 diabetes, who continue to have inadequate blood sugar control, the approval of Januvia marks an important advance in the fight against diabetes," said Dr. Steven Galson, Director of FDA's Center for Drug Evaluation and Research. "We now have another new option that treats the disease in an entirely new way that can be added to existing treatment regimens to help patients gain more control over their blood sugar levels."

Type 2 diabetes is the most common form of the disease, accounting for about 90 percent to 95 percent of all diagnosed cases of diabetes (20.8 million in 2005). In type 2 diabetes, the body does not produce enough insulin or the cells ignore the insulin. Insulin is necessary to take sugar, the basic fuel for cells, from the blood into the cells. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, nerve damage, and kidney damage.

Januvia prolongs the activity of proteins that increase the release of insulin after blood sugar rises, such as after a meal. Januvia does this by blocking an enzyme (dipeptidyl peptidase IV or DPP-IV) which breaks down these proteins, leading to better blood sugar control.

Januvia was examined in a total of 2,719 patients with type 2 diabetes, in studies lasting from 12 weeks to more than a year. These studies demonstrated improved blood sugar control when Januvia was used alone or in patients not satisfactorily managed with metformin or a PPAR agonist.

The most common side effects in clinical studies were upper respiratory tract infection, sore throat, and diarrhea.

Posted by dlife at 10:59 AM | Comments (139)

FDA Issues Nationwide Alert on Counterfeit One Touch Basic/Profile and One Touch Ultra Blood Glucose Test Strips

October 13, 2006 (FDA) - The U.S. Food and Drug Administration (FDA) is alerting the public to counterfeit blood glucose test strips being sold in the United States for use with various models of LifeScan, Inc., One Touch Brand Blood Glucose Monitors used by people with diabetes to measure their blood glucose.

The counterfeit test strips potentially could give incorrect blood glucose values--either too high or too low--which might result in a patient taking either too much or too little insulin and lead to serious injury or death. No injuries have been reported to FDA to date.

The counterfeit test strips are:

One Touch Basic®/Profile® (lot #272894A, 2619932 or 2606340) test strips; and,
One Touch Ultra® (lot #2691191) test strips.
Consumers who have the counterfeit test strips should stop using them, replace them immediately and contact their physician. Consumers with questions may contact the company at 1-866-621-4855.

The counterfeit test strips were distributed to pharmacies and stores nationwide--but primarily in Ohio, New York, Florida, Maryland and Missouri--by Medical Plastic Devices, Inc., Quebec, Canada and Champion Sales, Inc., Brooklyn, N.Y.

The counterfeit test strips can be identified by the following characteristics:

Counterfeit One Touch Basic/Profile Test Strips

Lot Numbers 272894A, 2619932 or 2606340
Multiple Languages- English, Greek and Portuguese text on the outer carton
Limited to 50-Count One Touch (Basic/Profile) Test Strip packages
Counterfeit One Touch Ultra Test Strips

Lot Number 2691191
Multiple Languages- English and French text on the outer carton
Limited to 50-Count One Touch Ultra Test Strip packages
LifeScan alerted FDA of the counterfeit test strips. The agency is investigating the matter.

LifeScan is alerting the public via a press release and is notifying pharmacists, distributors, and wholesalers through a letter. In its letter, the company is advising customers to contact their original source of supply for restitution. For more information, visit: www.GenuineOneTouch.com.

FDA is alerting its Counterfeit Alert Network partners, a coalition of healthcare professional, consumer and trade associations, who have agreed to further disseminate this important information in a timely and effective manner.

Any adverse reactions 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 through the MedWatch Web site at www.fda.gov/medwatch.

Posted by dlife at 08:38 PM | Comments (0)

Plan Will Guide NIH Research In Type 1 Diabetes

October 13, 2006 (NIH) - The National Institutes of Health (NIH) has released a long range plan that will help to guide research in type 1 diabetes for the next decade. "Advances and Emerging Opportunities in type 1 Diabetes Research: A Strategic Plan” identifies goals and objectives to exploit recent scientific advances in combating this autoimmune form of diabetes.

About 5 to 10 percent of the nearly 21 million people with diabetes have type 1, formerly known as juvenile onset diabetes or insulin-dependent diabetes. In this form of diabetes, immune cells attack and destroy pancreatic beta cells, which produce the critical hormone insulin needed for survival. Type 1 diabetes tends to arise in children and young adults, who need three or more insulin injections a day or treatment with an insulin pump to maintain blood glucose control. To prevent complications they must regularly monitor their blood glucose, striving for a range that is as close to normal as possible. The constant challenge of managing the disease poses a serious burden for patients and their families.

Type 1 diabetes cuts lives short by about 15 years, with early deaths due mainly to heart attacks and strokes. However, research has made dramatic progress in extending life expectancy for people with this disease. A recent study found that 20 percent of people born in the 1950's died within 20 years of a type 1 diabetes diagnosis, and 30 percent died within 25 years of diagnosis. For people born between 1975 and 1980, however, 3.5 percent died within 20 years of diagnosis, and 7 percent died within 25 years.

"Research has greatly improved the length and quality of life of people with type 1 diabetes, and it has lowered the risk of developing certain serious complications, such as retinopathy and kidney failure. However, many challenges remain in combating this complex autoimmune disease.

The NIH Strategic Plan sets forth a cogent, multifaceted approach to future research that soundly addresses these challenges," said NIH Director Elias A. Zerhouni, M.D.

The Plan describes scientific advances resulting from type 1 diabetes research and outlines specific objectives to further the following
goals:

1. IDENTIFY THE GENETIC AND ENVIRONMENTAL CAUSES OF TYPE 1 DIABETES
Both genetic susceptibility and one or more environmental triggers contribute to the development of type 1 diabetes. Genes that confer varying degrees of risk have been identified, but researchers continue to search for others. Finding all the genes will boost the ability to predict who is at risk and foster prevention efforts. Because many people with high-risk genes don't develop type 1 diabetes, scientists believe environmental factors -- perhaps toxins, infectious agents, or components of the diet -- also play a role. Several groups, including the International Type 1 Diabetes Genetics Consortium and The Environmental Determinants of Diabetes in the Young (TEDDY), are working to identify all the genetic and environmental factors that lead to diabetes. The outcome of their work could have enormous benefits, such as a preventive vaccine against an infectious trigger or a dietary change that averts autoimmunity and diabetes onset.

2. PREVENT OR REVERSE TYPE 1 DIABETES
Researchers have made great strides in understanding, detecting, and monitoring autoimmunity and now have better tools to study the early stages of type 1 diabetes. Testing for genetic susceptibility and autoantibodies, they can identify who is at high, moderate, and low risk for developing type 1 diabetes. They also have a better grasp of the immune events that lead to the destruction of beta cells. Several studies now point to insulin itself as the target of immune cells.

Clinical trial groups, including the Type 1 Diabetes TrialNet and the Immune Tolerance Network, are currently testing ways to modulate the immune system to prevent type 1 diabetes and to arrest the autoimmune attack in people with newly diagnosed diabetes, who still have some functioning beta cells.

3. DEVELOP CELL REPLACEMENT THERAPY
Since 2000, when researchers at the University of Alberta in Edmonton, Canada, pioneered a new method for transplanting islets, or clusters of beta cells, researchers have been steadily refining the procedure for people with severe complications from type 1 diabetes. Islet transplantation improves glucose control and alleviates hypoglycemia unawareness, which afflicts some people with longstanding type 1 diabetes. However, the side effects of immunosuppressive drugs, which prevent the body's rejection of donor islets, have limited the procedure to people with hypoglycemia unawareness or those already taking immunosuppressive drugs after a kidney transplant. Researchers seek to overcome the remaining barriers to islet transplantation by:

• Developing methods to produce an unlimited supply of islets
• Improving ways to harvest islets
• Reducing complications of islet transplantation, and
• Testing ways to prevent recurrent autoimmunity and the immune rejection of donor islets.

To address the inadequate supply of donor islets, the Beta Cell Biology Consortium is exploring beta cell development and regeneration with the goal of growing unlimited numbers of beta cells. Other projects include a registry that tracks the outcomes of islet transplants and a research group that is testing ways to induce immune tolerance in non-human primate models of kidney and islet transplantation.

4. PREVENT OR REDUCE HYPOGLYCEMIA IN TYPE 1 DIABETES
Major clinical studies have clearly shown that intensive glucose control dramatically delays or prevents the eye, nerve, kidney, and heart complications of type 1 diabetes. The main barrier to tight control is hypoglycemia, which occurs when insulin causes blood glucose to fall too low. Some patients with difficult-to-control diabetes cannot sense falling blood glucose and lose consciousness without warning. Recently approved continuous glucose monitors developed with NIH support are helping patients control their glucose levels more easily. This revolutionary technology is the first step in the path to develop an artificial pancreas. Current studies are also focusing on how the brain senses hypoglycemia and controlling hypoglycemia through behavioral therapy.

5. PREVENT OR REDUCE THE COMPLICATIONS OF TYPE 1 DIABETES
Together, diabetes and high blood pressure account for 72 percent of all new cases of kidney failure. After 20 years of annual increases from 5 to 10 percent, rates for new kidney failure cases have leveled off. The most encouraging trend is in diabetes, where rates for new cases in whites under age 40 are the lowest in 20 years. Improved control of glucose and blood pressure and the use of anti-hypertensive drugs called ACE inhibitors and ARBs prevent or delay kidney failure. With good care, fewer than 10 percent of people with diabetes now develop kidney failure.

Scientists have made great progress in preventing and treating the eye damage of diabetes. With laser treatment and vitrectomy, blindness has been reduced by 90 percent in patients with severe diabetic retinopathy.

NIH researchers discovered that a protein called vascular endothelial growth factor (VEGF) spurs the development of abnormal blood vessels that invade the retina to cause blindness. NIH-sponsored clinical studies are now testing drugs that control the development of new blood vessel growth in the eye.

Advances in understanding how high blood glucose causes damage to cells and tissues have led to several promising drugs that are ready for testing in clinical trials to treat and prevent complications. The Strategic Plan stresses the need to further clarify these pathways by studying the role of genetic factors and applying the tools of systems biology.

6. ATTRACT NEW TALENT AND APPLY NEW TECHNOLOGIES TO RESEARCH ON TYPE 1 DIABETES
Engaging talented scientists from diverse disciplines is critical to the success and future of diabetes research. The NIH is vigorously pursuing this goal in different ways, e.g., by encouraging interdisciplinary collaboration, creating incentives that reward research innovation and collaboration, and attracting and training new diabetes investigators.

By employing powerful new technologies, researchers are poised to solve the most vexing problems of type 1 diabetes research. It is well known, for example, that patients have already lost most of their beta cells by the time type 1 diabetes is diagnosed. Having a way to measure the actual number of beta cells would greatly help researchers in their quest to develop new therapies. State-of-the-art diagnostic tools, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are giving hope that beta cell mass can be assessed in real time to judge the effects of promising therapies. Imaging technologies are also being applied to better understand the brain's response to hypoglycemia.

Posted by dlife at 04:16 PM | Comments (0)

Structure of Enzyme Offers Treatment Clues for Diabetes, Alzheimer's

October 11, 2006 (EurekAlert) - Researchers from the University of Chicago and Argonne National Laboratory have deciphered the three-dimensional structure of insulin-degrading enzyme, a promising target for new drugs because it breaks down not only insulin but also the amyloid-beta protein, which has been linked to the cognitive decline of Alzheimer's disease.

In the October 19, 2006, issue of Nature (available online Oct. 11), the researchers describe the structures of insulin-degrading enzyme (IDE) in complex with four of the proteins it digests: insulin, amyloid-beta, amylin and glucagon. The structures are exciting because they suggest ways to develop drugs that could either speed up or slow down this ubiquitous enzyme's activity.

"The structure of insulin-degrading enzyme tells us a lot about how it works, which is somewhat unorthodox," said Wei-Jen Tang, Ph.D., associate professor in the Ben May Institute for Cancer Research at the University of Chicago and director of the study. "Understanding how it works gives us clues about how to design drugs either to inhibit or activate it."

"By introducing small, targeted mutations, we have already been able to increase the enzyme's activity by as much as 40-fold," he said. "That gives us a blueprint for the next step, trying to devise a drug that would produce a similar effect."

Ever since I. Arthur Mirsky discovered IDE in 1949, physicians have sought ways to manipulate it. Mirsky thought that by inhibiting the enzyme he could help diabetics by making their insulin remain active longer. More recently, as scientists realized that IDE was also involved in clearance of amyloid-beta, they have begun searching for ways to supercharge the enzyme to see if it could prevent the build-up of the amyloid plaques that are a hallmark of Alzheimer's disease.

Despite more than half a century of intensive research, however, insulin-degrading enzyme has remained "an especially elusive pharmacological target," biochemist Malcolm Leissring of the Scripps Research Institute and neurobiologist Dennis Selkoe of Harvard Medical School wrote in a commentary that accompanies the Nature article.

Using the Advanced Photon Source at Argonne National Laboratory, Tang and colleagues were able to solve the structures of this enzyme in complex with insulin and with amyoid-beta, as well as amylin and glucagon. These "high-resolution crystal structures open the door to the rational design of pharmacological modulators of this important protease," wrote Leissring and Selkoe.

The enzyme, Tang's team reports, resembles the video-game character "Pac-Man," with two bowl-shaped halves joined by a hinge at one end and held closed, most of the time, by a latch of hydrogen bonds on the other end. When the bowls come together, like a shut mouth, they enclose a chamber, shaped like a triangular prism, with a base that measures 35 x 34 x 30 angstroms and a height of 36 angstroms, large enough to contain relatively small peptides, such as insulin or amyloid-beta, which have fewer than 50 amino acids.

Although it can cleave larger molecules, the proteins IDE degrades most readily fit neatly within this chamber. Negative electrical charges on their outer surfaces help to align them with the positive charges on one inner surface of the chamber. Once they are in place, the enzyme slices them multiple times into tiny pieces, which are then discarded.

Although the enzyme's structure is similar to Pac-Man, its behavior differs. Pac-Man keeps his mouth wide open to gobble up anything in his path. With IDE the mouth is usually closed. The hydrogen-bond latch that holds the jaws together protects its active, or catalytic site.

But in a series of experiments, Tang and colleagues were able to make small mutations of IDE that altered only the latch, disrupting the alignment of contacts that normally keep the enzyme closed. Three of these altered versions of wide-open IDE proved to be 30 to 40 times more active than the normal version of the enzyme.

"This suggests that the rate-limiting step may be the speed at which the enzyme can reopen and then clamp down on a new morsel rather than the time it takes to chew something up," said Tang. "This makes us think that if we can slightly alter its shape, we can substantially boost its activity."

The researchers are now searching for small molecules that can duplicate the effects of those mutations, shifting the balance toward the open rather than the closed state. "Such compounds," the authors note, "might facilitate the clearance of amyloid-beta and other pathologically relevant IDE substrates."

Posted by dlife at 04:13 PM | Comments (0)

Dental Infection Linked to Diabetes During Pregnancy

October 10, 200 (Newswise) — Nearly one out of two women with gestational diabetes also have periodontal disease, according to research released this month by Tulane University researchers. In contrast, just over one in ten pregnant women without gestational diabetes have periodontal disease. The study, available in the October issue of the American Journal of Obstetrics and Gynecology, is the first to demonstrate a link between poor oral health and diabetes during pregnancy.

Periodontal disease is a chronic infection of the gums and mouth. Gestational diabetes is an inability to process dietary sugars normally during pregnancy. Gestational diabetes puts women and their babies at increased risk of injury and illness.

The team of researchers analyzed health data from 256 pregnant women who participated in the National Health and Nutrition Examination Study III. Based on their analysis, the researchers recommend that dental care during pregnancy should be considered as a way to help prevent gestational diabetes.

Study authors are Tulane obstetrician Gabriella Pridjian; Tulane epidemiologists Xiong Xu and Pierre Buekens; and Louisiana State University dental health researcher Sotirios Vastardis.

Posted by dlife at 05:31 PM | Comments (0)

New Evidence Finds an Association Between Periodontal Disease and Stroke

Researchers from Boston University investigate the relationship between periodontal disease and ischemic stroke

CHICAGO, October 10, 2006 (Eurekalert) -- People missing some or all of their teeth or who have significant loss of bone and tissue surrounding their teeth may be at an increased risk for having a stroke, according to a new study that appeared in the October issue of the Journal of Periodontology (JOP).

Researchers from Boston University investigated the relationship between periodontal disease and history of stroke in patients 60 years of age and older by examining the data of the Third National Health and Nutrition Examination Survey (NHANES III).

"We found that patients 60 years and older who were edentulous, partially edentulous and/or had significant clinical attachment loss were more likely to have a history of stroke compared to dentate adults without significant clinical attachment loss," said Dr. Martha E. Nunn, Goldman School of Dental Medicine, Boston University. "However, based on the results of this study, it is unclear whether periodontal disease is an independent risk factor for stroke or simply a risk marker that reflects negative effects of risk factors common to both periodontal disease and stroke."

Age, tobacco use, hypertension, diabetes, serum glucose, C-Reactive protein (CRP) and alcohol intake were also included as additional risk factors in this study. These confounders are independent risk factors for cardiovascular disease and if left untreated, periodontitis has been shown to have harmful effects on the control of diabetes, serum glucose levels and increases CRP levels.

Evidence continues to accumulate associating severe periodontitis with an increased risk of forming atherosclerotic plaques, which are responsible for myocardial infarction and ischemic stroke. According to past JOP studies, this relationship could be due to elevated CRP levels in patients with chronic periodontal disease.

Further investigation is needed to support periodontal treatment intervention as a means of controlling systemic inflammation. Based on findings from another study in this JOP issue, CRP levels may now be reduced by periodontal treatment such as scaling and root planing in patients with severe periodontal disease.

"Studies evaluating additional treatment methods such as repeated scaling and root planing or surgical treatment are needed to conclusively demonstrate that CRP can be improved by periodontal treatment," said Preston D. Miller, DDS and AAP president. "Until science presents a definitive direction, the periodontists ultimate goal is to lead patients to the right side of health. What we do know is that eliminating periodontal infection saves teeth."

Posted by dlife at 03:59 PM | Comments (0)

U.S. Regulatory Authority Lifts Import Alert for Accu-Chek Spirit Insulin Pump System

October 9, 2006 (Roche) - Roche today announced that the US Food and Drug Administration (FDA) has lifted the import alert for the sale of Accu-Chek insulin pumps by Disetronic Medical Systems AG (Burgdorf, Switzerland) for customers in the United States, following the inspection of the Disetronic site last year.

“This is an important milestone for our Diabetes Care business unit and for all our employees who contributed to the achievement. It confirms our ongoing commitment to quality, regulatory and compliance programs across the world. In addition, we appreciate the support from the agency throughout the assessment process” said Severin Schwan, CEO Division Roche Diagnostics and Member of Roche’s Corporate Executive Committee.

The lift of the import alert clears the path for an imminent launch of the Accu-Chek Spirit insulin pump system in the U.S. The insulin pump has been well received by consumers and healthcare professionals around the world. Currently, the Accu-Chek Spirit insulin pump is available in more than 30 countries. The FDA announcement is a further step toward worldwide access to the full insulin delivery portfolio of Roche.

Posted by dlife at 09:36 AM | Comments (0)

Pine Tree Bark Reduces Diabetic Microangiopathy

Study reveals 68 percent improvement of blood flow

October 4, 2006 (EurekAlert) - Diabetic microangiopathy is responsible for major diabetic health complications, such as leg ulcers, kidney failure and retinopathy. It is imperative diabetics receive the best treatment to manage this condition. A study published in the September edition of Angiology shows that Pycnogenol (pic-noj-en-all), an antioxidant plant extract from the bark of the French Maritime pine tree, significantly reduced diabetic microangiopathy (DM) in patients after supplementing with Pycnogenol.

"Diabetic microangiopathy is not a rare phenomenon and essentially affects every diabetic person. The condition may result in vision loss in diabetic retinopathy, kidney problems and ischemic tissue necrosis causing leg ulcers which may lead to amputation," said Dr. Gianni Belcaro, a lead researcher of the study. "With DM, the walls of very small blood vessels (capillaries) become so weak, bleeding and protein leaks occur, which ultimately slows down blood flow, resulting in blood clots and swelling of the limbs (edema)."

The study sampled 60 diabetic patients suffering from DM being treated with insulin for at least three years at the Chieti-Pescara University in Italy. In addition to their insulin treatment, patients received 150 mg of Pycnogenol orally daily for one month. The control group, 50 percent of the sample, received a placebo. Measurements of blood flow were measured by laser Doppler.

Measurements were taken when patients were lying down and standing up. The capillary adaptation to increased pressure from lying down to standing is generally impaired, due to vessel failure and increase of pressure in capillaries for individuals who suffer from DM.

Results showed that when patients were lying down, Pycnogenol treatment improved capillary blood flow by 34 percent, compared to 4.7 percent in the placebo group. When patient's blood flow was measured in a standing position, Pycnogenol treatment improved capillary blood flow by 68 percent, compared to 8 percent in the placebo group.

Capillary leakage was recorded by measuring ankle swelling, which develops ten minutes after passing from lying down to standing up. After Pycnogenol treatment, swelling was 17 percent lower, compared to 2.6 percent in the placebo group.

"The rapid improvement of microvessel complication with Pycnogenol in just four weeks is clinically remarkable," said Dr. Belcaro, who has been a large part of previous Pycnogenol and diabetes related studies.

In July, a study was published supporting diabetic foot ulcer treatment with Pycnogenol. Results revealed almost 75 percent decrease in ulcer size in patients who supplemented with both oral and local Pycnogenol. Previous research supports Pycnogenol treatment to be highly effective for prevention of diabetic retinopathy and to be effective in lowering glucose levels and increasing the health of blood vessels in patients with type II diabetes. Previous research may be found at www.pycnogenol.com.

Posted by dlife at 11:23 AM | Comments (1)

One-Third of U.S. Youth Not Physically Fit

October 3, 2006 CHICAGO - Approximately one-third of boys and girls age 12 to 19 in the United States do not meet standards for physical fitness, according to a report in the October issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

The more physically fit a young person, the less likely he or she is to have high blood pressure, high cholesterol levels or a number of other risk factors for chronic diseases, according to background information in the article. Between the 1950s and the 1980s, regular surveys of youth physical fitness were conducted in the United States. An increasing proportion of children have become obese since the 1980s, which may be explained by a decrease in physical activity. If so, it is likely that average physical fitness has also declined among youth in the same time period, since the last national survey.

Russell R. Pate, Ph.D., Arnold School of Public Health, University of South Carolina, Columbia, and colleagues assessed the physical fitness of 3,287 individuals age 12 to 19 who participated in the government-conducted National Health and Nutrition Examination Survey between 1999 and 2002. The participants were interviewed in their home and then visited a mobile examination center, where they performed a treadmill exercise test consisting of a two-minute warm-up, two three-minute periods of exercise and a two-minute cool-down. During the test, researchers measured blood pressure, heart rate and rate of perceived exertion, determined by asking participants to rate how hard they feel their bodies are working. Heart rate readings during the three-minute periods of exercise were used to estimate maximal oxygen uptake (VO2max), the amount of oxygen consumed by the body during maximum exertion; the higher the VO2max, the better the individual's fitness level.

Estimated VO2max, and therefore physical fitness levels, were higher on average in males than in females and in youth of normal weight compared with overweight youth but were no different across racial or ethnic groups. Older males were more physically fit than younger males, while the opposite was true for females. Participants who reported more sedentary behavior, such as watching television or playing video games, and those who spent less time being physically active were more likely not to be physically fit.

Based on standards developed by experts and used by schools and school districts nationally, about 65 percent of youth met criteria for being physically fit. "This represents a significant public health problem because low physical fitness during adolescence tends to track into adulthood, and low-fit adults are at substantially increased risk for chronic disease morbidity [illness] and mortality [death]," the authors write. Because active youth tend to be more physically fit, experts recommend that physicians counsel children and parents about guidelines for physical activity, they conclude.

Posted by dlife at 11:35 AM | Comments (0)

One in 523 Children and Adolescents Have Diabetes

October 2, 2006 (Newswise) — About one in every 523 children and adolescents in the United States had physician-diagnosed diabetes in 2001, according to estimates from a major national study called SEARCH for Diabetes in Youth.

SEARCH is the largest surveillance effort of diabetes among youth under the age of 20 ever conducted in the United States, said Ronny A. Bell, Ph.D., M.S., associate professor of epidemiology and prevention at Wake Forest University School of Medicine and a SEARCH co-investigator. It is the first look at the burden of diabetes in youth of all major racial and ethnic groups.

In a report in the October issue of Pediatrics, study investigators estimate that about 154,000 of roughly 80.7 million children and adolescents nationwide had diabetes in 2001. The number of youth with diabetes varies across major U.S. racial and ethnic groups and across age groups.

In children up through 9 years of age, non-Hispanic white children had the highest diabetes rate (about 1 in every 1,000 children). In this age group across all racial and ethnic groups, physician-diagnosed type 1diabetes, previously known as insulin-dependent diabetes, was the most common form of diabetes. The study found that type 2 diabetes was extremely rare in children under 10 years of age of all races.

Among adolescents and young adults, black and non-Hispanic white youth had the highest overall burden of diabetes (about 1 in every 315) and Asian/Pacific Islander had the lowest (about 1 in 746). Type 1diabetes was the most common form of diabetes in all racial/ethnic groups except in American Indian youth.

Type 2 diabetes was found in all racial and ethnic groups in youth 10 to 19. It represented only 6 percent of the cases of diabetes in non-Hispanic whites, 33 percent in blacks, and 40 percent in Asian/Pacific Islanders, but was the most common form of diabetes, at 76 percent, among American Indian youth.

“The study was funded precisely because there was such a lack of systematically collected population-based prevalence data, especially for Type 2 diabetes,” said Angela D. Liese, Ph.D., M.P.H., of the University of South Carolina in Columbia, the lead author.

“This important study has been extremely challenging due to the great difficulty of accurately finding all the cases of diabetes in this age group,” said Michael Engelgau, M.D., acting director of the Division of Diabetes Translation at the Centers for Disease Control and Prevention. “However, the effort is well worth it. This information will be critical to understanding this disease in children, which will lead to actions to better control it and to minimize its effects on our younger generation,” he said.

“This study addresses an important gap in our knowledge, providing national estimates on the prevalence of type 1 and type 2 diabetes in children,” said Judith Fradkin, M.D., director, Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK.)
Liese said that study investigators would continue to track the incidence of diabetes cases in all of the various population groups over the next few years.

“Increasing obesity in children began in the late 1980s or early 1990s, and people have speculated that the increase in obesity is associated with an increased risk of type 2 diabetes in youth,” Liese said.

The study investigators write, “Diabetes is one of the leading chronic diseases in childhood and adolescence.” The prevalence of 1.82 per thousand is higher, for instance, than the rate of 1.24 per thousand for cancer, but lower than asthma (120 per thousand).

“Diabetes affects quality of life severely for these youth, has a major impact on their families, and has a significant public health impact,” the investigators say in the report. “Persons diagnosed with diabetes before 20 years of age have a markedly lower life expectancy than the general population without diabetes.”

Posted by dlife at 11:31 AM | Comments (0)