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Archive - 04 - 2012

Scientists Awarded $2.4 Million to Study Genetic Variation in People with Diabetes

Posted by dlife on Mon, Apr 30, 12, 01:54 PM 0 Comment

April 30, 2012 (Newswise) A UNC-led team of scientists has received a $2.4 million grant to study genetic variations in people with diabetes.The goal of the study is to identify genetic variations that may help predict the response to various treatment options for type 2 diabetes to reduce cardiovascular disease, said Dr. John Buse, co-principal investigator and director of the Diabetes Care Center at the University of North Carolina at Chapel Hill.We hope this work will enable us to target interventions to patients most likely to benefit and least likely to be harmed, Buse said.The genes containing these variants may also prove to be novel targets for drug development, leading to new medicines for improving outcomes for diabetic patients in the future.The 4-year grant was awarded by National Heart, Lung and Blood Institute of the National Institutes of Health (Award Number R01HL110380). This project is one of several in the area of pharmacogenomics and personalized medicine supported by the North Carolina Translational and Clinical Sciences (NC TraCS) Institute, the academic home of NIHs Clinical and Translational Science Award (CTSA) at UNC. The CTSA program aims to improve human health by transforming the research and training environment to enhance the efficiency and quality of clinical and translational research.Michael Wagner, PhD, research professor in the UNC Eshelman School of Pharmacy is co-principal investigator of the study. Co-investigators are Howard McLeod, PharmD, Fred Eshelman Distinguished Professor of Pharmacogenomics and Individualized Therapy and director of the UNC Institute for Pharmacogenomics and Individualized Therapy (IPIT), and Alison Motsinger-Reif, PhD, assistant professor of statistics at North Carolina State University and adjunct professor in the UNC IPIT.This study is a follow-up to the ACCORD trial, which found no additional improvement in cardiovascular events in patients treated with intensive diabetes, blood pressure or lipid therapy.These failures of seemingly rational treatment approaches could be the result of differential response due to genetic variation, Wagner said. Our study is aimed at identifying the genetic variations that may be involved.

Two Drugs Better Than One to Treat Youth With Type 2 Diabetes

Posted by dlife on Mon, Apr 30, 12, 11:47 AM 0 Comment

April 29, 2012 (National Institutes for Health) NIH-funded study addresses emerging health problem.A combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone, a study funded by the National Institutes of Health (NIH) has found. Adding an intensive lifestyle intervention to metformin provided no more benefit than metformin therapy alone.The study also found that metformin therapy alone was not an effective treatment for many of these youth. In fact, metformin had a much higher failure rate in study participants than has been reported in studies of adults treated with metformin alone.The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study is the first major comparative effectiveness trial for the treatment of type 2 diabetes in young people. TODAY was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH. Study results will appear in the New England Journal of Medicine on April 29, 2012, atwww.nejm.org/doi/full/10.1056/NEJMoa1109333.The results of this study tell us it might be good to start with a more aggressive drug treatment approach in youth with type 2 diabetes,said Philip Zeitler, M.D., Ph.D., the TODAY study chair and a pediatric endocrinologist at Children's Hospital Colorado, Aurora.We are learning that type 2 diabetes is a more aggressive disease in youth than in adults and progresses more rapidly, which could be why metformin alone had a higher than expected failure rate.The TODAY study tested how well and for how long each of three treatment approaches controlled blood glucose levels in youth enrolled from ages 10 to 17 with type 2 diabetes. Participants were randomly assigned to one of three treatment groups: metformin alone, metformin and rosiglitazone together, and metformin plus intensive lifestyle changes aimed at helping participants lose weight and increase physical activity.The study found that treatment with metformin alone was inadequate for maintaining acceptable, long-term, blood glucose control in 51.7 percent of youth over an average follow-up of 46 months. The failure rate was 38.6 percent in the metformin and rosiglitazone group, a 25.3 percent reduction from metformin alone. In the metformin plus lifestyle group the failure rate was 46.6 percent.The childhood obesity epidemic has led to the emergence of type 2 diabetes in youth. However, because type 2 diabetes has been primarily an adult illness, information about how to effectively treat youth is limited, and pediatric diabetes experts have had to rely on what is known about adult treatment.Currently, metformin is the standard treatment for young people with type 2 diabetes and the only oral drug approved for this use by the U.S. Food and Drug Administration.The longer a person has type 2 diabetes, the greater the likelihood of developing complications including coronary artery disease, stroke, kidney and eye disease, and nerve damage, making it critical for young people with type 2 diabetes to quickly achieve and sustain control of their blood glucose.This important study provides much-needed information about how to treat type 2 diabetes in young people. Earlier studies in adults have shown that early, effective treatment can prevent serious and costly diabetes complications later in life, said NIDDK Director Griffin P. Rodgers, M.D. Longer-term follow up will be important to understand whether more aggressive therapy for youth with type 2 diabetes will yield long-term benefits as they move into adulthood.In September 2010, the FDA restricted the use of rosiglitazone because of studies linking the medicine to a higher risk of heart attacks and stroke in adults. The TODAY Data Safety and Monitoring Boardan independent group of health and science expertscarefully examined all safety data for TODAY participants and recommended that the study should continue to test rosiglitazone. Rosiglitazone is sold commercially as Avandia.Studies have shown lifestyle-change programs to be effective in improving blood glucose control for adults with type 2 diabetes. However, the TODAY lifestyle interventiona family-based weight-management program that included intensive education and activities delivered one-on-one by trained study staffadded no benefit to the metformin therapy. Some youth lost weight during the study, but the majority did not.Despite a rigorous lifestyle intervention, we were unable to achieve sustained lifestyle changes in these youth, though similar strategies have proven effective in adults, said Barbara Linder, M.D., Ph.D., NIDDK senior advisor for childhood diabetes research. TODAY investigators will look more closely at those youth who succeeded in losing weight to better understand how to achieve effective lifestyle change in this population.The study enrolled 699 youth who had type 2 diabetes for less than two years and a body mass index (BMI) at the 85th percentile or greater. BMI is a measurement of weight in relation to height. Overweight children have a BMI at the 85th to 94th percentile for their age and sex, while obesity is defined as a BMI at the 95th percentile or more. The TODAY participants had an average BMI at the 98th percentile.Type 2 diabetes in adults and children is closely linked to being overweight, inactive, and having a family history of diabetes. Type 2 diabetes represents 95 percent of diabetes cases in adults, but is much less common in children than type 1 diabetes. Type 1 diabetes, which usually strikes children and young adults, develops when the body's immune system destroys insulin-producing beta cells in the pancreas.The TODAY study centers included:
Children's Hospital Los Angeles
Children's Hospital Colorado, Aurora
University of Oklahoma Health Sciences Center,Oklahoma City
The University of Texas Health Science Center at San Antonio
Texas Children's Hospital, Baylor College of Medicine, Houston
Washington University School of Medicine, St. Louis
Saint Louis University Health Sciences Center, St. Louis
Rainbow Babies & Children's Hospital, Cleveland
Children's Hospital of Pittsburgh
Children's Hospital of Philadelphia
Joslin Diabetes Center at SUNY Upstate Medical University, Syracuse, N.Y.
Yale University, New Haven, Conn.
Massachusetts General Hospital, Boston
Joslin Diabetes Center, Boston
Berrie Center at Columbia University, New York City
Data Coordinating Center at George Washington University, Washington, D.C.
The TODAY study received additional support from BD, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, LifeScan Inc., Pfizer Inc., and Sanofi-aventis.The NIDDK, part of the NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The Institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visitwww.niddk.nih.gov.About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visitwww.nih.gov.

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