Adolescent Gastric By-Pass and Diabetic Precursors

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DESCRIPTION (provided by applicant): Abstract: Overweight and obesity are the most common metabolic disorders affecting the U.S. with 31% of adults and 16% of adolescents now meeting Centers for Disease Control criteria for these conditions. As the obesity epidemic has unfolded, so too has the increase in prevalence of type 2 diabetes in children and adults. The single most effective treatment for type 2 diabetes in severely obese adults may be bariatric surgery, a procedure that is most commonly performed in the 5th and 6th decades of life. While it is clear that rapid and profound weight loss can significantly improve carbohydrate metabolism in adults, it is not clear to what degree diabetes is reversible in these patients. The pathophysiology of type 2 diabetes in adolescents and children is not well understood and no studies have yet examined the effect of surgical weight loss on insulin resistance, insulin production, or glucose tolerance in severely obese young people. However, it seems likely that bariatric surgery could improve these conditions in youth. Understanding the relative benefits of surgically induced weight reduction on carbohydrate metabolism in adolescents compared to middle-aged subjects is important for determining optimal timing of this intervention. This knowledge may also lead to key insights into obesity-induced diabetes. In this project we will test the hypothesis that bariatric surgical intervention will more effectively improve defects in insulin sensitivity, pancreatic beta cell function, and glucose tolerance in adolescents compared to adults. Two specific aims are proposed 1) to compare the derangements of carbohydrate metabolism among very severely obese (body mass index >40 kg/m2) adolescents and adults referred for bariatric surgery; and 2) To assess improvement in carbohydrate metabolism longitudinally (during and after surgical weight loss) in adolescents and adults and compare differences in the mechanisms of improvement between the two groups. These data will provide critical information about age-related metabolic outcomes of bariatric surgery and could inform the design of larger studies to examine the role of early bariatric surgery for treatment or even prevention of diabetes or the metabolic syndrome in patients at high risk for these dangerous conditions.