Adolescent Gastric By-Pass and Diabetic Precursors

描述(由申请人提供)： 摘要：超重和肥胖是影响美国的最常见的代谢性疾病，目前有31%的成年人和16%的青少年符合美国疾病控制中心的标准。随着肥胖症的流行，儿童和成人中2型糖尿病的患病率也在增加。对于严重肥胖的成年人来说，治疗2型糖尿病最有效的单一方法可能是减肥手术，这是一种在5岁和60岁时最常见的手术。虽然很明显，快速而深入的减肥可以显著改善成年人的碳水化合物代谢，但目前尚不清楚这些患者的糖尿病可逆程度。青少年和儿童2型糖尿病的病理生理学机制还不是很清楚，目前还没有研究检查手术减肥对严重肥胖年轻人的胰岛素抵抗、胰岛素产生或葡萄糖耐量的影响。然而，减肥手术似乎有可能改善年轻人的这些状况。与中年受试者相比，了解手术减肥对青少年碳水化合物代谢的相对益处对于确定干预的最佳时机很重要。这一知识还可能导致对肥胖引发的糖尿病的关键洞察。在这个项目中，我们将检验这样一种假设，即与成人相比，减肥手术干预将更有效地改善青少年的胰岛素敏感性、胰岛β细胞功能和糖耐量缺陷。报告提出了两个具体目标：1)比较接受减肥手术的重度肥胖(体重指数为40公斤/平方米)青少年和成人的碳水化合物代谢紊乱情况；2)评估青少年和成人纵向(手术减肥期间和手术后)碳水化合物代谢的改善情况，并比较两组改善机制的差异。这些数据将提供有关减肥手术与年龄相关的代谢结果的关键信息，并可能为设计更大规模的研究提供参考，以检查早期减肥手术在治疗甚至预防糖尿病或代谢综合征方面的作用，这些患者是这些危险情况的高危患者。

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.