Mechanisms of Diabetes Control After Weight Loss Surgery

描述（由申请人提供）：胃旁路手术（GBP）后2型糖尿病（T2 DM）缓解的机制尚不清楚。GBP后，肠激素肠促胰岛素水平及其对胰岛素分泌的影响（在T2 DM中受损）显著增加。肠促胰岛素的变化可能与GBP的解剖结构改变有关，而与体重减轻无关。本建议的目的是调查GBP和胃束带（GB）影响血糖控制的不同机制。我们希望了解体重减轻与肠肽变化在随机分配至GBP或GB的T2 DM患者的短期和长期发病率中的作用。AIM 1将比较GBP和GB对肠促胰岛素水平的短期影响以及等效10 kg体重减轻后的影响，检验GBP后肠促胰岛素水平和影响增加幅度大于GB后的假设。目的2将研究GBP和GB之前和之后2年，口服葡萄糖后和24小时多餐饮食期间肠促胰岛素水平的长期变化和影响，检验GBP后平均肠促胰岛素水平高于GB后的假设。目的3将研究GBP和GB后2年胰岛素分泌对IV葡萄糖（AIRg）和胰岛素敏感性（Si）的响应变化，通过最小模型测量，检验对于Si的等效增加，AIRg在GBP后比GB后增加更多的假设。公共卫生相关性：肥胖症和2型糖尿病患病率的增加导致寻求手术减肥的患者数量激增。胃旁路手术（GBP）导致体重减轻50-70%，84%的病例2型糖尿病（T2 DM）消退。GBP后糖尿病改善的机制尚不清楚。在显著的体重减轻之前很久就发生了血糖控制，这表明该程序的性质而不是体重减轻是T2 DM改善的原因。最近的数据已经指出了肠促胰岛素在GBP后糖尿病改善中的作用，而不是在另一种类型的手术胃束带（GB）后。我们建议在病态肥胖和T2 DM患者中，随机分配至GBP或GB，研究手术对肠促胰岛素水平和作用的短期和长期影响，以及对IV葡萄糖和糖尿病控制的胰岛素分泌的影响。我们希望将我们的研究结果应用于治疗肥胖和T2 DM的可能的医学替代方案。

DESCRIPTION (provided by applicant): The mechanisms of type 2 diabetes (T2DM) remission after gastric bypass surgery (GBP) are unclear. The levels of the gut hormones incretins and their effect on insulin secretion, which is impaired in T2DM, markedly increase after GBP. The anatomical changes of GBP, rather than weight loss, seem to be responsible for the changes of incretins. The objective of this proposal is to investigate the different mechanisms by which GBP and gastric banding (GB) affect glucose control. We wish to understand the role of weight loss versus changes in gut peptides in the short and long term morbidity in patients with T2DM randomized to GBP or GB. AIM 1 will compare the short term effect of GBP and GB on incretin levels and effect after an equivalent 10 kg weight loss, testing the hypothesis that incretin levels and effect will increase more after GBP than after GB. AIM 2 will study the long-term changes in the incretin levels and effect after oral glucose and during a 24-h multiple meal diet, before and 2 years after GBP and GB, testing the hypothesis that mean incretin levels is greater after GBP than after GB. AIM 3 will study the changes of insulin secretion in response to IV glucose (AIRg) and insulin sensitivity (Si), measured by the minimal model, 2 years after GBP and GB, testing the hypothesis that for an equivalent increase of Si, AIRg will increase more after GBP than after GB. PUBLIC HEALTH RELEVANCE: The increased prevalence of obesity and type 2 diabetes has resulted in a surge in the number of patients seeking surgical weight loss. Gastric bypass surgery (GBP) results in 50-70% excess body weight loss with resolution of type 2 diabetes (T2DM) in 84% of cases. The mechanisms by which diabetes improves after GBP are unclear. Glycemic control occurs long before significant weight loss, suggesting that the nature of the procedure, rather than the weight loss, is responsible for the T2DM improvement. Recent data have singled out the role of the gut hormones known as incretins in diabetes improvement after GBP, but not after another type of surgery, gastric banding (GB). We propose to study, in patients with morbid obesity and T2DM, randomized to GBP or GB, the effect of the surgery in the short and the long term on incretins levels and effect, insulin secretion in response to IV glucose and diabetes control. We wish to apply our findings to possible medical alternatives for the treatment of obesity and T2DM.