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（T2DM）缓解的机制尚不清楚。胃肠激素肠促胰岛素水平及其对胰岛素分泌的影响，在T2DM中受损，在GBP后显著增加。肠促胰岛素的变化似乎是由GBP的解剖学改变而不是体重减轻引起的。本提案的目的是研究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和肠道肽变化在随机分配到GBP或GB的T2DM患者的短期和长期发病率中的作用。AIM 1将比较GBP和GB对等效减重10 kg后肠促胰岛素水平和效果的短期影响，检验GBP后肠促胰岛素水平和效果比GB后增加更多的假设。AIM 2将研究口服葡萄糖后和24小时多餐饮食期间肠促胰岛素水平的长期变化及其影响，GBP和GB前和2年后，验证GBP后平均肠促胰岛素水平高于GB后的假设。AIM 3将研究胰岛素分泌对IV葡萄糖的反应（AIRg）和胰岛素敏感性（Si）的变化，用最小模型测量，在GBP和GB后2年，测试假设对于Si的等效增加，GBP后AIRg的增加大于GB。公共卫生相关性：肥胖和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）可使体重减轻50-70%，84%的2型糖尿病（T2DM）得到缓解。GBP后糖尿病改善的机制尚不清楚。血糖控制发生在显著的体重减轻之前很久，这表明手术的性质，而不是体重减轻，是导致T2DM改善的原因。最近的数据显示，胃肠激素（肠促胰岛素）在GBP术后糖尿病改善中的作用，但在另一种手术胃束带（GB）后却没有。我们建议在病态肥胖和T2DM患者中，随机分为GBP或GB，研究手术短期和长期对肠促胰岛素水平和效果的影响，胰岛素分泌对静脉葡萄糖和糖尿病控制的反应。我们希望将我们的发现应用于治疗肥胖和2型糖尿病的可能的医学选择。

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.