The Effect of Bariatric Surgery on Carbohydrate Metabolism

描述（由申请人提供）：本申请的总体目的是确定常见减肥手术改变碳水化合物代谢的机制。通常，糖尿病的消退发生在术后早期，然后才出现显著的体重减轻。有人认为减肥手术改变了胰岛素的作用，但很少有研究检查这类患者的胰岛素分泌或餐后葡萄糖通量。最近，已经表明相对短的肠段的旁路与2型糖尿病的缓解相关，这加强了来自被排除的近端肠的激素信号有利地改变葡萄糖代谢的建议。另一种可能性是，营养素的增强的远端肠递送刺激由肠内分泌系统产生的已知或未知激素的分泌过多，从而改善糖尿病。餐后葡萄糖耐量是胰岛素分泌和作用、肠摄取和内脏提取、外周葡萄糖摄取和内源性葡萄糖产生抑制的净结果。目前，人们对各种减肥手术如何改变葡萄糖稳态知之甚少。了解和准确测量减肥手术和膳食量对这些参数的影响是至关重要的。肠内分泌受肠道输送热量速率的影响，也可能受肠神经系统和营养物质直接输送到肠内分泌细胞的速率的调节。直接测量肠道传输也是了解减肥手术如何改变肠道激素分泌的重要组成部分，这些激素可能会改变葡萄糖代谢。 公共卫生相关性：了解旨在减轻体重的外科手术如何改善2型糖尿病中的代谢紊乱的能力，将有助于更好地了解肠道激素如何与热量限制一起改变葡萄糖代谢。这可能会导致新的，有针对性的治疗策略。它已被证明，普通的减肥程序治愈2型糖尿病独立的体重减轻。了解这些干预措施对葡萄糖代谢和GLP-1分泌（以及其他肠道激素）的影响将大大提高我们在糖尿病患者中开发新治疗策略的能力。

DESCRIPTION (provided by applicant): The overall aim of this application is to determine the mechanism(s) by which common bariatric surgical procedures alter carbohydrate metabolism. Very often, resolution of diabetes occurs in the early post-operative period prior to the development of significant weight loss. It has been suggested that bariatric surgery alters insulin action but few studies have examined insulin secretion or postprandial glucose fluxes in such patients. Recently, it has been shown that bypass of relatively short segments of the intestine are associated with remission of type 2 diabetes reinforcing the suggestion that hormonal signals from the excluded proximal gut favorably alter glucose metabolism. Another possibility is that enhanced distal intestinal delivery of nutrients stimulates hypersecretion of known or unknown hormones produced by the enteroendocrine system which ameliorate diabetes. Postprandial glucose tolerance is the net result of insulin secretion and action, intestinal uptake and splanchnic extraction, peripheral glucose uptake and suppression of endogenous glucose production. At the present time, little is known about how the various bariatric surgical procedures alter glucose homeostasis. It is essential that the effect of bariatric surgery and meal size on these parameters be understood and accurately measured. Enteroendocrine secretion is affected by the rate of intestinal delivery of calories and may also be modulated by the enteric nervous system and the rate of direct delivery of nutrients to enteroendocrine cells. Direct measurement of intestinal transit is also an important part of understanding how bariatric surgery alters intestinal secretion of hormones that may alter glucose metabolism. PUBLIC HEALTH RELEVANCE: The ability to understand how surgical procedures designed to produce weight loss ameliorate the metabolic disturbances seen in type 2 diabetes will allow a greater understanding of how intestinal hormones, together with caloric restriction, alter glucose metabolism. This may lead to new, targeted treatment strategies. It has been shown that common bariatric procedures cure type 2 diabetes independent of weight loss. Understanding the effect of these interventions on glucose metabolism and GLP-1 secretion (amongst other gut hormones) will immeasurably increase our ability to develop new treatment strategies in individuals affected with diabetes.