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普通减肥外科手术改变碳水化合物代谢的机制。通常，糖尿病的缓解发生在术后早期，在体重显著减轻之前。有人认为，减肥手术可以改变胰岛素的作用，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，有研究表明，相对较短的肠段旁路治疗与2型糖尿病的缓解有关，这进一步表明，来自被排除在外的近端肠道的激素信号有利于改变葡萄糖代谢。另一种可能性是，营养物质远端肠道输送的增强刺激肠内分泌系统产生的已知或未知激素的高分泌，从而改善糖尿病。餐后葡萄糖耐量是胰岛素分泌和作用、肠道摄取和内脏提取、外周葡萄糖摄取和抑制内源性葡萄糖产生的最终结果。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。肠内分泌分泌受到肠内热量输送速率的影响，也可能受到肠神经系统和营养物质直接输送到肠内分泌细胞速率的调节。肠道运输的直接测量也是了解减肥手术如何改变肠道分泌可能改变葡萄糖代谢的激素的重要组成部分。

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.