The Effect of Bariatric Surgery on Carbohydrate Metabolism

描述(申请人提供)：本申请的总体目标是确定常见的减肥外科手术改变碳水化合物代谢的机制(S)。通常情况下，糖尿病的缓解发生在术后早期，在体重显著减轻之前。有研究表明，减肥手术改变了胰岛素的作用，但很少有研究研究这类患者的胰岛素分泌或餐后葡萄糖流量。最近，有研究表明，绕过相对较短的肠段与2型糖尿病的缓解有关，这进一步表明，来自被排除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了由肠道内分泌系统产生的已知或未知激素的过度分泌，从而改善了糖尿病。餐后糖耐量是胰岛素分泌和作用、肠道摄取和内脏提取、外周葡萄糖摄取和内源性葡萄糖生成抑制的净结果。目前，人们对各种减肥手术如何改变血糖稳态知之甚少。了解和准确测量减肥手术和膳食大小对这些参数的影响是至关重要的。肠内分泌受肠道卡路里输送速率的影响，也可能受肠道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。对肠道转运的直接测量也是了解减肥手术如何改变肠道激素分泌从而改变葡萄糖代谢的重要部分。 与公共健康相关：了解旨在实现减肥的外科手术如何改善2型糖尿病的代谢紊乱的能力，将使人们更好地了解肠道激素和热量限制如何改变葡萄糖代谢。这可能导致新的、有针对性的治疗策略。已有研究表明，常见的减肥手术可以治疗不依赖于体重减轻的2型糖尿病。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，将极大地提高我们为糖尿病患者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.