EFFECTS OF BARIATRIC SURGERY ON GLUCOSE HOMEOSTASIS IN TYPE-2 DIABETES

减肥手术对 2 型糖尿病患者葡萄糖稳态的影响

• 批准号: 8386045
• 负责人: Samuel Klein
• 金额: $ 19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8386045
• 关键词: Achievement; Adipose tissue; Bariatrics; Body Weight; Body Weight decreased; Cell physiology; Cells; Clinical; Clinical Practice Guideline; Diabetes Mellitus; Diagnosis; Diet; Disease; Euglycemic Clamping; Gastric Bypass; Glucose; Glucose Clamp; Guidelines; Infusion procedures; Ingestion; Insulin; Knowledge; Label; Lipolysis; Liver; Metabolic; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Pancreas; Patient Selection; Patients; Physiological; Procedures; Public Health; Resolution; Risk Factors; Skeletal Muscle; Staging; Testing; Tracer; Wit; absorption; bariatric surgery; base; blood glucose regulation; glucose metabolism; glucose production; glucose uptake; human subject; illness length; insulin secretion; insulin sensitivity; metabolic abnormality assessment; response; stable isotope

DESCRIPTION (provided by applicant): Obesity is an important risk factor for type 2 diabetes mellitus (T2DM), which is a major public health problem in the U.S. Bariatric surgery is currently the most effective weight loss therapy for obesity. Furthermore, Roux-en-Y gastric bypass (RYGB) is most commonly performed bariatric procedure in the US and worldwide and results in resolution of T2DM in ~80% of patients. It has been suggested that the duration of T2DM diagnosis before RYGB surgery is a predictor for diabetes resolution. However, this hypothesis has never been adequately evaluated in human subjects. Therefore, the primary purpose of this proposal is to provide a better understanding of the effect of bariatric surgery-induced weight loss on insulin action and pancreatic ¿-cell function as it relates to the duration of T2DM diagnosis (recent vs. longstanding). We hypothesize that the weight loss provided by RYGB surgery will have greater effects on insulin sensitivity and ¿ -cell function in severely obese wit recently diagnosed T2DM than those with longstanding disease. The following specific aims will be evaluated in two groups of severely obese patients with T2DM undergoing RYGB surgery: 1) obese patients with "recently" diagnosed T2DM (d 5 years) and 2) obese patients with "longstanding" T2DM (e 10 years). Metabolic studies will be performed before RYGB and repeated after subjects have lost ~ 20% of total body weight. Specifically we aim to: 1. Evaluate the effect of weight loss after RYGB on insulin action in liver (suppression of glucose production), skeletal muscle (stimulation of glucose uptake) and adipose tissue (suppression of lipolysis). This aim will be evaluated by conducting a two-stage hyperinsulinemic euglycemic clamp procedure, in conjunction with stable isotopically-labeled tracer infusion. and 2. Evaluate the effect of RYGB induced weight loss on pancreatic ¿-cell response. This aim will be evaluated by conducting a Mixed Meal Tolerance Test (MMTT), in conjunction with stable isotope tracer ingestion and infusion, to assess absorption of ingested glucose, suppression of endogenous glucose production, and insulin secretion in response to the meal. The achievement of these aims will provide important physiological and clinical knowledge regarding the effect of bariatric (RYGB) surgery on T2DM as it relates of the duration of this condition. Successful completion of this study could influence the current clinical guidelines for the selection of patients for bariatric surgery. The achievement of these aims will provide important physiological and clinical knowledge regarding the effect of bariatric (RYGB) surgery on T2DM as it relates of the duration of this condition. The results from this study could influence curren clinical practice guidelines for the selection of patients who have T2DM for bariatric surgery based on the duration of disease. PUBLIC HEALTH RELEVANCE: Obesity is an important risk factor for type 2 diabetes mellitus (T2DM), which is a major public health problem in the U.S. Bariatric surgery is currently the most effective weight loss therapy for obesity that results in resolution of T2DM in ~80% of patients. We aim to determine the effects of surgical induced weight loss on glucose metabolism as it relates to the duration of T2DM diagnosis (recent vs. longstanding).

描述（由适用提供）：肥胖是2型糖尿病（T2DM）的重要危险因素，这是美国减肥手术的主要公共卫生问题，目前是肥胖症的最有效的减肥疗法。此外，Roux-en-Y胃旁路（RYGB）是美国和全球最常进行的减肥手术，并导致约80％的患者在约80％的患者中解决T2DM。已经提出，RYGB手术前T2DM诊断的持续时间是糖尿病分辨率的预测因子。但是，这种假设从未在人类受试者中得到充分评估。因此，该提案的主要目的是更好地理解减肥手术引起的体重减轻对胰岛素作用和胰腺作用的影响，因为它与T2DM诊断的持续时间有关（最近与长期存在）。我们假设RYGB手术提供的体重减轻将对胰岛素敏感性和最近诊断为T2DM的胰岛素敏感性和细胞功能更大，而不是长期存在的疾病。将在两组严重肥胖的T2DM接受RYGB手术的患者中评估以下具体目标：1）肥胖患有“最近”诊断T2DM（D 5年）和2）肥胖患者肥胖患有“长期” T2DM（E 10年）。代谢研究将在RYGB之前进行，并在受试者损失总体体重的20％后重复。具体而言，我们的目的是：1。评估RYGB后体重减轻对肝脏胰岛素作用（抑制葡萄糖产生），骨骼肌（刺激葡萄糖摄取）和脂肪组织（抑制脂解的刺激）的影响。通过稳定的同位素标记的示踪剂输注，将通过进行两阶段高胰岛素优质糖夹程序来评估该目标。和2。评估RYGB诱导的体重减轻对胰腺反应的影响。将通过进行混合饮食耐受性测试（MMTT）以及稳定的同位素示踪剂摄入和输注来评估该目标，以评估摄入的葡萄糖的损失，抑制内源性葡萄糖的产生以及胰岛素分泌。这些目标的实现将提供有关减肥（RYGB）手术对T2DM的影响的重要物理和临床知识，因为它与此疾病的持续时间有关。这项研究的成功完成可能会影响当前的减肥手术患者选择的临床指南。这些目标的实现将提供有关减肥（RYGB）手术对T2DM的影响的重要物理和临床知识，因为它与此疾病的持续时间有关。这项研究的结果可能会影响Curren的临床实践指南，以选择基于疾病持续时间进行减肥手术T2DM的患者。 公共卫生相关性：肥胖是2型糖尿病（T2DM）的重要危险因素，这是美国减肥手术的主要公共卫生问题，目前是肥胖症的最有效的减肥疗法，可导致约80％患者在约80％的患者中分辨出T2DM。我们旨在确定手术诱导的体重减轻对葡萄糖代谢的影响，因为它与T2DM诊断持续时间有关（最近与长期存在）。