GLUCOSE METABOLISM IN THE IMMEDIATE AND SHORT-TERM FOLLOW-UP AFTER BARIATRIC

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们建议进行一项研究，以评估接受减肥手术的2型糖尿病患者的糖代谢、胰岛素抵抗、胰岛素分泌和胃肠激素谱的即刻和短期随访结果。具体地说，这项研究旨在调查减肥手术后2型糖尿病改善和可能逆转的机制和比率。我们假设，早在减肥手术实现显著减肥之前，由于几种机制，2型糖尿病患者的葡萄糖代谢就有了显著的改善。我们预计脂肪毒性会降低(即脂肪细胞激素和游离脂肪酸的减少)，导致胰岛素抵抗的改善，或许更重要的是，胰岛素分泌能力显著改善，这不仅是因为胰岛素抵抗的缓解，还因为Roux-en-Y手术对肠道激素的肠岛轴的特殊影响以及随后对细胞功能的影响。这项研究的具体目的将涉及减肥手术后立即的胰腺B细胞功能(静脉注射和口服葡萄糖时胰岛素分泌的测量)、肠道激素分泌和总体葡萄糖代谢的改善率。手术前两周，2型糖尿病患者将接受标准的75克口服葡萄糖耐量试验和高血糖钳夹，以评估在综合临床研究中心(作为门诊就诊)进行的胰岛素分泌和敏感性(全身葡萄糖处置)。术后2天、2周和2个月分别进行高血糖钳夹试验和口服葡萄糖耐量试验(仅限2周和2个月)。在这些测试中，测量将包括血糖、胰岛素、C肽、游离脂肪酸水平和脂肪细胞激素谱(脂联素、瘦素、肿瘤坏死因子和IL-6)。将在空腹和特定的餐后时间进行胃肠激素谱(Ghrelin，胰高血糖素样肽1，GLP-1，胰高血糖素，PYY)。结果将在两组之间进行比较：接受腹腔镜Roux-n-Y胃分流术和胃束带术的患者

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a study for evaluation immediate and short-term follow-up outcome of glucose metabolism; insulin resistance, insulin secretion and gut hormones profile in type 2 diabetic subjects undergoing bariatric surgery. Specifically, this study is designed to investigate mechanisms and rates of improvement and possibly reversal of type 2 diabetes mellitus following bariatric surgery. We hypothesize that long before dramatic weight loss is achieved with bariatric surgery, there is a marked improvement in glucose metabolism in patients with type 2 diabetes due to several mechanisms. We anticipate a decrease of ¿¿lipotoxicity¿¿ (i.e. decrease in adipocyte hormones and free fatty acids), leading to improvement of insulin resistance and perhaps more importantly, a marked improvement in the capacity for insulin secretion due not only to alleviation of insulin resistance, but also by specific effects of Roux-en-Y procedures on the entero-insular axis of gut hormones and subsequent effects on ¿¿-cell function. Specific aim of the study will concern the rate of improvement of pancreatic B cell function (measurement of insulin secretion in response to IV and oral glucose), gut hormone secretion, and overall glucose metabolism immediately following bariatric surgery.Two weeks prior to surgery, type 2 diabetic subjects will undergo a standard 75 gram oral glucose tolerance test and hyperglycemic clamp to assess insulin secretion and sensitivity (whole body glucose disposal) performed in the General Clinical Research Center (as outpatient visits). Following surgery, at 2 days, 2 weeks and 2 months subjects will undergo hyperglycemic clamp and oral glucose tolerance test (2 weeks and 2 months only). During these tests, measurements will include plasma levels of glucose, insulin , C-peptide, free fatty acid levels and adipocyte hormone profile (adiponectin, leptin, TNF-¿¿, and IL-6). A gut hormone profile (ghrelin, glucagons-like-peptide 1 GLP-1, glucagon, PYY) will be performed at fasting and specific postprandial times. Results will be compared between two groups: patients undergoing laposcopic Roux-n-Y gastric bypass and gastric banding