Mechanisms of Diabetes Control After Weight Loss Surgery

减肥手术后控制糖尿病的机制

• 批准号: 7034042
• 负责人: BLANDINE B LAFERRERE
• 金额: $ 40.35万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7034042
• 关键词: caloric dietary content; clinical research; clinical trials; diabetes mellitus therapy; diet therapy; dietary restriction; glucose clamp technique; glucose tolerance test; hormone regulation /control mechanism; human subject; human therapy evaluation; incretin hormone; insulin; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; nutrition related tag; obesity; pancreatic islet function; postoperative state; stomach /intestine bypass; stomach emptying; weight loss

DESCRIPTION (provided by applicant): Obesity and type 2 diabetes (DM) are increasing in the US. One third of patients seeking bariatric surgery have DM. Although all surgeries result in significant weight loss and often 'cure' the DM, the rapid onset and the magnitude of the benefits of gastric bypass (GBP) on DM has thus far baffled clinical scientists. Limited data suggest that the improvement in DM after GBP occurs very rapidly, and may not be wholly accounted for by weight loss. Secretion of incretins (gut peptides secreted in response to meals which enhance insulin secretion) is impaired in DM and improves after GBP, possibly due to the specific anatomical changes after this surgery. While some determinants of impaired insulin secretion, such as glucotoxicity, improve equally after diet or surgical weight loss, the improvement in the incretin effect after GBP might be specific to this surgery. We will determine in AIM 1 whether the magnitude of the incretin effect on insulin secretion is greater after GBP than after an equivalent diet-induced weight loss. We will compare, in obese diabetic patients randomized to very low calorie diet or to GBP, the effect of a 3 to 6-week equivalent weight loss on the incretin effect (difference in insulin secretion after comparable oral and intravenous (IV) glucose loads). Experimental data suggest that bypassing the upper gut, rather than weight loss per se, improves glucose tolerance in DM after GBP. AIM 2 will be to determine whether the magnitude of the incretin effect is greater after GBP than after gastric banding (a procedure not known to change the incretins). We will measure the incretin effect before and up to 9 months after GBP or gastric banding. A major determinant of impaired insulin secretion in DM is decreased insulin sensitivity (Si). Diet-induced weight loss improves insulin secretion and Si equally. After GBP, dissociation between the relative changes in insulin secretion and Si has been reported, suggesting a mechanism other than compensation for changes in Si may be involved in insulin secretion. AIM 3 will be to determine whether the changes of insulin secretion (AIRg), relative to changes of Si, are greater after GBP than after gastric banding. We will measure, with IV glucose tolerance tests, before and up to 9 months after surgery, whether, for an equivalent change of Si, AIRg will improve more after GBP than after gastric banding. As more obese diabetic patients undergo GBP, understanding the mechanisms that produce improvement in their diabetes is increasingly important.

描述（由申请人提供）：美国肥胖和2型糖尿病（DM）正在增加。寻求减肥手术的患者中有三分之一患有DM。尽管所有手术都会导致重大体重减轻，并且常常“治愈” DM，但迄今为止，DM的胃搭桥率（GBP）的快速发作和幅度令人困惑。有限的数据表明，GBP后DM的改善非常迅速，并且可能不会完全考虑体重减轻。 DM的分泌（响应增强胰岛素分泌的饮食中分泌的肠道肽）在DM中受损，并且在GBP后改善，这可能是由于该手术后的特定解剖学变化所致。尽管某些胰岛素分泌受损的决定因素，例如糖毒性，在饮食或手术体重减轻后平均改善，但GBP后肠降低剂效应的改善可能是该手术的特异性。我们将在AIM 1中确定肠降血糖素对胰岛素分泌的幅度是否比同等饮食引起的体重减轻后更大。我们将在随机分配至非常低卡路里的肥胖糖尿病患者中，或者与GBP进行比较，这是3至6周的同等体重减轻对肠降凝蛋白作用的影响（可比较的口服和静脉内（IV）葡萄糖负荷后胰岛素分泌的差异）。实验数据表明，绕过上肠而不是体重本身可以提高GBP后DM的葡萄糖耐量。 AIM 2将是确定肠降直染素效应的大小是否比胃谱带之后更大（该过程不知道会改变肠降凝结素）。我们将在GBP或胃束带之前和9个月之前和9个月内测量肠降血糖素效应。 DM中胰岛素分泌受损的主要决定因素是胰岛素敏感性降低（SI）。饮食引起的体重减轻可改善胰岛素分泌和SI。在GBP之后，已经报道了胰岛素分泌与SI的相对变化之间的分离，这表明除了补偿SI变化的赔偿以外的其他机制可能与胰岛素分泌有关。 AIM 3将是确定胰岛素分泌（AIRG）相对于SI的变化的变化是否比胃谱带之后更大。我们将在手术后和9个月前进行IV葡萄糖耐量测试测量，无论是否等效地变化Si，AIRG在GBP之后都比胃束带后会改善。随着越来越多的肥胖糖尿病患者接受英镑，了解糖尿病的改善机制越来越重要。