Metabolic and Endocrine Effects of Bariatric Surgery

减肥手术的代谢和内分泌影响

• 批准号: 8457096
• 负责人: Judith Korner
• 金额: $ 34.35万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8457096
• 关键词: Accounting; Acute; Address; Amino Acids; Arginine; Bariatrics; Beta Cell; Biological Assay; Body Composition; Body Weight; Body Weight decreased; Brain; Bypass; C-Peptide; Caloric Restriction; Cell physiology; Chemosensitization; Chronic; Clinical; Collaborations; Data; Development; Diabetes Mellitus; Diet; Disease remission; Dual-Photon Absorptiometries; Endocrine; Energy Metabolism; Enteral; Esthesia; Exclusion; Exposure to; Fasting; Gastrectomy; Gastric Bypass; Glucagon; Glucose; Goals; Hormones; Hunger; Hyperplasia; Indirect Calorimetry; Individual; Infusion procedures; Insulin; Intestines; Islet Cell; Life; Lipids; Maintenance; Mass Fragmentography; Measurement; Measures; Metabolic; Michigan; Modality; Morbid Obesity; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Operative Surgical Procedures; Outcome; Pancreatic Hormones; Pathway interactions; Patients; Physicians; Plasma; Procedures; Rest; Satiation; Site; Small Intestines; Staging; Stomach; Therapeutic; Time; Weight; adiponectin; apolipoprotein A-IV; bariatric surgery; blood glucose regulation; des-n-octanoyl ghrelin; effective therapy; fasting glucose; feeding; follow-up; glucagon-like peptide; glucagon-like peptide 1; glycemic control; human IGFBP2 protein; improved; increased appetite; inflammatory marker; insulin secretion; insulin sensitivity; metabolomics; non-diabetic; obesity treatment; operation; post intervention; prospective; public health relevance; risk benefit ratio; weight maintenance

DESCRIPTION (provided by applicant): Weight loss surgery is usually the most effective treatment of obesity. Roux-en-Y gastric bypass (RYGB) surgery may also be one of the most effective treatments for type 2 diabetes (DM). Laparoscopic gastric banding (LAGB) is another weight loss procedure that results in a lesser degree of weight loss and improvement in glycemic control. In LAGB, the return to euglycemia in T2DM patients is predominantly due to the magnitude of weight loss. In contrast, we have shown that RYGB is associated with changes in gut hormone secretion that may promote decreased appetite, increased satiety, insulin sensitivity and secretion. More recently another bariatric procedure, sleeve gastrectomy (SG), has come into favor as a single procedure, when prior it was the first stage preceding malabsorptive operations. Much less is known about SG, but some data suggest that weight loss and metabolic outcomes, including gut hormone changes, are surprisingly similar to RYGB. Thus, it is likely that neurohormonal mechanisms contribute to greater weight loss and improvement in glucose control after RYGB and SG compared with LAGB and dietary caloric restriction. The main objectives of this proposal are to further delineate the metabolic and endocrine changes that occur after different weight loss modalities. In AIM ONE subjects with DM placed on an in-patient very low calorie diet will be compared with individuals undergoing RYGB and SG before and after equivalent weight loss (7- 10% of body weight) achieved over the same time period (3 wks) in order to determine surgery specific effects on insulin sensitivity and secretion. Subjects will also be followed at 1 year. In AIM TWO, glucagon suppression and maximal islet cell function will be measured by a graded glucose infusion and arginine stimulation before and after RYGB or SG and compared with lean controls. The purpose of this study is to determine if there is evidence of islet cell hyperplasia after RYGB that may occur as a result of chronic exposure to increased concentrations of glucagon-like peptide 1. The main objectives of AIM THREE are to continue characterization of gut hormone and apolipoprotien A-IV secretion after LAGB and RYGB and the relationship to weight loss and appetitive sensations with prospective long-term follow-up. We will also begin characterization after SG. The effect of these procedures on acyl- and des-acyl ghrelin using a specific two-site sandwich assay will be analyzed in collaboration with Dr. Thorner. The objective of AIM FOUR is to investigate alterations in ~200 metabolites, including amino acids, lipid species and glucose intermediates before and after VLCD, LAGB, RYGB, and SG in subjects with and without DM using liquid and gas chromatography and mass spectrometry in collaboration with Dr. Burant and the U of Michigan Metabolomics Core. The ultimate goal is to understand the mechanisms that promote weight loss/maintenance and glucose homeostasis after different weight loss modalities. This information would aid both the patient and physician in the selection of appropriate therapy and guide the development of more effective non-surgical treatments for obesity and DM.

描述（由申请人提供）：减肥手术通常是最有效的治疗肥胖。Roux-en-Y胃旁路术（RYGB）也可能是2型糖尿病（DM）最有效的治疗方法之一。腹腔镜胃束带术（LAGB）是另一种减肥手术，可导致较低程度的体重减轻和血糖控制改善。在LAGB中，T2 DM患者恢复正常主要是由于体重减轻的幅度。相比之下，我们已经证明RYGB与肠道激素分泌的变化有关，这可能会促进食欲下降、饱腹感增加、胰岛素敏感性和分泌。最近，另一种减肥手术，袖状胃切除术（SG），已经成为一个单一的程序，当它之前是第一阶段之前吸收不良的操作。关于SG的了解要少得多，但一些数据表明，体重减轻和代谢结果，包括肠道激素变化，与RYGB惊人地相似。因此，与LAGB和饮食热量限制相比，神经激素机制可能有助于RYGB和SG后更大的体重减轻和葡萄糖控制改善。该建议的主要目的是进一步描述不同减肥方式后发生的代谢和内分泌变化。在AIM ONE中，将接受住院患者极低热量饮食的DM受试者与在相同时间段（3周）内实现的等效体重减轻（体重的7- 10%）之前和之后接受RYGB和SG的个体进行比较，以确定手术对胰岛素敏感性和分泌的特异性影响。受试者还将在1年时接受随访。在AIM TWO中，胰高血糖素抑制和最大胰岛细胞功能将通过RYGB或SG之前和之后的分级葡萄糖输注和精氨酸刺激来测量，并与瘦对照进行比较。本研究的目的是确定RYGB后是否有胰岛细胞增生的证据，这可能是由于长期暴露于浓度增加的胰高血糖素样肽1所致。AIM THREE的主要目标是通过前瞻性长期随访继续表征LAGB和RYGB后肠道激素和载脂蛋白A-IV的分泌，以及与体重减轻和食欲感觉的关系。我们还将在SG后开始表征。将与Thorner博士合作，使用特异性双位点夹心试验分析这些程序对酰基和去酰基生长素释放肽的影响。AIM FOUR的目标是与Burant博士和密歇根大学代谢组学核心合作，使用液相色谱、气相色谱和质谱法研究患有和不患有DM的受试者在VLCD、LAGB、RYGB和SG之前和之后约200种代谢物的变化，包括氨基酸、脂质物质和葡萄糖中间体。最终目标是了解不同减肥方式后促进体重减轻/维持和葡萄糖稳态的机制。这些信息将有助于患者和医生选择适当的治疗方法，并指导开发更有效的肥胖和糖尿病非手术治疗方法。