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）：减肥手术通常是肥胖症的最有效治疗方法。 roux-en-y胃旁路（RYGB）手术也可能是2型糖尿病（DM）最有效的治疗方法之一。腹腔镜胃带（LAGB）是另一种体重减轻过程，导致血糖控制的体重减轻和改善程度较小。在LAGB中，T2DM患者的尤利克血症返回主要是由于体重减轻的幅度。相比之下，我们已经表明RYGB与肠道激素分泌的变化有关，这些变化可能促进食欲降低，饱腹感，胰岛素敏感性和分泌。最近，另一种减肥手术，即袖胃切除术（SG），在此之前是单一程序，而在此之前，它是在不良手术之前的第一阶段。关于SG的了解要少得多，但是一些数据表明，包括肠径变化在内的体重减轻和代谢结果与RYGB非常相似。因此，与LAGB和饮食热量限制相比，神经激素机制可能有助于更大的体重减轻和葡萄糖控制的改善。该提案的主要目标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中，将DM放置在患者中非常低的卡路里饮食中的一个受试者将与接受RYGB和SG的个体在同一时期（3周）中获得的同等减肥（占体重的7-10％）之前和之后进行比较，以确定手术对胰岛素敏感性和分泌的特异性影响。受试者也将在1年内遵循。在目标二中，胰高血糖素抑制和最大胰岛细胞功能将通过在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，并与瘦对照组进行比较。这项研究的目的是确定RYGB后胰岛细胞增生是否有证据，这可能是由于长期暴露于增加胰高血糖素样肽1的浓度而发生的。目标三的主要目标是继续表征肠激素和apolipoprotien a-iv a-iv分泌后，在落后和rygb和rygb的探究中，与体重减轻和相关感随访和相关性随访及其相关性。我们还将在SG之后开始表征。这些程序对使用特定的两点三明治测定法的影响将与Thorner博士合作分析。目标四的目的是研究约200个代谢产物的变化，包括氨基酸，脂质物种和葡萄糖中间体在VLCD，LAGB，LAGB，RYGB和SG之后，使用和不使用DM的受试者使用液体色谱和气体色谱和质谱法与Burant博士以及Burant和Michigan代表核心的U型DM进行。最终目标是了解不同体重减轻方式后促进减肥/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疗法，并指导开发更有效的肥胖症和DM的非手术治疗方法。