Metabolic and Endocrine Effects of Bariatric Surgery

减肥手术的代谢和内分泌影响

• 批准号: 8245699
• 负责人: Judith Korner
• 金额: $ 35.6万
• 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/8245699
• 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. PUBLIC HEALTH RELEVANCE: Together with an exponential increase in morbid obesity is an increase in individuals with type 2 diabetes mellitus and an increase in individuals undergoing bariatric surgery to treat these chronic life-threatening conditions. The objective of these studies is to gain an understanding of mechanisms that promote weight loss, improved glucose control and/or remission of diabetes. The ultimate goal is not only to identify non- surgical therapeutic pathways for obesity and diabetes but also to identify clinical variables that are associated with surgical outcomes that will maximize the risk: benefit ratio for individuals considering bariatric surgery as a treatment for both obesity and diabetes.

描述（由申请人提供）：减肥手术通常是治疗肥胖最有效的方法。 Roux-en-Y胃绕道手术（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，可减轻体重并改善血糖控制。在 LAGB 中，T2DM 患者恢复正常血糖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，肠道激素分泌的变化可能会促进食欲下降、饱腹感增加、胰岛素敏感性和分泌增加。最近，另一种减肥手术——袖状胃切除术（SG）作为单一手术受到青睐，而在此之前它是吸收不良手术之前的第一阶段。人们对 SG 知之甚少，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血糖控制的改善。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 ONE 中，住院期间接受极低热量饮食的 DM 受试者将与在同一时间段（3 周）内实现同等体重减轻（体重的 7-10%）之前和之后接受 RYGB 和 SG 的受试者进行比较以确定手术对胰岛素敏感性和分泌的具体影响。还将对受试者进行一年后的随访。在目标二中，将通过 RYGB 或 SG 前后的分级葡萄糖输注和精氨酸刺激来测量胰高血糖素抑制和最大胰岛细胞功能，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，这种增生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。目标三的主要目标是继续表征肠道激素LAGB 和 RYGB 后载脂蛋白 A-IV 的分泌，以及与体重减轻和食欲的关系以及前瞻性长期随访。我们还将在 SG 之后开始表征。将与 Thorner 博士合作，使用特定的双位点夹心测定法分析这些程序对酰基和去酰基生长素释放肽的影响。 AIM 4 的目标是使用液相色谱、气相色谱和质谱联用，研究患有和不患有 DM 的受试者在 VLCD、LAGB、RYGB 和 SG 前后约 200 种代谢物的变化，包括氨基酸、脂质种类和葡萄糖中间体与 Burant 博士和密歇根大学代谢组学核心一起。最终目标是了解不同减肥方式后促进减肥/维持和葡萄糖稳态的机制。这些信息将帮助患者和医生选择合适的治疗方法，并指导开发更有效的肥胖和糖尿病非手术治疗方法。 公共卫生相关性：随着病态肥胖呈指数级增长，患有 2 型糖尿病的人数也在增加，并且接受减肥手术来治疗这些慢性危及生命的疾病的人数也在增加。这些研究的目的是了解促进体重减轻、改善血糖控制和/或缓解糖尿病的机制。最终目标不仅是确定肥胖和糖尿病的非手术治疗途径，而且还确定与手术结果相关的临床变量，这些变量将最大限度地提高考虑减肥手术作为肥胖和糖尿病治疗方法的个人的风险：收益比。