Mechanisms and Effectiveness of Weight Loss Methods on Diabetes and Sleep Apnea

减肥方法对糖尿病和睡眠呼吸暂停的机制和有效性

• 批准号: 8277284
• 负责人: FREDERICK L BRANCATI
• 金额: $ 49.07万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-28 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277284
• 关键词: Affect; Anatomy; Blood Pressure; Body Weight; Body Weight decreased; Caloric Restriction; Cardiovascular system; Case Series; Central obesity; Clinical Trials; Comorbidity; Control Groups; Controlled Study; Data; Data Collection; Diabetes Mellitus; Diet; Eating; Effectiveness; Effectiveness of Interventions; Energy Intake; Ensure; Fatty acid glycerol esters; Foundations; Future; Gastric Bypass; Glycosylated hemoglobin A; Health; Hormonal; Hormones; Hyperglycemia; Informed Consent; Intervention; Lipids; Manufacturer Name; Measurement; Medical; Metabolic; Methods; Morbidity - disease rate; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Participant; Patients; Pattern; Pharmaceutical Preparations; Physiological; Physiology; Pilot Projects; Polysomnography; Primitive foregut structure; Procedures; Process; Protocols documentation; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recruitment Activity; Reporting; Research; Research Personnel; Serum; Severities; Sleep Apnea Syndromes; Techniques; Third-Party Payer; Visceral; Weight; arm; bariatric surgery; comparative effectiveness; compare effectiveness; cost; design; experience; fasting glucose; gastrointestinal system; glycemic control; health care service utilization; health related quality of life; high risk; improved; intervention effect; moderate obesity; mortality; programs; prospective; public health relevance; response; weight loss intervention

DESCRIPTION (provided by applicant): Obesity is a significant public health problem, which leads to many health-related comorbidities as well as increased morbidity and mortality. Weight loss of at least 5-10% of initial body weight has been shown in short-term trials to improve many obesity-related co-morbidities, and can be achieved through several strategies, including medical weight loss and surgical procedures; yet few studies have rigorously compared the effectiveness of these interventions directly. Furthermore, despite their effectiveness, surgical weight loss approaches are generally not recommended for patients with a BMI <35 kg/m2, regardless of the number or severity of comorbid conditions. Finally, because some surgical procedures, such as the Roux-en Y Gastric Bypass alters the anatomy of the gastrointestinal system and appear to affect its hormonal response to food intake, it is thought that different interventions may result in health improvements through different mechanisms. We hypothesize that a) early metabolic improvements are due to a combination of caloric restriction and changes in the gut-neuroendocrine axis, whereas b) later improvements are related to reductions in obesity and central adiposity. To investigate this hypothesis, we propose a pilot, 6-month, randomized controlled trial in patients with mild to moderate obesity (BMI 30-40 kg/m2) with three arms: 1) medical weight loss (low calorie diet of 800-1200 kcal/day), 2) Roux-en-Y gastric bypass and 3) laparoscopic adjustable gastric banding. To be eligible, patients must have type 2 diabetes (T2DM) and obstructive sleep apnea (OSA), chosen because they are associated with very high risk for cardiovascular complications and mortality. Our pilot study has the following Primary Specific Aims: 1) Assess the feasibility of recruiting, randomizing, delivering the interventions and following patients in a study including both medical weight loss and different surgeries; 2) Examine the comparative effectiveness of the interventions on T2DM and OSA; and 3) Explore the mechanisms for improvement in diabetes, using euglycemic and hyperglycemic clamps, and in sleep apnea, using physiologic characterization of sleep disordered breathing patterns. Additionally, in this pilot study we aim to gather valuable data for the conduct of a future more definitive study. To accomplish these aims, we have created a multi-disciplinary team of established researchers experienced in clinical trials, obesity, bariatric surgery, diabetes, sleep apnea and physiology. We propose state-of-the-art measurement techniques to assess our outcomes. We have partnered with various payers and a meal replacement manufacturer to ensure the feasibility of our proposed study. Ultimately, this line of research will help guide the choice of obesity therapy for patients with obesity-related co-morbidities. PUBLIC HEALTH RELEVANCE: Weight loss is effective in reducing many complications of obesity, with the majority of patients who undergo bariatric surgery having substantial improvements in their weight-related illnesses. We propose a pilot study in 45 subjects with mild to moderate obesity to compare how losing 10% of initial body weight via one of three common weight loss strategies (medical weight loss with a low calorie diet, Roux-en-Y gastric bypass surgery, and adjustable gastric banding) affects diabetes and sleep apnea. While we do not expect this pilot study to provide definitive answers, it will provide valuable information to design a larger trial which will help guide therapy for people with mild-moderate obesity and substantial co-morbidities.

描述（由申请人提供）：肥胖是一个重大的公共卫生问题，它导致许多与健康相关的合并症以及发病率和死亡率的增加。短期试验表明，体重减轻至少初始体重的 5-10% 可以改善许多与肥胖相关的并发症，并且可以通过多种策略来实现，包括药物减肥和外科手术；然而，很少有研究直接严格比较这些干预措施的有效性。此外，尽管手术减肥方法有效，但无论合并症的数量或严重程度如何，通常不建议 BMI <35 kg/m2 的患者使用手术减肥方法。最后，由于一些外科手术（例如 Roux-en Y 胃绕道手术）会改变胃肠系统的解剖结构，并似乎影响其对食物摄入的激素反应，因此人们认为不同的干预措施可能会通过不同的机制改善健康。我们假设a）早期代谢的改善是由于热量限制和肠道神经内分泌轴的变化相结合，而b）后期的改善与肥胖和中心性肥胖的减少有关。为了研究这一假设，我们提出了一项为期 6 个月的随机对照试验，受试者为轻度至中度肥胖 (BMI 30-40 kg/m2) 的患者，分三组：1) 医疗减肥（800-1200 卡路里的低热量饮食） kcal/day), 2) Roux-en-Y 胃绕道术和 3) 腹腔镜可调节胃束带术。为了符合资格，患者必须患有 2 型糖尿病 (T2DM) 和阻塞性睡眠呼吸暂停 (OSA)，之所以选择这些患者是因为它们与心血管并发症和死亡率的极高风险相关。我们的试点研究有以下主要具体目标： 1) 评估在一项研究中招募、随机化、提供干预措施和跟踪患者的可行性，包括医疗减肥和不同的手术； 2) 检验T2DM和OSA干预措施的比较有效性； 3) 使用正常血糖和高血糖钳夹探索改善糖尿病的机制，并使用睡眠呼吸障碍模式的生理特征探索改善睡眠呼吸暂停的机制。此外，在这项试点研究中，我们的目标是收集有价值的数据，以便将来进行更明确的研究。为了实现这些目标，我们创建了一个由在临床试验、肥胖、减肥手术、糖尿病、睡眠呼吸暂停和生理学方面经验丰富的资深研究人员组成的多学科团队。我们提出最先进的测量技术来评估我们的结果。我们与各个付款人和代餐制造商合作，以确保我们提出的研究的可行性。最终，这一系列研究将有助于指导患有肥胖相关合并症的患者选择肥胖疗法。 公共卫生相关性：减肥可有效减少肥胖的许多并发症，大多数接受减肥手术的患者与体重相关的疾病都有显着改善。我们提议对 45 名轻度至中度肥胖受试者进行一项试点研究，比较如何通过三种常见减肥策略（低热量饮食的药物减肥、Roux-en-Y 胃绕道手术、和可调节胃束带）会影响糖尿病和睡眠呼吸暂停。虽然我们不期望这项试点研究提供明确的答案，但它将提供有价值的信息来设计更大规模的试验，这将有助于指导轻度至中度肥胖和严重合并症患者的治疗。

项目成果

Screening and diagnosis of micronutrient deficiencies before and after bariatric surgery.

• DOI: 10.1007/s11695-013-0919-x
• 发表时间: 2013-10
• 期刊: OBESITY SURGERY
• 影响因子: 2.9
• 作者: Gudzune, Kimberly A.;Huizinga, Mary M.;Chang, Hsien-Yen;Asamoah, Vivian;Gadgil, Meghana;Clark, Jeanne M.
• 通讯作者: Clark, Jeanne M.

The Role of Laboratory Testing in Differentiating Type 1 Diabetes from Type 2 Diabetes in Patients Undergoing Bariatric Surgery.

实验室检测在区分接受减肥手术的患者中 1 型糖尿病和 2 型糖尿病方面的作用。

• DOI: 10.1007/s11695-017-2804-5
• 发表时间: 2018
• 期刊: Obesity surgery
• 影响因子: 2.9
• 作者: Pilla,ScottJ;Maruthur,NisaM;Schweitzer,MichaelA;Magnuson,ThomasH;Potter,JamesJ;Clark,JeanneM;Lee,ClareJ
• 通讯作者: Lee,ClareJ