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，这导致许多与健康有关的合并症以及发病率和死亡率的提高。在短期试验中已经显示了至少5-10％的初始体重的体重，以改善许多与肥胖相关的合并症，并且可以通过多种策略（包括医疗体重减轻和外科手术程序）实现；然而，很少有研究直接比较这些干预措施的有效性。此外，尽管它们有效，但对于BMI <35 kg/m2的患者，无论合并症的数量或严重程度如何，通常不建议使用手术减肥方法。最后，由于某些外科手术（例如Roux-en Y胃旁路）改变了胃肠道系统的解剖结构，并且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通过不同的机制导致健康改善。我们假设a）a）早期代谢改善是由于热量限制和肠道神经内分泌轴的变化的结合，而b）b）后来的改善与肥胖和中央肥胖的减少有关。为了研究这一假设，我们提出了一个试验，6个月，随机对照试验，对中度至中度肥胖症患者（BMI 30-40 kg/m2），使用三个臂：1）医疗体重减轻（低热量饮食为800-1200 kcal/Day），2）roux-en-en-en-en-en-en-en-en-en-en-en-en-en-en-en-en y-en-en-en-en-en-en-en-en gastric and pass和laparossscop castrics castrics castric castric castric castric castric castric castric castric castring。为了符合条件，患者必须患有2型糖尿病（T2DM）和阻塞性睡眠呼吸暂停（OSA），因为它们与心血管并发症和死亡率非常高的风险相关。我们的试点研究具有以下主要特定目的：1）评估招募，随机化，提供干预措施并在一项研究中关注患者的可行性，包括医疗体重减轻和不同的手术； 2）检查对T2DM和OSA的干预措施的比较有效性； 3）使用睡眠不足的呼吸模式的生理表征，使用尤利克血糖和高血糖夹来探索改善糖尿病的机制，以及睡眠呼吸暂停。此外，在这项试点研究中，我们旨在收集有价值的数据，以进行未来的更确定的研究。为了实现这些目标，我们创建了一个由临床试验，肥胖，减肥手术，糖尿病，睡眠呼吸暂停和生理学的知名研究人员组成的多学科团队。我们提出了最先进的测量技术来评估我们的结果。我们已经与各种付款人和更换膳食制造商合作，以确保我们拟议的研究的可行性。最终，这项研究将有助于指导与肥胖相关的合并症患者的肥胖症选择。 公共卫生相关性：体重减轻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在体重相关疾病方面有很大改善。我们提出了一项针对45名轻度至中度肥胖症受试者的试点研究，以比较通过三种常见的体重减轻策略之一（低卡路里饮食，Roux-en-Y Y-Y-Y胃旁路手术和可调节的胃谱带）如何减轻初始体重的10％，并会影响糖尿病和睡眠呼吸暂停。尽管我们不希望这项试点研究能够提供明确的答案，但它将提供有价值的信息来设计更大的试验，这将有助于指导肥胖症患者和大量合并症患者的治疗。

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