Exercise Dose-Response Effects in Prediabetes: Responses and Mechanisms

糖尿病前期的运动剂量反应效应：反应和机制

• 批准号: 8245188
• 负责人: WILLIAM E KRAUS
• 金额: $ 57.3万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-29 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8245188
• 关键词: Accounting; Address; Adipose tissue; Adult; American; American Heart Association; Biochemical; Biopsy; Biopsy Specimen; Body Weight decreased; Cardiovascular Diseases; Clinical; Clinical Research; Coronary; Country; Deterioration; Diabetes Mellitus; Diabetes prevention; Diet; Dietary Intervention; Dose; Dyslipidemias; Educational Intervention; Effectiveness; Exercise; Exercise Physiology; Fasting; Fatty acid glycerol esters; Functional Imaging; Gender; Glucose; Goals; Gold; Health; Hepatic; Hepatic Mass; Impaired fasting glycaemia; Individual; Institute of Medicine (U.S.); Insulin; Intervention; Investigation; Jogging; Kinetics; Life Style; Lifestyle Therapy; Linear Models; Lipids; Lipoproteins; Measures; Mediating; Metabolic; Metabolic syndrome; Metabolism; Mitochondria; Modeling; Molecular; Monitor; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Nutrition Assessment; OGTT; Obesity; Outcome Measure; Pancreas; Performance; Physiological; Physiology; Population; Population Study; Prediabetes syndrome; Prevention; Prevention therapy; Publications; Randomized; Relative (related person); Research; Risk; Risk Factors; Running; Skeletal Muscle; Sports Medicine; Testing; Time; Tissues; Training; Training Programs; Triglycerides; Visceral; Walking; X-Ray Computed Tomography; arm; blood glucose regulation; cardiovascular risk factor; clinically significant; college; density; design; diabetes prevention program; diabetes risk; diabetic; diabetic cardiomyopathy; diet and exercise; economic cost; enzyme activity; fasting plasma glucose; glucose output; glucose production; human subject; impaired glucose tolerance; improved; indexing; insulin mediators; insulin sensitivity; intravenous glucose tolerance test; lifestyle intervention; metabolomics; mitochondrial dysfunction; muscle metabolism; oral glucose tolerance; organic acid; prevent; primary outcome; programs; public health relevance; response; secondary outcome; vastus lateralis

DESCRIPTION (provided by applicant): The landmark Diabetes Prevention Program (DPP) has established a "gold standard" therapy for prevention of type 2 diabetes (T2DM) in prediabetics, i.e., lifestyle changes that include diet, exercise and weight loss. Despite the advances to the prevention of T2DM that this study provides, there remain important questions about 1) how much of the effect was due to the exercise program; 2) what is the optimal/minimal exercise amount and exercise intensity for prediabetics; and 3) what might be the specific physiologic benefits underlying exercise training in preventing the progression to T2DM in prediabetic subjects. Using a controlled, randomized design, we propose to compare the effects of three six-month exercise-training programs involving different amounts and intensities of exercise on measures and mechanisms of glucose control in prediabetics, and to evaluate the overall effectiveness of these three exercise-only interventions by comparing them to a six-month clinical lifestyle intervention (CLI) that contains the components of the DPP but which is of much shorter duration. The study population will consist of prediabetics with impaired fasting glucose (IFG-fasting plasma glucose 100-125 mg/dl), with or without impaired glucose tolerance-IGT. All subjects will be randomized to one of the following exercise training or lifestyle intervention groups for six months: 1) Low-Dose/Moderate-Intensity: 150 min/wk of moderate intensity exercise, 2) High-Dose/Moderate-Intensity: 300 min/wk of moderate intensity exercise, 3) High-Dose/Vigorous-Intensity: 200 min/wk of vigorous intensity exercise (amount calorically equal to High-Dose, i.e., Group 2 above), 4) Clinical Lifestyle Intervention (diet, exercise & weight loss): 150 min/wk of moderate intensity exercise (same as Group 1) plus diet, and a 6% weight loss goal. Aim 1. To determine the effectiveness of exercise only interventions differing in amount and intensity on measures of glucose control: fasting plasma glucose, oral glucose tolerance, and insulin sensitivity. Aim 2. To determine the effects of different amounts and intensities of exercise on important secondary diabetic and cardiometabolic risk factors. Aim 3. To determine the effects of different amounts and intensities of exercise on mechanisms of glucose control: a) hepatic glucose production; b) ectopic fat distribution and amount, c) mitochondrial dysfunction in skeletal muscle - evaluated via the performance of metabolomics on muscle biopsy samples from the vastus lateralis d) determinants of glucose and nonesterified fatty acid kinetics during an IVGTT and OGTT. PUBLIC HEALTH RELEVANCE: This is an exercise study in human subjects on the path to developing diabetes that addresses three questions. First, compared to a clinical lifestyle program that includes diet and dedicated weight loss, how does an exercise program alone compare? Second, is a walking program, and lots of it, as good or better than a jogging program? Third, how do the exercise-induced benefits accrue? The answers to these questions should have an impact on the prevention and treatment of diabetes.

描述（由申请人提供）：Landmark糖尿病预防计划（DPP）已建立了一种预防糖尿病前期2型糖尿病（T2DM）的“黄金标准”疗法，即，包括饮食，运动和体重减轻的生活方式变化。尽管这项研究提供了预防T2DM的进步，但仍然存在有关锻炼计划造成多少效果的重要问题； 2）糖尿病前期的最佳/最小运动量和运动强度是多少； 3）在防止糖尿病前期受试者中进展为T2DM的锻炼训练的基本特定生理益处可能是什么。我们建议使用受控的，随机的设计，比较涉及不同数量和锻炼的三个六个月运动训练计划对糖尿病学中葡萄糖控制的度量和机制的影响，并评估这三个锻炼的总体有效性，以将它们与六个月的临床干预（cli）进行比较，以使其与六个月的临床干预（cli）进行比较（cli），但cli的培训（cli）的一部分（cli）的一小部分（cli）的培训率是一小部分。研究人群将包括糖尿病前的糖尿病前葡萄糖（饮用IFG葡萄糖100-125 mg/dL），有或没有葡萄糖耐受性受损的情况。所有受试者将在六个月内随机分配到以下运动训练或生活方式干预组之一：1）低剂量/中等强度：150分钟/周中等强度练习，2）高剂量/中度强度：300分钟/WK中等强度的锻炼，3）高剂量/剧烈强度的高剂量/剧烈强度（200分钟），高量/周。临床生活方式干预（饮食，运动和体重减轻）：150分钟/周中强度运动（与第1组相同）加饮食，减肥目标6％。目的1。仅确定运动干预措施的有效性，其葡萄糖控制度量的数量和强度不同：禁食等离子体葡萄糖，口服葡萄糖耐受性和胰岛素敏感性。目的2。确定运动的影响和锻炼强度对重要的继发性糖尿病和心脏代谢危险因素的影响。目的3。确定不同量和锻炼强度对葡萄糖控制机制的影响：a）肝葡萄糖的产生； b）骨骼肌中的异位脂肪分布和量，c）线粒体功能障碍 - 通过在IVGTT和OGTT期间，通过葡萄糖和非酯化脂肪酸动力学的决定因素对葡萄糖和非酯化脂肪酸动力学的决定因素进行肌肉活检样品进行评估。公共卫生相关性：这是一项针对人类受试者的运动研究，正在发展糖尿病的道路上，解决了三个问题。首先，与临床生活方式计划（包括饮食和专门的体重减轻）相比，仅锻炼计划如何比较？其次，是一个步行计划，还有很多，比慢跑计划好还是更好？第三，锻炼引起的福利如何产生？这些问题的答案应影响糖尿病的预防和治疗。