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）：具有里程碑意义的糖尿病预防计划 (DPP) 建立了预防糖尿病前期患者 2 型糖尿病 (T2DM) 的“黄金标准”疗法，即生活方式的改变，包括饮食、锻炼和减肥。尽管这项研究在预防 T2DM 方面取得了进展，但仍然存在以下重要问题：1）锻炼计划带来的效果有多少？ 2）糖尿病前期患者的最佳/最小运动量和运动强度是多少； 3) 运动训练对于预防糖尿病前期受试者进展为 T2DM 的具体生理益处可能是什么？使用受控、随机设计，我们建议比较三个为期六个月的运动训练计划（涉及不同运动量和强度）对糖尿病前期患者血糖控制措施和机制的影响，并评估这三种运动的总体有效性。仅通过将其与包含 DPP 组成部分的六个月临床生活方式干预 (CLI) 进行比较，但持续时间要短得多。研究人群将包括空腹血糖受损的前驱糖尿病患者（IFG-空腹血糖100-125 mg/dl），伴或不伴糖耐量受损-IGT。所有受试者将被随机分配到以下运动训练或生活方式干预组之一，为期六个月：1) 低剂量/中等强度：每周 150 分钟中等强度运动，2) 高剂量/中等强度：300 分钟分钟/周的中等强度运动，3) 高剂量/剧烈强度：200 分钟/周的剧烈强度运动（热量等于高剂量、即上述第 2 组），4）临床生活方式干预（饮食、运动和减肥）：每周 150 分钟的中等强度运动（与第 1 组相同）加饮食，以及 6% 的减肥目标。目标 1. 确定仅运动干预措施对血糖控制指标（空腹血糖、口服葡萄糖耐量和胰岛素敏感性）的不同数量和强度的有效性。目标 2. 确定不同运动量和强度对重要的继发性糖尿病和心脏代谢危险因素的影响。目标 3. 确定不同运动量和强度对血糖控制机制的影响：a) 肝葡萄糖生成； b) 异位脂肪分布和数量，c) 骨骼肌线粒体功能障碍 - 通过股外侧肌活检样本的代谢组学性能进行评估 d) IVGTT 和 OGTT 期间葡萄糖和非酯化脂肪酸动力学的决定因素。公共健康相关性：这是一项针对人类受试者的运动研究，探讨发展为糖尿病的途径，解决了三个问题。首先，与包括饮食和专门减肥的临床生活方式计划相比，单独的运动计划如何比较？其次，步行计划（以及很多步行计划）是否与慢跑计划一样好或更好？第三，运动带来的好处如何产生？这些问题的答案应该会对糖尿病的预防和治疗产生影响。