Muscle Mass and Evolution of Diabetes Risk: Longitudinal Analysis

肌肉质量和糖尿病风险的演变：纵向分析

• 批准号: 9250766
• 负责人: Arun S Karlamangla
• 金额: $ 19.25万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9250766
• 关键词: Aging; Behavioral; Biolectric Impedance; Biological; Biological Markers; Blood Vessels; Body Composition; Body Water; Body fat; C-reactive protein; Clinical; Clinical Trials; Complications of Diabetes Mellitus; Data; Data Analyses; Development; Diabetes Mellitus; Dual-Energy X-Ray Absorptiometry; Epidemic; Ethnic Origin; Etiology; Evolution; Exercise; Exercise stress test; Fatty acid glycerol esters; Feedback; Functional disorder; Future; Glucose Intolerance; Guidelines; Incidence; Individual; Infiltration; Inflammation; Insulin Resistance; Knowledge; Lead; Life Style; Lipids; Measurement; Measures; Mediating; Medical; Menopause; Metabolic; Monitor; Muscle; Muscular Atrophy; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Physiological; Physiology; Play; Prevention; Prospective cohort; Public Health; Race; Recommendation; Research; Resources; Role; Sampling; Scanning; Serum; Study of Women' s Health Across the Nation; Technology; Testing; Time; Woman; Work; base; clinical application; cohort; combat; cost; diabetes risk; diabetic; exercise prescription; exercise regimen; fat burning; glucose metabolism; knowledge base; longitudinal analysis; longitudinal dataset; muscle form; portability; prevent; prospective; psychosocial; public health relevance; racial difference; reduced muscle mass; sedentary lifestyle

 DESCRIPTION (provided by applicant): The incidence of type 2 diabetes mellitus has been rising worldwide, and its associated costs are growing rapidly. It is therefore imperative that all major factors that contribute to the development of diabetes are identified. While the causal role of adiposity in the development of insulin resistance (the pathophysiology underlying type 2 diabetes) has long been recognized, there is increasing observational evidence that low muscle mass also contributes independently to poor glucose metabolism. This secondary data analysis R21 application proposes to quantify the independent influences of fat and muscle mass in the development of insulin resistance and dysglycemia, using prospective cohort data over 15 waves (and 20 years) from a large, well-characterized, cohort of women transitioning through the menopause, a transition often accompanied by substantial increase in glucose intolerance and fat mass, and decrease in muscle mass. To date, nearly all large studies of muscle mass and dysglycemia have been cross-sectional and have not established a causal role for low muscle mass in the development of diabetes. The Study of Women's Health Across the Nation (SWAN), which annually collected a rich set of biological and medical data, as well as body composition from dual-energy X-ray absorptiometry (DXA) scans and bioelectrical impedance (BEI) measurements, represents a uniquely valuable resource with which to tease apart the independent contributions of fat mass and muscle mass to the development of type 2 diabetes. This project will leverage the large changes in glucose metabolism and body composition over the 15 waves (baseline plus 14 follow ups) in this cohort and the variability in their magnitude and timing across the sample to identify the causal effects of fat and muscle mass on insulin resistance and dysglycemia, and separate out the reverse causal effects of diabetes on muscle mass. The project specific aims are: 1) To quantify the independent contributions of decreasing muscle mass and increasing fat mass to longitudinal changes in glucose metabolism; 2) To compare the predictive ability of whole body muscle mass measured by DXA against that estimated by BEI to predict longitudinal changes in glucose metabolism; 3) To determine if overt diabetes is associated with greater decreases over time in muscle mass, and if this association is mediated by inflammation. This research will advance our understanding of a) the independent roles of fat and muscle mass in the development of diabetes risk; and b) the clinical applicability of the simpler, less expensive, easier to use, BEI based measurement of muscle mass. This work will inform the development and testing of the optimal exercise prescription that is both time-efficient and most effective in preventing diabetes and ultimately influence clinical guidelines and public health recommendations aimed at combating the global diabetes epidemic.

 描述（由申请人提供）：2型糖尿病的发病率在全球范围内一直在上升，其相关费用也在迅速增长。因此，当务之急是， 确定了导致糖尿病发展的主要因素。虽然肥胖在胰岛素抵抗（2型糖尿病的病理生理学基础）发展中的因果作用早已被认识到，但越来越多的观察证据表明，低肌肉质量也独立地导致葡萄糖代谢不良。该二次数据分析R21应用程序建议量化脂肪和肌肉质量在胰岛素抵抗和功能障碍发展中的独立影响，使用来自一个大型的、充分表征的绝经期女性队列的15个波（和20年）的前瞻性队列数据，绝经期的过渡通常伴随着葡萄糖耐受不良和脂肪质量的大幅增加以及肌肉质量的减少。 到目前为止，几乎所有关于肌肉质量和功能障碍的大型研究都是横断面的，并且还没有建立低肌肉质量在糖尿病发展中的因果关系。全国妇女健康研究（SWAN）每年收集一组丰富的生物和医学数据，以及来自双能X射线吸收测定法（DXA）扫描和生物电阻抗（BEI）测量的身体成分，代表了一种独特的有价值的资源，可以梳理脂肪量和肌肉量对2型糖尿病发展的独立贡献。该项目将利用该队列中葡萄糖代谢和身体成分在15个波（基线加14个随访）中的巨大变化以及样本中其幅度和时间的可变性，以确定脂肪和肌肉质量对胰岛素抵抗和功能障碍的因果影响，并分离出糖尿病对肌肉质量的反向因果影响。该项目的具体目标是：1）量化肌肉质量减少和脂肪质量增加对葡萄糖代谢纵向变化的独立贡献：2）比较DXA测量的全身肌肉质量与BEI估计的全身肌肉质量预测葡萄糖代谢纵向变化的能力; 3）确定显性糖尿病是否与肌肉质量随时间的推移而大幅下降相关，以及这种关联是否由炎症介导。 这项研究将推动我们的 理解a）脂肪和肌肉质量在糖尿病风险发展中的独立作用;和B）更简单、更便宜、更容易使用的基于BEI的肌肉质量测量的临床适用性。这项工作将为最佳运动处方的开发和测试提供信息，这些运动处方在预防糖尿病方面既省时又最有效，并最终影响旨在对抗全球糖尿病流行的临床指南和公共卫生建议。