Role of Skeletal Muscle Health on Poor LIfestyle Related Type 2 Diabetes and Cardiovascular Disease Risk

项目摘要 基于人群的研究传统上集中于测量身体脂肪（即肥胖），以评估 不良生活方式对胰岛素抵抗和心血管风险的贡献。虽然很少有人认识到， 骨骼肌在这些情况下的作用。建立在我们提出的生物行为模型，其中包括多- 骨骼肌健康的维度评价（即质量、功能、强度和肌间脂肪浸润） 及其分子换能器（即肌因子对全身振动的反应），这一研究的基本目的是 一项建议是评估骨骼肌健康在介导肥胖的作用中的全身贡献。 生活方式（即心理社会压力、不健康饮食和缺乏运动）对胰岛素抵抗和 心血管疾病（CVD）临床前标志物（即动脉僵硬度、颈动脉内膜中层）的发展 厚度和内皮功能）。评价环境因素对肺结核表现的影响， 生物标记、遗传影响必须加以控制。基于我们的格鲁吉亚CV双胞胎研究， 评估了532对双胞胎的多种族双胞胎样本，其中非洲裔美国人（AA）的数量大致相等 和欧洲裔美国人（EA）4次超过15年，并有身体活动和心理社会压力 在这些访视期间收集的数据，我们将进行一次额外的随访访视（年龄范围22-45岁），以测量 骨骼肌健康、胰岛素抵抗和CVD的临床前标志物。具体目标是测试 假设：（1）肥胖的生活方式因素（即心理社会压力，身体活动不足和不健康的饮食） 将共同或明显损害骨骼肌健康，而受损的骨骼肌健康将是 肥胖生活方式因素通过这些途径影响胰岛素抵抗和胰岛素抵抗的临床前标志物， CVD。(2)肌因子对全身振动的反应将是介导振动效应的分子换能器。 骨骼肌健康对胰岛素抵抗和CVD临床前标志物的影响。(3)种族和性别可能 改变致肥胖生活方式因素对目标1和2的影响。第二个目的是：（1）检查 骨骼肌健康是否可以解释AA和EA在2型糖尿病风险方面的健康差异 糖尿病和CVD。(2)研究基因-环境相互作用对骨骼肌的潜在影响 对肥胖生活方式的反应。这一建议代表了一种范式转变， 骨骼肌而不是肥胖是不良生活方式引起的代谢和血管功能障碍的原因。 这些信息不仅可以指导知识的有效传播，提高成功率 行为改变，但也有可能产生新的治疗策略，针对关键的 骨骼肌作为生存决定因素的疾病。此外，还增加了对 导致AA和EA之间健康差异的机制将使种族的发展成为可能- 具体的预防策略。

Project Summary Population-based studies have traditionally focused on measurement of body fat (i.e. obesity) to assess the contribution of poor lifestyles to insulin resistance and cardiovascular risk. While much less recognized is the role of skeletal muscle in these conditions. Built on our proposed biobehavioral model which incorporates multi- dimensional evaluation of skeletal muscle health (i.e. mass, function, strength, and intermuscular fat infiltration) and its molecular transducer (i.e. myokine response to whole body vibration), the fundamental objective of this proposal is to evaluate the systemic contribution of skeletal muscle health in mediating the role of obesogenic lifestyles (i.e. psychosocial stress, unhealthy diet and physical inactivity) on insulin resistance and the development of preclinical markers of cardiovascular disease (CVD) (i.e. arterial stiffness, carotid intima media thickness and endothelial function). To evaluate the impact of environmental factors on manifestation of biological markers, genetic influences must be controlled. Building on our Georgia CV Twin Study which has evaluated a multi-ethnic twin samples of 532 twin pairs with roughly equal number of African Americans (AA) and European Americans (EA) 4 times over 15 years and has physical activity and psychosocial stress collected during these visits, we will conduct one additional follow-up visit (age range 22-45 yrs) to measure skeletal muscle health, insulin resistance and preclinical markers of CVD. The specific aims are to test the hypotheses that: (1) Obesogenic lifestyle factors (i.e. psychosocial stress, physical inactivity and unhealthy diet) will jointly or distinctively impair skeletal muscle health, and impaired skeletal muscle health will be the pathway through which obesogenic lifestyle factors exert their influence on insulin resistance and preclinical markers of CVD. (2) Myokine response to whole body vibration will be the molecular transducers mediating the effect of skeletal muscle health on insulin resistance and preclinical markers of CVD. (3) Ethnicity and gender may modify the influence of obesogenic lifestyle factors upon aim 1 and 2. The secondary aims are: (1) To examine whether skeletal muscle health can explain the health disparity between AAs and EAs in the risk of type 2 diabetes and CVD. (2) To examine the potential effects of gene-environment interactions on skeletal muscle response to obesogenic lifestyles. This proposal represents a paradigm shift by focusing on impairments in skeletal muscle rather than adiposity as a cause of poor lifestyle induced metabolic and vascular dysfunction. This information can not only guide the effective dissemination of the knowledge and increase the success rate of behavior changes, but also has the potential to generate new treatment strategies targeting the critical illness in which skeletal muscle as a determinant of survival. Furthermore, increased understanding of the mechanisms contributing to health disparities between AAs and EAs will enable the development of ethnicity- specific prevention strategies.