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

骨骼肌健康对不良生活方式相关的 2 型糖尿病和心血管疾病风险的影响

• 批准号: 10475714
• 负责人: Ryan A Harris
• 金额: $ 62.93万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10475714
• 关键词: Adipocytes; Affect; African American population; Age; American; Animals; Biological Markers; Blood Circulation; Blood Vessels; Body fat; Cardiovascular Diseases; Characteristics; Chronic Disease; Critical Illness; Data; Detection; Development; Endothelium; Environment; Environmental Impact; Environmental Risk Factor; Ethnic Origin; European; Evaluation; Exercise; Experimental Designs; Exposure to; Failure; Fatty acid glycerol esters; Fibrinogen; Gender; Genetic; Habits; Half-Life; Health; High Prevalence; Homeostasis; Human; Hypertension; Impairment; Individual; Infiltration; Insulin Resistance; Knowledge; Life Style; Link; Measurement; Measures; Mediating; Metabolic; Metabolic dysfunction; Mitochondria; Modeling; Molecular; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Pathway interactions; Pattern; Peptides; Physical activity; Play; Population Study; Prevention strategy; Psychosocial Stress; Risk; Role; Sampling; Shapes; Skeletal Muscle; Testing; Time; Tissues; Transducers; Twin Multiple Birth; Twin Studies; Unhealthy Diet; Vascular Diseases; Vascular Endothelium; Visit; arterial stiffness; behavior change; biobehavior; cardiovascular disorder risk; cardiovascular risk factor; carotid intima-media thickness; cytokine; energy balance; follow-up; gene environment interaction; health disparity; improved; insulin sensitivity; lifestyle factors; multi-ethnic; muscle form; muscle strength; obesogenic; physical inactivity; pre-clinical; preclinical development; preservation; response; success; treatment strategy; unhealthy lifestyle; vibration; weight loss program

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.

项目摘要 基于人群的研究传统上侧重于体脂(即肥胖)的测量，以评估 不良生活方式对胰岛素抵抗和心血管风险的贡献。虽然较少人认识到的是 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的基础上，该模型结合了多个 骨骼肌健康状况的维度评估(即质量、功能、力量和肌间脂肪渗透) 及其分子转导(即肌肉因子对全身振动的反应)，这是这一研究的基本目标 建议评估骨骼肌健康在调节肥胖因素作用中的系统贡献 生活方式(即心理社会压力、不健康饮食和缺乏体力活动)对胰岛素抵抗和 心血管疾病(CVD)临床前标志物(如动脉僵硬、颈动脉内膜中层)的发展 厚度和内皮功能)。评价环境因素对血吸虫病表现的影响 生物标记、遗传影响必须加以控制。以我们的佐治亚州双胞胎研究为基础 评估了532对非洲裔美国人数量大致相同的多种族双胞胎样本 和欧洲裔美国人(EA)在15年内4次，有体力活动和心理社会压力 在这些访问中收集到的，我们将进行一次额外的后续访问(年龄范围为22-45岁)，以衡量 骨骼肌健康、胰岛素抵抗和心血管疾病的临床前标记物。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、缺乏体力活动和不健康饮食) 会共同或明显地损害骨骼肌健康，而骨骼肌健康受损将是途径 肥胖生活方式因素对胰岛素抵抗和高血压病临床前标志物的影响 心血管疾病。(2)肌细胞因子对全身振动的反应可能是分子转导分子介导的。 骨骼肌健康对胰岛素抵抗和心血管疾病临床前标志物的影响。(3)种族和性别可 修改肥胖生活方式因素对目标1和目标2的影响。次要目标是：(1)检查 骨骼肌的健康状况能否解释AAs和EAs之间在2型风险方面的健康差异 糖尿病和心血管疾病。(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。这一提议代表了一种范式的转变，它将重点放在 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，但也有可能产生针对危重患者的新治疗策略 骨骼肌作为生存决定因素的疾病。此外，增加了对 促进AAS和EAS之间健康差距的机制将有助于发展种族-- 具体的预防策略。

项目成果

Epidemiology of accelerometer-based sleep parameters in US school-aged children and adults: NHANES 2011-2014.

• DOI: 10.1038/s41598-022-11848-8
• 发表时间: 2022-05-10
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Su, Shaoyong;Li, Xinyue;Xu, Yanyan;McCall, William V.;Wang, Xiaoling
• 通讯作者: Wang, Xiaoling

Blunted Rest-Activity Circadian Rhythm Is Associated With Increased Rate of Biological Aging: An Analysis of NHANES 2011-2014.

休息活动昼夜节律迟钝与生物衰老速度加快有关：NHANES 2011-2014 分析。

• DOI: 10.1093/gerona/glac199
• 发表时间: 2023
• 期刊: The journals of gerontology. Series A, Biological sciences and medical sciences
• 作者: Xu,Yanyan;Wang,Xiaoling;Belsky,DanielW;McCall,WilliamV;Liu,Yutao;Su,Shaoyong
• 通讯作者: Su,Shaoyong

Evidence of increased cardiovascular disease risk in left-handed individuals.

• DOI: 10.3389/fcvm.2023.1326686
• 发表时间: 2023
• 期刊: FRONTIERS IN CARDIOVASCULAR MEDICINE
• 影响因子: 3.6
• 作者: Simon, Abigayle B.;Norland, Kimberly;Blackburn, Marsha;Zhao, Sumang;Wang, Xiaoling;Harris, Ryan A.
• 通讯作者: Harris, Ryan A.

Sleep Variability, Sleep Irregularity, and Nighttime Blood Pressure Dipping.

睡眠变异、睡眠不规律和夜间血压下降。

• DOI: 10.1161/hypertensionaha.123.21497
• 发表时间: 2023
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Xu,Yanyan;Barnes,VernonA;Harris,RyanA;Altvater,Michelle;Williams,Celestine;Norland,Kimberly;Looney,Jacob;Crandall,Reva;Su,Shaoyong;Wang,Xiaoling
• 通讯作者: Wang,Xiaoling

Ethnic differences and heritability of blood pressure circadian rhythm in African and European American youth and young adults.

• DOI: 10.1097/hjh.0000000000002988
• 发表时间: 2022-01-01
• 期刊: Journal of hypertension
• 影响因子: 4.9
• 作者: Xu Y;Su S;Brown M;Snieder H;Harshfield G;Wang X
• 通讯作者: Wang X