MASS: Muscle and disease in postmenopausal women

摘要 骨质疏松症(低肌肉质量)和糖尿病是两种非常普遍的、使人致残的慢性健康疾病 影响到年长女性。有新的证据表明，糖尿病和受损的胰岛素-葡萄糖稳态 可能会加速与年龄相关的肌肉质量的丧失。检查可更改的风险因素至关重要。 (例如，肌肉质量、血糖异常)，导致功能障碍、跌倒和骨折的风险(3F) 上了年纪的人。我们的研究将解决一个关键的知识缺口：胰岛素-葡萄糖稳态在多大程度上 与老年女性肌肉质量随时间的减少有关，以及这是否因种族/民族而异。 此外，这项研究还将研究受损的胰岛素-葡萄糖稳态和糖耐量下降之间的反馈回路。 骨骼肌块。直到最近，在大规模的肌力衰竭研究中，完全描述肌肉质量变化的能力 社区居住的老年人一直受到与肌肉测量相关的挑战的限制 质量。这是取得进展的关键障碍。该项目将使用一种新颖的在家远程样品采集 方案(D3Cr法)和指刺采血试剂盒检测肌块纵向变化 来自妇女健康倡议(WHI)的3177名绝经后妇女的胰岛素-葡萄糖稳态。 WHI是一项对绝经后妇女进行的大型前瞻性队列研究，随访时间为30年。 研究参与者将来自WHI的一个子队列，即长寿研究2(LLS2)，这是一个不同的老年人队列 妇女(56%来自种族/少数民族群体；平均年龄85岁)。这项研究的目的是：1)提供见解 研究绝经后妇女D3Cr肌质量随年龄变化的纵向模式，以及她们的 根据种族/民族、糖尿病状况和血糖水平，功能衰退的风险增加 对照，2)检查胰岛素-葡萄糖稳态受损和 D3Cr-肌肉质量使用高级统计方法，3)使用机器学习方法开发 多变量风险分层算法，包括D3Cr-肌肉质量、胰岛素-血糖受损指数 动态平衡和功能能力的客观测量(握力、步速)，以识别 绝经后妇女在这3个F中风险最高。该项目解决了由 NIA，用于老年科学研究，包括确定衰老过程和 与年龄相关的变化背后的机制。在未来，这些结果将被用于开发干预措施 旨在减轻骨质疏松症和糖尿病的有害影响，并促进绝经后的健康衰老 妇女，包括来自通常在健康方面代表性不足的种族/少数民族群体的妇女 研究。

ABSTRACT Sarcopenia (low muscle mass) and diabetes are two highly prevalent and disabling chronic health conditions affecting older women. There is emerging evidence that diabetes and impaired insulin-glucose homeostasis may accelerate age-related loss of muscle mass. It is critically important to examine modifiable risk factors (e.g., muscle mass, dysglycemia) that contribute to risk of functional impairment, falls and fractures (the 3Fs) in older adults. Our study will address a key knowledge gap: the extent to which insulin-glucose homeostasis is associated with loss of muscle mass over time in aging women and whether this varies by race/ethnicity. Moreover, this study will examine the feedback loop between impaired insulin-glucose homeostasis and loss of skeletal muscle mass. Until recently, the ability to fully characterize change in muscle mass in large studies of community dwelling older adults has been limited by challenges associated with obtaining measures of muscle mass. This is a critical barrier to progress. This project will use a novel at-home remote sample collection protocol (D3Cr method) and finger-prick blood collection kit to examine longitudinal change in muscle mass and insulin-glucose homeostasis in 3177 postmenopausal women from the Women’s Health Initiative (WHI). The WHI is a large, ongoing prospective cohort study of postmenopausal women with 30 years of follow-up. Study participants will be drawn from a WHI sub-cohort, the Long Life Study 2 (LLS2), a diverse cohort of older women (56% from racial/ethnic minority groups; mean age 85 years). The study aims are to: 1) provide insight into longitudinal patterns of change in D3Cr-muscle mass in postmenopausal women as they age, and their risk for functional decline increases, by race/ethnicity, diabetes status, and according to level of glycemic control, 2) examine the cyclical relationship between impaired insulin-glucose homeostasis and change in D3Cr-muscle mass using advanced statistical approaches, and 3) use machine learning methods to develop multivariate risk stratification algorithms, including D3Cr-muscle mass, indices of impaired insulin-glucose homeostasis, and objective measures of functional capacity (grip strength, gait speed), to identify postmenopausal women at highest risk of the 3 Fs. This project addresses an urgent need identified by the NIA for research on geroscience, including research that determines the rate of aging processes and mechanisms underlying age-related change. In the future, these results will be used to develop interventions designed to mitigate harmful effects of sarcopenia and diabetes and promote healthy aging in postmenopausal women, including women from racial/ethnic minority groups that are typically underrepresented in health research.