MASS: Muscle and disease in postmenopausal women

摘要 肌肉减少症（低肌肉质量）和糖尿病是两种高度流行和致残的慢性健康状况 影响老年妇女。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损失。检查可改变的风险因素至关重要 (e.g.,肌肉质量，功能障碍），导致功能障碍，福尔斯和骨折（3F）的风险， 老年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是 与老年女性随时间推移肌肉质量损失相关，以及这是否因种族/民族而异。 此外，本研究还将探讨胰岛素-葡萄糖稳态受损和胰岛素分泌减少之间的反馈回路。 骨骼肌质量直到最近，在大型研究中完全描述肌肉质量变化的能力， 社区居住的老年人受到与获得肌肉测量相关的挑战的限制， 马萨诸塞州这是取得进展的一个关键障碍。该项目将使用一种新颖的在家远程样本收集 方案（D3 Cr方法）和手指采血试剂盒检查肌肉质量的纵向变化 和胰岛素-葡萄糖稳态在3177绝经后妇女的妇女健康倡议（WHI）。 WHI是一项针对绝经后妇女的大型、持续前瞻性队列研究，随访30年。 研究参与者将从WHI子队列，长寿研究2（LLS 2），一个老年人的多样化队列， 妇女（56%来自少数种族/族裔群体;平均年龄85岁）。本研究的目的是：1）提供洞察力 绝经后妇女随着年龄的增长，D3 Cr-肌肉质量的纵向变化模式， 根据人种/种族、糖尿病状态和血糖水平，功能下降的风险增加 对照组，2）检查受损的胰岛素-葡萄糖稳态与胰岛素水平变化之间的周期性关系。 D3 Cr-肌肉质量使用先进的统计方法，和3）使用机器学习方法来开发 多变量风险分层算法，包括D3 Cr-肌肉质量、胰岛素-葡萄糖受损指数 稳态和功能能力的客观测量（握力，步态速度），以确定 绝经后妇女在3个F中的风险最高。该项目解决了联合国难民事务高级专员办事处确定的一项迫切需要， NIA用于老年科学研究，包括确定衰老过程速度的研究， 与年龄相关的变化的机制。未来，这些结果将用于制定干预措施 旨在减轻肌肉减少症和糖尿病的有害影响，促进绝经后健康衰老 妇女，包括在卫生部门代表性通常不足的少数种族/族裔群体的妇女 research.

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.