Hyperglycemia, Frailty and Disability in Older Women

描述（由申请人提供）：随着残疾越来越被认为是糖尿病的主要临床和公共卫生后果，糖尿病如何导致残疾变得不太清楚。本研究的目的是调查高血糖本身是否与行动能力、耐力、力量和日常生活活动障碍有独立的联系。我们将验证高血糖有助于衰弱（最近在社区居住的老年人中普遍存在的一种易受压力因素影响的综合征）的发展，并通过涉及炎症介质的途径导致残疾的假设。具体目的是：1)描述由糖蛋白测量的高血糖水平随时间的变化；2)评估高血糖与炎症介质的关联，以及肥胖如何改变这种关联；3、评估高血糖与定义虚弱的特征（体重减轻、虚弱、行动迟缓、疲惫、低运动耐量）和虚弱综合征本身的关联，以确定基线高血糖或其随时间的变化是否预测虚弱的发生或进展；4、评估高血糖对通过虚弱来衡量残疾的贡献，并对合并症进行总体调整；5、寻找从高血糖到残疾通路中可能适合干预的潜在临界点的证据，例如(a)高血糖阈值水平；(b)高血糖可能特别成问题的老年人亚群，例如患有血管疾病和肥胖的老年人；6、评估高血糖衰弱途径导致的衰弱和残疾的人群归因风险。我们的研究策略包括：使用两项补充性研究，即妇女健康与老龄化研究I和II，对功能和残疾妇女进行研究，这两项研究对相关变量的测量几乎相同；以及横断面和纵向数据分析。分析将集中于纵向变化模型，包括随机效应增长曲线、随机效应变化模型和时间到事件模型。本研究将把糖尿病的炎症破坏与虚弱和残疾联系起来，帮助确定高血糖对老年人重要的不良健康结果的潜在影响，并为未来老年糖尿病患者血糖控制的观察性和介入性研究提供重要的初步数据。

DESCRIPTION (provided by applicant): As disability becomes increasingly recognized as a diabetes outcome of major clinical and public health importance, it becomes less clear how diabetes causes disability. The goal of the proposed research is to investigate whether hyperglycemia itself has an independent association with disability in mobility, endurance, strength and activities of daily living. We will test the hypothesis that hyperglycemia contributes to the development of frailty (a syndrome of vulnerability to stressors recently shown to be prevalent in community-dwelling older adults) and through this to disability, via a pathway involving inflammatory mediators. The specific aims are: l) to describe change over time in level of hyperglycemia measured by glycohemoglobin; 2) to evaluate associations of hyperglycemia with inflammatory mediators and how that association is modified by obesity; 3, to evaluate associations of hyperglycemia with characteristics defining frailty (weight loss, weakness, slowness, exhaustion, low exercise tolerance) and the frailty syndrome itself, to determine if hyperglycemia at baseline or its change over time predicts onset or progression of frailty; 4, to evaluate the contribution of hyperglycemia to measures of disability through frailty, and overall, adjusting for comorbidity; 5, to seek evidence for potential critical points in the pathway from hyperglycemia to disability that might be amenable to intervention, such as (a) threshold levels of hyperglycemia; (b) subsets of older people in whom hyperglycemia may be particularly problematic such as those with vascular conditions and obesity; and 6, to evaluate population attributable risk of frailty and disability due to the hyperglycemia frailty pathway. Our research strategy includes: study of women who are both functional and disabled using two complementary studies, the Women's Health and Aging Studies I and II, which have nearly identical measures of relevant variables; and cross sectional and longitudinal data analysis. Analyses will focus on longitudinal change models including random effect growth curves, random-effect change models, and time to event models. This research will link inflammatory disruption in diabetes to that of frailty and disability, help determine the potential impact of hyperglycemia on adverse health outcomes important to older adults, and provide important preliminary data for future studies, observational and interventional, of glycemic control in older adults with diabetes.