Lean Body Mass and the Development of Diabetes

 描述（由申请人提供）：鉴于未来糖尿病的预计负担将增加，了解其发展的可改变风险因素对于公共卫生至关重要，以便制定适当和有针对性的预防策略。虽然已经很好地描述了肥胖是2型糖尿病发展的危险因素，但关于身体成分和糖尿病之间关系的关键问题仍然没有答案，特别是考虑到将体重指数（BMI）与糖尿病联系起来的研究仅部分解决了身体成分的作用，并且BMI也可能受到肌肉质量的影响。更具体地说：1）瘦体重（肌肉）随时间的变化，特别是瘦体重的下降，与糖尿病发病风险有何关系？2)老年人瘦体重变化与糖尿病发展的关系比年轻人强吗？3)是否存在瘦体重与血糖水平升高的双向影响，这可能表明下降的恶性循环？我们建议使用复杂的，最先进的，统计方法来探讨这些问题，在正在进行的巴尔的摩老龄化纵向研究（BLSA），一个队列的社区居住的个人与广泛的后续行动超过50年。结果数据的质量、血糖评估的频率和BLSA随访的持续时间是无与伦比的。我们提出的研究有以下目的：目的1：描述瘦体重随时间变化的特定模式（使用双能X射线吸收测定法）与糖尿病发展相关的程度，占总脂肪量的变化，使用创新的潜在类别分析方法。在第二个目标中，我们将探讨瘦体重变化与糖尿病风险之间的关系在老年人与年轻人之间的差异程度。目标二：在考虑了全身脂肪的变化后，描述瘦体重和血糖水平升高（血糖异常）之间的动态双向关联。我们将使用领先滞后结构方程模型，一种新的统计技术，特别适合于这一目的，以提供进一步的见解。这些分析有两个重要目的。首先，这将是第一个纵向数据，以证明瘦体重的不良变化与糖尿病发病率的关系，以完善针对糖尿病新预防策略的临床试验的人群。其次，描述瘦体重和功能障碍的潜在双向关系可以为血糖升高的临床管理提供信息，特别是在功能下降的高风险人群中。这项研究肯定应该回答可以用观测数据回答的相关问题，并且对于推动该领域的发展至关重要。研究瘦体重变化与糖尿病发展的关系对于开发新的预防策略至关重要，这些策略可以减少这种疾病及其并发症的负担。

 DESCRIPTION (provided by applicant): Given the projected increasing burden of diabetes in the future, understanding modifiable risk factors for its development is important for public health in order to develop appropriate and targeted preventive strategies. While it has been well described that obesity is a risk factor for type 2 diabetes development, critical questions regarding the relationship of body composition and diabetes remain unanswered, particularly given that research linking body-mass index (BMI) to diabetes only partially addresses the role of body composition and that BMI may also be influenced by muscle mass. More specifically: 1) How do changes in lean body (muscle) mass over time, particularly declines in lean body mass, relate to the risk of incident diabetes?; 2) Is the relationship of lean body mass changes to the development of diabetes stronger in older versus younger ages?; 3) Are there bidirectional influences of lean body mass with elevated glucose levels that may suggest a vicious cycle of decline? We propose to use complex, state-of-the art, statistical methodology to explore these questions in the ongoing Baltimore Longitudinal Study of Aging (BLSA), a cohort of community-dwelling individuals with extensive follow-up of over fifty years. The quality of the outcomes data, the frequency of glycemic assessments, and the duration of follow-up in BLSA are unparalleled. Our proposed study has the following aims: Aim 1: To describe the degree to which specific patterns of change in lean body mass over time (using dual-energy X-ray absorptiometry) are related to the development of diabetes, accounting for changes in total fat mass, using innovative latent class analytic methodology. In a Secondary Aim, we will explore the degree to which the relationship of lean body mass changes to the risk of diabetes differs in older versus younger age. Aim 2: To characterize the dynamic, bidirectional association between lean body mass and elevated glucose levels (dysglycemia) after accounting for changes in total body fat. We will use lead-lag structural equation modeling, a novel statistical technique that is particularly well suited for this purpose, to provide further insights. These analyses will serve two important purposes. First, this will be the first longitudinal data to demonstrate a relationship of adverse changes in lean body mass to incident diabetes, in order to refine the population for a clinical trial targeting novel prevention strategies for diabetes. Second, characterizing the potential bidirectional relationships of lean body mass and dysglycemia can inform the clinical management of elevated blood glucoses, particularly in those at high-risk for functional decline. This research should definitely answer the relevant questions that can be answered with observational data and are essential to move the field forward. Investigating the relationship of lean body mass changes to the development of diabetes is critically important to develop novel preventive strategies that can reduce the burden of this disease and its complications in the future.