Lean Body Mass and the Development of Diabetes

 描述(由申请人提供)：鉴于预计未来糖尿病的负担将日益加重，了解其发展的可改变的风险因素对公共卫生非常重要，以便制定适当和有针对性的预防策略。虽然肥胖是2型糖尿病发展的危险因素，但有关身体成分和糖尿病关系的关键问题仍然没有得到回答，特别是考虑到将身体质量指数(BMI)与糖尿病联系起来的研究只部分解决了身体成分的作用，而且BMI也可能受到肌肉质量的影响。更具体地说：1)随着时间的推移，瘦身体(肌肉)质量的变化，特别是瘦身体质量的下降，与发生糖尿病的风险有什么关系？2)瘦身体质量变化与糖尿病发展的关系在年龄较大的人和较年轻的人中是否更强？3)瘦身体质量与血糖水平升高是否存在双向影响，这可能意味着恶性循环的下降？我们建议使用复杂的、最先进的统计方法来探索正在进行的巴尔的摩老龄化纵向研究(BLSA)中的这些问题，这是一组居住在社区的个人，经过50多年的广泛跟踪调查。在BLSA中，结果数据的质量、血糖评估的频率和随访时间都是无与伦比的。我们提出的研究有以下目标：目标1：使用创新的潜在分类分析方法，描述特定的瘦体重随时间的变化模式(使用双能X射线吸收法)与糖尿病的发展相关的程度，以说明总脂肪质量的变化。在第二个目标中，我们将探索瘦体重变化与糖尿病风险的关系在年龄较大和较年轻时的不同程度。目的2：在考虑了体内总脂肪的变化后，描述瘦体重和血糖升高(血糖异常)之间的动态、双向关联。我们将使用领先-滞后结构方程建模，这是一种特别适合于这一目的的新统计技术，以提供进一步的见解。这些分析将服务于两个重要目的。首先，这将是第一个证明瘦体重的不利变化与糖尿病发病的关系的纵向数据，以便为针对糖尿病的新预防策略的临床试验完善人群。其次，明确瘦体重和血糖异常的潜在双向关系可以为临床治疗血糖升高提供信息，特别是在那些功能下降的高危人群中。这项研究应该明确回答可以用观测数据回答的相关问题，这些问题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以减轻糖尿病及其并发症的负担至关重要。

 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.