Epidemiology of Precursors to Type 2 Diabetes

描述（由申请人提供）：2型糖尿病（T2 D）是一个日益严重的健康问题，特别是在少数民族中。遗传背景的祖先变异，加上最近肥胖和不健康行为和社会因素的快速增加，导致美国T2 D发病率上升及其差异。拟议的研究重点是糖尿病前期，已知干预措施可预防T2 D，T2 D的下游种族种族差异被怀疑开始。糖尿病前期的表型种族-民族差异已被描述，但遗传差异还没有。研究T2 D遗传风险的种族-民族差异有很强的科学和伦理理由。这是在以患者为导向的研究（K24）的职业生涯中期研究者奖的更新。候选人詹姆斯B。Meigs MD MPH，致力于以患者为导向的研究生涯，研究2型糖尿病的病因和预防。该奖项将支持以下具体目标：1。在多种族人群样本（非裔美国人，西班牙裔，亚洲和欧洲血统）中发现，绘制和表征T2 D定量性状相关的遗传基因座。这将通过分阶段的全基因组关联研究与荟萃分析以及使用相互作用、结局、生理学、途径和测序研究对确认的T2 D数量性状基因座进行表征来实现。糖尿病相关的数量性状包括空腹胰岛素、葡萄糖和血红蛋白A1 c水平; 2.将新的遗传知识转化为不同的种族-民族样本，用于临床和人群健康益处，使用遗传测量的纵向和多级测试以及空腹血糖升高、前驱糖尿病或临床T2 D的风险的社会、行为、环境和生物生理学测量; 3.在候选人成功的研究和指导计划的基础上，确保在哈佛、马萨诸塞州总医院和广泛的研究合作网络的优越环境中，有受保护的职业生涯中期时间来开发以患者为导向的研究计划，并保持持续的能力，为大量以患者为导向的初级研究人员提供指导。以患者为导向的研究对于将科学知识转化为人口健康效益至关重要。T2是一个快速增长的临床和公共卫生问题。这个职业中期奖申请旨在直接解决以患者为导向的研究和指导的需要，重点是T2 D的原因和后果。扩大对T2 D前体的了解对于确定预防和控制日益扩大的糖尿病流行的新方法至关重要。

DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) is a growing health problem, especially in minority race-ethnic groups. Ancestral variation in genetic background coupled with recent, rapid increases in obesity and unhealthy behavioral and social factors account for rising rates of T2D and its disparities in the U.S. The proposed research focuses on prediabetes, where intervention is known to prevent T2D, and where downstream race-ethnic disparities in T2D are suspected to begin. Phenotypic race-ethnic differences in prediabetes have been characterized, but genetic differences have not. There are strong scientific as well as ethical reasons to study race-ethnic differences in T2D genetic risk. This is a renewal of a mid-career investigator award in patient-oriented research (K24). The candidate, James B. Meigs MD MPH, has devoted his patient-oriented research career to study of the cause and prevention of type 2 diabetes. This award will support the following Specific Aims: 1. Discover, map, and characterize T2D quantitative trait-associated genetic loci in multi-ethnic population samples (African American, Hispanic, Asian and European ancestry). This will be achieved using staged genome-wide association studies with meta-analysis and with characterization of confirmed T2D quantitative trait loci using interaction, outcomes, physiology, pathway, and sequencing studies. Diabetes-related quantitative traits include levels of fasting insulin, glucose, and hemoglobin A1c; 2. Translate new genetic knowledge to diverse race-ethnic samples for clinical and population health benefit using longitudinal and multilevel tests of genetic measures and social, behavioral, environmental and biophysiological measures of risk for elevated fasting glucose, prediabetes, or clinical T2D; 3. Build on the candidate's successful research and mentoring program by ensuring mid-career protected time for patient-oriented research program development within the superb environment of Harvard, Massachusetts General Hospital and an extensive network of research collaborations, and by maintaining the ongoing capacity to provide mentoring to a larger number of junior patient-oriented investigators. Patient-oriented research is critical for the translation of scientific knowledge into population health benefit. T2 is a rapidly growing clinical and public health problem. This mid-career award application seeks to directly address the need for patient-oriented research and mentoring focused on the causes and consequences of T2D. Expanded knowledge of precursors of T2D is critical to identify novel approaches for prevention and control of the widening diabetes epidemic.