Epidemiology of Precursors to Type 2 Diabetes

描述（由申请人提供）：2型糖尿病（T2D）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的行为和社会因素的迅速增加，导致了美国T2D发病率的上升及其差异。拟议的研究重点是糖尿病前期，已知干预可以预防T2D，并且怀疑T2D的下游种族差异开始。前驱糖尿病的表型种族差异已被确定，但遗传差异尚未确定。研究T2D遗传风险的种族差异有很强的科学和伦理理由。这是面向患者的研究（K24）的中期职业研究者奖的更新。候选人James B. Meigs医学硕士，致力于以患者为导向的研究事业，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：在多种族人群样本（非裔美国人、西班牙裔、亚洲人和欧洲血统）中发现、绘制和表征T2D数量性状相关的遗传位点。这将通过分阶段的全基因组关联研究和荟萃分析来实现，并通过相互作用、结果、生理学、途径和测序研究来确定已证实的T2D数量性状位点。糖尿病相关的数量特征包括空腹胰岛素、葡萄糖和糖化血红蛋白水平；2. 将新的遗传知识转化为不同种族的样本，通过对基因测量和社会、行为、环境和生物生理测量的纵向和多层次测试，提高空腹血糖、前驱糖尿病或临床T2D的风险，为临床和人群健康带来益处；3. 在哈佛大学、麻省总医院的优越环境和广泛的研究合作网络中，确保在职业生涯中期为面向患者的研究项目开发提供保护时间，并通过保持持续的能力为更多的初级面向患者的研究人员提供指导，从而建立候选人成功的研究和指导计划。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。这个职业中期奖项申请旨在直接解决以患者为导向的研究和指导的需求，重点关注T2D的原因和后果。扩大对T2D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.