Epidemiology of Precursors to Type 2 Diabetes

描述（由申请人提供）： 2型糖尿病是一个日益严重的健康问题。糖尿病的主要前兆包括肥胖和遗传易感性。糖尿病表型风险（“前驱糖尿病”）已通过临床研究进行了表征，但需要在作为预防和治疗的主要场所的卫生保健系统中进行更好的表征。这是一个职业生涯中期的研究者奖在以病人为导向的研究（K24）的建议。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。该奖项将支持以下广泛的具体目标： 1.通过对以下假设的检验，阐明肥胖和遗传风险在2型糖尿病发病机制中的作用：a）脂肪因子失调是肥胖导致2型糖尿病的联系; B）排列的和特定的候选单核苷酸多态性（SNP）与2型糖尿病和相关的数量性状相关; 2.通过以下假设的检验，将前驱糖尿病表型的流行病学知识转化为临床应用，以获得人群健康益处：a）由电子健康记录（EHR）中可用的替代标记物定义的前驱糖尿病具有代谢概况类似于临床和流行病学研究中严格定义的前驱糖尿病的代谢概况的表型; B）患有“EHR前驱糖尿病”的人的医疗保健利用和临床结果介于没有EHR前驱糖尿病的人和患有临床糖尿病的人之间，这表明识别这些人进行干预以降低风险的价值; 3.在候选人成功的研究和指导计划的基础上，确保职业生涯中期的保护时间，以a）在哈佛、马萨诸塞州总医院和广泛的研究合作网络的一流环境中开发以患者为导向的研究计划; B）扩大能力，为更多以患者为导向的研究初级研究者提供更深入的指导。 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。2型糖尿病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2型糖尿病的原因和后果。扩大对2型糖尿病前兆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 is a growing health problem. Major precursors to diabetes include obesity and genetic susceptibility. The at-risk for diabetes phenotype ("prediabetes") has been characterized by clinical research studies but needs better characterization in health care systems that serve as the major locus for prevention and treatment. This is a mid-career investigator award in patient-oriented research (K24) proposal. The candidate, James B. Meigs MD MPH, has devoted his patient-oriented research career to study of the etiology and prevention of type 2 diabetes. This award will support the following broad Specific Aims: 1. Elucidate the roles of obesity and genetic risk in the pathogenesis of type 2 diabetes by tests of hypotheses that a) adipokine dysregulation is the link whereby obesity causes type 2 diabetes; b) arrayed and specific candidate single nucleotide polymorphisms (SNPs) are associated with type 2 diabetes and related quantitative traits; 2. Translate epidemiological knowledge of the prediabetes phenotype into clinical application for population health benefit by tests of hypotheses that a) prediabetes defined by surrogate markers available in the electronic health record (EHR) has a phenotype whose metabolic profile is similar to that of prediabetes defined rigorously in clinical and epidemiologic studies; b) people with "EHR prediabetes" have health care utilization and clinical outcomes intermediate between those without EHR prediabetes and those with clinical diabetes, suggesting value in identifying such people for intervention to reduce risk; 3. Build on the candidate's successful research and mentoring program by ensuring mid-career protected time for a) patient-oriented research program development within the superb environment of Harvard, Massachusetts General Hospital and an extensive network of research collaborations; b) expanded capacity to provide a greater depth of mentoring to a larger number of patient-oriented research junior investigators. Patient-oriented research is critical to the translation of scientific knowledge into population health benefit. Type 2 diabetes is a rapidly growing clinical and public health problem. This mid-career award application seeks directly to address the need for patient-oriented research and mentoring focused on the causes and consequences of type 2 diabetes. Expanded knowledge of precursors of type 2 diabetes is critical to identify novel approaches for prevention and control of the widening diabetes epidemic.