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。糖尿病的主要先兆包括肥胖和遗传易感性。糖尿病高危表型(“前驱糖尿病”)的特征是临床研究，但在作为主要预防和治疗场所的卫生保健系统中需要更好的特征。这是一项以患者为中心的研究(K24)提案的职业生涯中期研究人员奖。候选人詹姆斯·B·梅格斯医学硕士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、特定的候选单核苷酸多态(SNPs)与2型糖尿病及其相关数量性状相关； 2.通过以下假设的检验，将糖尿病前期表型的流行病学知识转化为对人群健康有益的临床应用：a)由电子健康记录(EHR)中提供的替代标记物定义的前驱糖尿病具有其代谢特征与临床和流行病学研究中严格定义的前驱糖尿病相似的表型；b)“EHR前驱糖尿病”患者的医疗保健利用和临床结果介于非EHR前驱糖尿病患者和临床糖尿病患者之间，这表明识别这类人进行干预以降低风险的价值； 3.建立在候选人成功的研究和指导计划的基础上，确保a)在哈佛、马萨诸塞州总医院的一流环境和广泛的研究合作网络中以患者为导向的研究计划开发；b)扩大能力，为更多以患者为导向的研究初级研究员提供更深入的指导。 以患者为中心的研究对于将科学知识转化为人群健康利益至关重要。2型糖尿病是一个迅速增长的临床和公共卫生问题。这项职业生涯中期奖励申请直接寻求解决以患者为导向的研究和指导的需求，重点关注2型糖尿病的原因和后果。扩大对2型糖尿病先兆的了解对于确定预防和控制不断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.