Inflammatory Precursors of Type 2 Diabetes

描述（由申请人提供）：本修订后的竞争性延续研究的总体目标是在3 - 9年的随访过程中，在以人群为基础的中年非裔美国人和白色男性和女性队列中，促进我们对炎症反应在2型糖尿病发展中的作用的理解。我们建议继续调查来自NHLBI支持的社区动脉粥样硬化风险（ARIC）研究的病例队列样本，收集10，275人的经验，其中1155例糖尿病病例已被检测到。我们将建立在最初资助期开发的设计基础上，在该设计中，我们以非常具有成本效益的方式选择了581例新发糖尿病病例的分层随机样本和693例个体的队列分层随机样本。 使用基线时采集和储存的血浆（糖尿病前期）检查，我们将调查潜在来源（晚期糖基化终产物蛋白，氧化应激）和炎症调节剂（吸烟）;炎症反应的其他成分（巨噬细胞抑制因子、巨噬细胞趋化蛋白-1和二肽基肽酶-IV）;和可能被炎症反应改变的碳水化合物代谢的调节剂（胰腺β-细胞功能、肠促胰岛素、生长因子、生长素释放肽、内皮细胞功能）。 这项研究将允许定义的意义，在临床和人群水平上，这一新兴的炎症和2型糖尿病发病机制的研究重点的具体方面。在最初的授权期间，收集了丰富的分析物数据库，包括细胞因子，急性期反应物，肝功能检查和脂联素，大量的事件病例，以及非洲裔美国人受试者的重要代表性，使其成为一个独特而强大的研究人群，以评估新的和新兴的假设。

DESCRIPTION (provided by applicant): The overall objective of this revised competing continuation is to advance our understanding of the role of the inflammatory response in the development of type 2 diabetes over the course of 3 to 9 years of follow-up in a population-based cohort of middle-aged African-American and white men and women. We propose to continue investigation of a case-cohort sample from the NHLBI-supported Atherosclerosis Risk in Communities (ARIC) Study, capturing the experience of 10,275 individuals, among whom 1155 incident cases of diabetes have been detected. We will build on the design developed in the initial grant period, in which we have selected, in a very cost-efficient manner, a stratified random sample of 581 incident diabetes cases and a cohort stratified random sample of 693 individuals. Using plasma collected and stored at the baseline (pre-diabetic) exam, we will investigate potential sources (advanced glycation end product proteins, oxidative stress) and modulators (smoking) of inflammation; additional components of the inflammatory response (macrophage inhibitory factor, macrophage chemo attractant protein-1 and dipeptidyl peptidase-IV); and modulators of carbohydrate metabolism potentially altered by the inflammatory response (pancreatic beta-cell function, incretins, growth factors, ghrelin, endothelial cell function). This study will allow definition of the significance, at a clinical and population level, of specific aspects of this emerging focus of research on inflammation and the pathogenesis of type 2 diabetes. The availability of a rich database of analytes assembled during the initial grant period, including cytokines, acute phase reactants, liver function tests and adiponectin, the large number of incident cases, and the significant representation of African-American subjects makes this a unique and powerful study population to evaluate new and emerging hypotheses.