INFLAMMATORY PRECURSORS OF TYPE 2 DIABETES

描述：（改编自研究者摘要）不断增长的人口 美国和世界各地的肥胖负担一直伴随着 2型糖尿病的主要国际流行病。迫切需要进行研究， 更好地了解肥胖和两个主要机制之间的联系， 2型糖尿病的发展，即，胰岛素抵抗和受损胰岛素 分泌物最近的初步研究发现， 炎症的全身标志物和2型糖尿病之间的关系，这表明， 炎症介质参与了这种疾病的发病机制， 部分解释了肥胖引起的代谢后果。的 细胞因子肿瘤坏死因子-α（TNF-α）和瘦素可能起关键作用， 在这些过程中的作用。 研究的总体目标是确定 TNF-α、瘦素和炎症过程中的其他选定元素， 2型糖尿病的发展为了进一步阐明 促炎细胞因子与肥胖和糖尿病的关系，该研究将评估 外部和内部因素的作用假设修改或 导致炎症状态（动脉粥样硬化、慢性感染， C.肺炎和巨细胞病毒，以及社会人口统计学影响） 作为假设介导这些关联的因素（游离脂肪酸， 皮质醇、急性期反应物和内皮功能障碍）。这项研究将 使用现有的检查数据和储存的生物样本进行， 一个由15,792名中年人组成的特征明确的、基于人口的队列， 来自美国四个社区的非洲裔美国人和白色成年人（ 社区动脉粥样硬化风险研究，或ARIC），其中超过1100新 在三至九年的随访中发现了糖尿病病例。 更具体地说，将使用嵌套病例队列设计来选择一个简单的 随机抽取600例新发糖尿病病例， 从引发这些病例的研究基地中抽取了700名个人的样本。新 将排除存在抗GAD 65抗体的糖尿病病例， 这一样本，后来分别检查，以确定风险因素的特点， 成人隐匿性自身免疫性糖尿病（LADA）。在所有 研究表明，炎症前体和其他分析物的循环水平将 使用从这些人收集的冷冻血浆或血清标本进行测量 基线ARIC检查和后续随访时的参与者 考试这些炎症因子预测事件的能力 糖尿病将在事件发生时间分析中进行评价， 适应病例队列方法的风险模型。 研究人员指出，这项研究将有助于一个新兴的新焦点， 2型糖尿病的发病机制研究：慢性 炎症和先天免疫系统。他们进一步指出， 前瞻性的，以人口为基础的性质将支持的普遍性， 调查结果及其在公共卫生中的应用， 非洲裔美国人将为这一未充分研究的问题提供重要的新信息 少数民族人口。

DESCRIPTION: (Adapted from the Investigator's Abstract) The growing population burden of obesity in the U.S. and around the world has been accompanied by a major international epidemic of type 2 diabetes. Research is urgently needed to better understand the links between obesity and the two major mechanisms in the development of type 2 diabetes, i.e., insulin resistance and impaired insulin secretion. Recent preliminary studies have found some strong associations between systemic markers of inflammation and type 2 diabetes, suggesting that inflammatory mediators are involved in the pathogenesis of this disease and may partially account for the metabolic consequences ascribed to obesity. The cytokines tumor necrosis factor-alpha (TNF-alpha) and leptin may play critical roles in these processes. The overall objective of the study is to identify the contribution of TNF-alpha, leptin, and other selected elements of the inflammatory process to the development of type 2 diabetes. To further elucidate pathways that may link pro-inflammatory cytokines with obesity and diabetes, the study will evaluate the role of extrinsic and intrinsic factors hypothesized to modify or contribute to the inflammatory state (atherosclerosis, chronic infections with C. pneumoniae and cytomegalovirus, and sociodemographic influences) as well as factors hypothesized to mediate these associations (free fatty acids, cortisol, acute phase reactants, and endothelial dysfunction). The study will be conducted using existing examination data and stored biologic specimens from a well-characterized, population-based cohort of 15,792 middle-aged African-American and white adults from four U.S. communities (the Atherosclerosis Risk in Communities Study, or ARIC), in which over 1100 new cases of diabetes have been detected over three to nine years of follow-up. More specifically, a nested case-cohort design will be used to select a simple random sample of 600 incident diabetes cases and a cohort stratified random sample of 700 individuals from the study base that gave rise to the cases. New cases of diabetes who present with anti-GAD65 antibodies will be excluded from this sample and later examined separately to characterize risk factors for the development of so-called latent autoimmune diabetes in adults (LADA). In all studies, circulating levels of inflammatory precursors and other analytes will be measured using frozen plasma or serum specimens collected from these participants at the baseline ARIC examination and subsequent follow-up examinations. The ability of these inflammatory elements to predict incident diabetes will be evaluated in time-to-event analyses utilizing proportional hazards models adapted to the case-cohort approach. The investigators state that the study will contribute to an emerging new focus of research in the pathogenesis of type 2 diabetes: the role of chronic inflammation and the innate immune system. They further state that its prospective, population-based nature will support the generalizability of the findings and their application to public health, and that the large sample of African-Americans will provide important new information for this understudied minority population.