Epidemiology of Type 2 Diabetes Mellitus

我们建议在纽约西部研究的参与者中全面评估2型糖尿病的一系列炎性、抗原性和内皮生物标记物。我们将召回近3000名队列成员，并确定类型2 DM的转换者。使用病例对照方法，我们将测试以下特定目标：1)确定慢性炎症的生物标记物包括CRP、TNFpha、IL6是否预测糖尿病的发生；2)评估包括E-选择素、sICAM1和sVCAM1在内的内皮功能标记物是否预测DM；以及3)确定谷氨酸脱羧酶(GAD)和IA2的抗体是否识别表型2型糖尿病患者的一个亚型。我们假设免疫系统的慢性失调是2型糖尿病的有效预测因子。病例将是自1996-1998年基线检查以来发展为2型糖尿病的人。我们建议在研究的设计阶段对性别、种族、基线检查年份和基线血糖类别进行控制。对照将与这些变量上的病例进行3：1的匹配。关于危险因素的基线信息，包括年龄、体脂、脂蛋白、体力活动、糖尿病家族史和吸烟，将被用来评估混淆和效果修改。将提供暴露信息的基线血浆样本已在我们的生物标本库中以高水平的标准化和精确度收集、处理和冷冻，并立即进行现场离心法和冷冻法。建议的暴露是最先进的措施，将在作为几项国家研究核心实验室的实验室进行分析。鉴于2型糖尿病的流行病性质，以及它可能是可预防的，拟议的研究具有重要意义。更好地理解2型糖尿病的病因学，更好地定义“高危”表型，可以为数百万患有糖尿病的高危人群提供健康益处。

We propose to comprehensively evaluate a series of inflammatory, antigenic, and endothelial biomarkers for type 2 diabetes mellitus among participants in the Western New York Study. We will recall nearly 3000 cohort members and identify converters to type 2 DM. Using a case-control approach, we will test the following Specific Aims: 1) determine if biomarkers of chronic inflammation including CRP, TNFalpha, IL6 predict incident DM; 2) evaluate whether markers of endothelial function including E-selectin, sICAM1, and sVCAM1 predict DM; and 3) determine if antibodies to glutamic acid decarboxylase (GAD) and IA2 identify a subtype of phenotypic type 2 diabetic persons. We hypothesize that chronic dysregulation of the immune system is a potent predictor of type 2 DM. Cases will be persons who have developed type 2 DM since their baseline examination in 1996- 1998. We propose to control for sex, race, year of baseline exam, and baseline glycemic category in the design phase of the study. Controls will be matched 3:1 to the cases on these variables. Baseline information on risk factors including age, body fat, lipoproteins, physical activity, family history of DM, and smoking will be used to evaluate confounding and effect modification. Baseline plasma samples that will provide the exposure information have been collected, handled, and frozen with a high level of standardization and precision with immediate on-site centrifugation and freezing in our Biological Specimen Bank. The exposures proposed represent state-of-the-art measures and will be assayed in laboratories that serve as CORE labs for several national studies. The proposed research is of great importance due to the epidemic nature of type 2 DM, and the promise that it may be preventable. A better understanding of the etiology of type 2 and a better definition of the "at risk" phenotype can provide health benefits for the millions at risk for acquiring DM.