Diabetes Evaluation in Washington (DEW-IT) Clinical Cen*

1型(自身免疫性)糖尿病的病因涉及遗传和环境两方面的影响 大致相等的震级。汇集许多患者样本的大型合作安排帮助 几种致病基因多态的鉴定。环境因素的识别有 更困难的是，但也应该受益于合作的方法。糖尿病在中国的评估 华盛顿(Dew-IT)研究是一项以3.2万名受试者为基础的人群筛查计划，将确定 6,000多名患有未来糖尿病遗传风险的幼儿。将主题组与 在美国和其他地方进行的类似规模的基于人群的筛查研究应该可以 获得足够的样本量和统计能力，以确定常见的环境触发因素。 我们建议跟踪高遗传风险的受试者(Dew-IT家族和Dew-IT普通队列) 三个推测的疾病阶段：a)GAD，ICA512/IA2之一的血清转为单一抗体阳性， 和胰岛素，b)从一种确定的自身抗体进展到多种确定的自身抗体，以及c)低β细胞的发展 功能(空腹C肽)或临床糖尿病。一级亲属将按顺序 所有阶段，除b)和c)阶段外，抗体阳性的遗传风险儿童将来自 一般露水-IT队列，在密集的环境采样之前。频繁的患者抽样将包括 血清、外周血单核细胞、咽拭子、头发、尿液和粪便。我们还将调查儿童的食物摄入量、疫苗接种、 过敏、疾病和其他压力源。环境抽样还将包括选定的食品。 在病人日记中被确认。基因分型将包括HLADR-DQ和其他10个已知的糖尿病风险基因座，如 以及其他10个设计用来检测β细胞基因多态性的基因座，这些基因座可以减少有毒物质的暴露。 包括父母双方在内的三人将被收集用于TDT分析。测量的环境暴露 包括肠道病毒、膳食真菌毒素、疾控中心选择的环境毒素和暴露 由其他网站提出。疾病进展将根据基因效应、环境因素进行分析 效果，以及消失的x环境效果。疾病分期、样本收集和分析以及统计 该方法将遵循该联盟制定的协商一致的方法。总体目标是确定 启动和/或传播儿童自身免疫性糖尿病发病机制的环境因素。

The etiology of Type 1 (autoimmune) diabetes involves both genetic and environmental influences of roughly equal magnitude. Large cooperative arrangements pooling many patient samples have aided in identification of severa of the causative genetic polymorphisms. Identification of environmental factors has been more difficult, but should also benefit from a cooperative approach. The Diabetes Evaluation in Washington (DEW-IT) study is a 32,000 subject population-based screening program which will identify more than 6,000 young children at elevated genetic risk of future diabetes. Combining subject groups with similarly-sized population-based screening studies in the US and elsewhere should make it possible to achieve sufficient sample sizes and statistical power to identify common environmental triggers. We propose to follow subjects at high genetic risk (DEW-IT family and DEW-IT general cohorts) through three putative disease stages: a) seroconversion to single antibody positivity to one of GAD, ICA512/IA2, and insulin, b) progression from one to multiple defined autoantibodies, and c) development of low beta cell function (fasting C-peptide) or clinical diabetes. First degree relatives will be followed sequentially through all stages, but stages b) and c) will be augmented by antibody-positive genetically-at-risk children from the general DEW-IT cohort, prior to intense environmental sampling. Frequent patient sampling will include serum, PBMC, throat swabs, hair, urine and stool. We will also survey children on food intake, vaccinations, allergies, illnesses and other stressors. Environmental sampling will also include selected foodstuffs identified in patient diaries. Genotyping will include HLA DR-DQ and 10 other known diabetes risk loci, as well as 10 other loci designed to detect polymorphisms at beta cell genes known to mitigate toxic exposures. Trios, including both parents, will be collected for TDT analyses. Measured environmental exposures include enteroviruses, dietary mycotoxins, environmental toxins selected by the CDC, and exposures proposed by other sites. Disease progression will be analyzed with respect to gene effects, environmental effects, and gone x environment effects. Disease staging, sample collection and analyses, and statistical approach will follow the consensus approach developed by the consortium. The overall goal is to identify environmental factors intiating and/or propagating the pathogenesis of childhood autoimmune diabetes.