The Environmental Determinants of Diabetes in the Young (TEDDY) Study, Washington Clinical Center

项目摘要/摘要 青年糖尿病的环境决定因素(Teddy)研究于2003年由6名临床医生发起 美国和欧洲的中心，包括我们的中心，以确定感染源、饮食因素或其他 可能触发或预防胰岛自身免疫和1型发展的环境暴露 糖尿病(T1D)。其他长期科学目标包括评估潜在的基因环境 影响胰岛自身免疫或T1D发展的相互作用，了解触发机制 通过详细的多组学分析，并与更广泛的科学界共享收集的样本 T1D发病机制及预防的研究。 共有424,788名新生儿接受了人类白细胞抗原-DR、DQ基因分型筛查，以确定高危儿童 对于T1D和8,676名登记参加季度随访的人，直到4岁，从那以后每半年一次，直到15岁。现在， 在登记开始13年后，5731人(66%)仍然积极参与该方案。我们的华盛顿州 临床中心招募了1376名Teddy参与者。截至18年2月28日，其中83人已发展为持续性 确诊的胰岛自身抗体和29例已被诊断为T1D。 对整个队列的生物样本进行了详细的分析，以及更全面的多项研究 对选定个体的组学分析，将提供丰富的数据集，以补充密集收集的 暴露数据和高效确定整个队列中的胰岛自身免疫和T1D终结点。 这项多中心前瞻性队列研究的续签申请在未来5年的具体目标是： 1.跟随Teddy高危儿童队列，患胰岛自身免疫、糖尿病、 乳糜泻和15岁以下的自身免疫性甲状腺疾病；收集生物 标本和流行病学数据符合研究方案。 2.确定遗传、表观遗传学、转录组、蛋白质组和代谢组学决定因素 研究参与者的胰岛自身免疫和T1D。 3.前瞻性地评估研究中的传染病、饮食和其他环境暴露 参与者，作为胰岛自身免疫的触发者和/或进展到T1D的促进者。 一个成功的研究结果将提供前所未有的深度和广度的数据集，以帮助阐明 胰岛自身免疫性T_1D和T_1D的病因和发病机制 密切相关的自身免疫性疾病。研究结果将支持制定新的预防战略， 延缓或逆转疾病。

PROJECT SUMMARY/ABSTRACT The Environmental Determinants of Diabetes in the Young (TEDDY) study was initiated in 2003 by six clinical centers in the United States and Europe, including ours, to identify infectious agents, dietary factors, or other environmental exposures that may trigger or protect against the development of islet autoimmunity and type 1 diabetes (T1D). Additional long-term scientific goals include assessment of potential gene-environment interactions affecting development of islet autoimmunity or T1D, gaining insight on triggering mechanisms through detailed multi-omics analyses, and sharing collected specimens with broader scientific community for studies of T1D pathogenesis and prevention. A total of 424,788 newborns were screened by HLA-DR,DQ genotyping to identify children at increased risk for T1D and 8,676 enrolled for quarterly follow-up until age 4 and semi-annually thereafter until age 15. Now, 13 years after enrollment began, 5731 (66%) remain actively engaged in the protocol. Our Washington State Clinical Center enrolled 1,376 TEDDY participants. As of 2/28/18, 83 of those have developed persistent confirmed islet autoantibodies and 29 have been diagnosed with T1D. Detailed analyses of biological samples from the entire cohort, along with even more comprehensive multi- omics analyses in selected individuals, will provide a rich dataset to complement the intensive collection of exposure data and highly efficient ascertainment of islet autoimmunity and T1D endpoints in the entire cohort. Specific aims of this renewal application for this multi-center, prospective cohort study for the next 5 years are: 1. Follow the TEDDY cohort of high-risk children for development of islet autoimmunity, diabetes, celiac disease and autoimmune thyroid disease until 15 years of age; collect biological specimens and epidemiological data according to the study protocol. 2. Characterize genetic, epigenetic, transcriptomic, proteomic and metabolomic determinants of islet autoimmunity and T1D in the study participants. 3. Prospectively assess infectious, dietary and other environmental exposures of study participants, as triggers of islet autoimmunity and/or promotors of progression to T1D. A successful study outcome will provide a dataset unprecedented in depth and breadth, to help elucidate specific exposures and mechanisms serving in the etiology and pathogenesis of islet autoimmunity, T1D, and closely related autoimmune diseases. The results will support the development of new strategies to prevent, delay, or reverse the disease.