The Environmental Triggers of Diabetes (TEDDY) in Sweden

项目总结/摘要 年轻人糖尿病的环境决定因素（TEDDY）研究始于2003年，由六个临床 在美国和欧洲的中心，包括我们的，以确定传染性病原体，饮食因素，或其他 环境暴露可能引发或防止胰岛自身免疫和1型 糖尿病（T1 D）。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T1 D发展的相互作用，深入了解触发机制 通过详细的多组学分析，并与更广泛的科学界分享收集的标本， T1 D发病机制和预防的研究。 共对424,788名新生儿进行了HLA-DR、DQ基因分型筛查，以确定高危儿童 8，676人参加了季度随访，直到4岁，此后每半年随访一次，直到15岁。现在我想， 入组13年后，5731例（66%）仍积极参与该方案。我们的泰迪瑞典 中心招募了2525名TEDDY参与者。截至2018年2月28日，有139名SWE儿童有两个或更多的胰岛 自身抗体，122人有一种胰岛自身抗体，87人被诊断患有糖尿病。 对整个队列的生物样本进行详细分析，沿着更全面的多方面分析， 在选定的个人组学分析，将提供一个丰富的数据集，以补充密集收集的 暴露数据和整个队列中胰岛自身免疫和T1 D终点的高效确定。 本多中心、前瞻性队列研究未来5年的更新申请的具体目的是： 1.跟踪TEDDY高危儿童队列中胰岛自身免疫、糖尿病、 乳糜泻和自身免疫性甲状腺疾病，直到15岁;收集生物 根据研究方案收集样本和流行病学数据。 2.表征遗传、表观遗传、转录组、蛋白质组和代谢组学决定因素， 胰岛自身免疫和T1 D的研究参与者。 3.预防性评估研究的感染、饮食和其他环境暴露 参与者作为胰岛自身免疫的触发剂、进展为T1 D的促进剂或两者。 一个成功的研究结果将提供一个前所未有的深度和广度的数据集，以帮助阐明 在胰岛自身免疫、T1 D的病因和发病机制中起作用的特定暴露和机制， 与自身免疫性疾病密切相关。研究结果将有助于制定新的预防战略， 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 TEDDY SWEDEN Center enrolled 2525 TEDDY participants. As of 2/28/18, there are 139 SWE children with two or more islet autoantibodies, 122 with one islet autoantibody and 87 who have been diagnosed with diabetes. 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, promotors of progression to T1D, or both. 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.