The Environmental Triggers of Diabetes (TEDDY)

描述(由申请人提供)：青年糖尿病的环境决定因素(TEDDY)研究于2004年由美国和欧洲的六个临床中心发起，对424,732名新生儿进行了筛查，招募了8,669名患有1型糖尿病(T1D)的高HLA风险儿童(瑞典为2525名)。我们在这项更新应用中进行的多中心前瞻性队列研究的主要目标是识别感染源、饮食因素和其他环境暴露，这些因素可能会引发或预防胰岛自身免疫和T1D以及乳糜泻的发展，这是T1D的常见共同发病。登记的婴儿每年被跟踪四次，直到4岁，此后每年两次，直到15岁。2013年，最小的孩子将为3岁，最大的8岁。到目前为止，425名儿童(瑞典145名)发展为持续性胰岛自身抗体，117名儿童(瑞典30名)发展为T1D。此次更新申请的具体目的是：1)跟踪8,669名患有胰岛自身免疫以及糖尿病和乳糜泻的高危儿童的Teddy队列5年以上；2)根据标准Teddy方案收集所有计划的生物标本和流行病学数据，并继续保持高保留率和遵从性，并密切监测样本和数据质量；3)在适当的时间使用嵌套病例对照研究设计进行计划的实验室分析，以回答与Teddy研究目标相关的特定科学问题和假设；4)与Teddy数据协调中心合作(由一份单独的UC4合同资助)分析和发布实验室和流行病学数据；5)指导正在进行的Teddy项目，让瑞典Teddy诊所调查人员和工作人员参与研究指导委员会和小组委员会的工作。这些目标对于以下长期科学目标至关重要：A)确定触发或防止特定胰岛自身抗体(针对胰岛素、GAD65、IA-2以及抗T1D)或临床T1D发生的环境因素；B)评估影响胰岛自身免疫或T1D发生的潜在基因-环境相互作用，并深入了解机制；以及C)收集和储存用于T1D发病机制研究和开发用于T1D预测的生物标记物的标本。一个成功的研究结果应该能够更好地理解胰岛自身免疫和T1D的病因和发病机制，从而指导预防、延迟或逆转这种疾病的新策略的开发。

DESCRIPTION (provided by applicant): The Environmental Determinants of Diabetes in the Young (TEDDY) study was initiated in 2004 by six clinical centers in the United States and Europe, and screened 424,732 newborns to enroll 8,669 children (2525 in Sweden) at increased HLA risk for type 1 diabetes (T1D). The primary objective of our multi-center, prospective cohort study in this renewal application is the identification of infectious agents, dietary factors, and other environmental exposures that may trigger or protect against the development of islet autoimmunity and T1D as well as celiac disease, a common co-morbidity to T1D. Enrolled infants are followed four times per year until age 4 and twice a year thereafter until age 15. In 2013, the youngest children will be 3 and the oldest 8 years of age. So far, 425 children (145 in Sweden) have developed persistent islet autoantibodies and 117 (30 in Sweden) have developed T1D. The specific aims of this renewal application are to: 1) Follow the TEDDY cohort of 8,669 high-risk children for development of islet autoimmunity and diabetes and celiac disease for 5 more years; 2) Collect all planned biological specimens and epidemiological data according to the standard TEDDY protocol with continued high retention and compliance and close monitoring of sample and data quality; 3) Perform planned laboratory analyses at appropriate times using a nested case-control study design to answer specific scientific questions and hypotheses pertinent to the TEDDY study goals; 4) Analyze and publish laboratory and epidemiological data in collaboration with the TEDDY Data Coordinating Center (funded by a separate UC4 contract), and 5) Guide the ongoing TEDDY project by participation of Sweden TEDDY clinic investigators and staff in the work of the study Steering Committee and sub-committees. These aims are crucial to the long-term scientific goals to A) to identify environmental factors that trigger or protect against the development of defined islet autoantibodies (against insulin, GAD65, IA-2 as well as ZnT8) or clinical T1D; B) to assess potential gene-environment interactions affecting development of islet autoimmunity or T1D, and to gain insight on mechanisms; and C) to collect and bank specimens for studies of T1D pathogenesis and development of biomarkers for T1D prediction. A successful study outcome should allow better understanding of the etiology and pathogenesis of islet autoimmunity and T1D, thereby guiding development of new strategies to prevent, delay, or reverse the disease.