The Environmental Determinants of Diabetes in the Young (TEDDY), a multicenter prospective cohort study, was initiated in 2003 to identify environmental factors that trigger or protect against the development of islet autoimmunity and type 1 diabetes (T1D). A successful study outcome should allow better understanding of the etiology and pathogenesis of T1D and the development of new strategies to prevent, delay, or reverse the disease. Newborns are screened by HLA-DR.DQ genotyping to identify those at increased risk for T1D. Eligible children are followed four times per year until 4 years of age and twice a year thereafter until 15 years of age. The specific aims of this Clinical Center renewal application are to: 1. Complete this Center's contribution to the HLA-DR.DQ screening of 361,000 newborns and enrollment of 7,800 high-risk infants into intensive prospective follow-up to achieve the overall TEDDY goals. 2. Refine strategies to retain subjects enrolled in the follow-up and collect all planned biological specimens and epidemiological data according to the standard protocol including close monitoring of performance and sample/data quality. 3. Ascertain prospectively development of islet autoantibodies and clinical T1D in the study subjects. 4. Perform planned laboratory tests at appropriate times using a nested case-control study design to answer specific scientific questions and hypotheses pertinent to the TEDDY study goals. 5. Analyze and publish laboratory and epidemiological data in collaboration with the TEDDY Data Coordinating Center (funded by a separate contract). 6. Guide the ongoing TEDDY project by participation of the Clinical Center investigators and staff in work of the study Steering Committee and sub-committees.