In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune diseases has been elusive due to poor understanding of the environmental causes and their interactions with common predisposing or protective genetic variants. In 2002, the NIDDK established The Environmental Determinants of Diabetes in the Young (TEDDY) consortium to advance understanding of the causes and the natural history of type 1 diabetes and other autoimmune diseases. The overarching goal of TEDDY is to inform novel approaches to primary prevention of autoimmunity. In this large international prospective birth cohort study, standardized information has been collected concerning candidate environmental exposures along with serial blood, stool, nasal swab, and other biosamples, with creation of a central repository of data and biologic samples for hypothesis-based research. This review summarizes TEDDY’s major contributions to our understanding of environmental triggers, drivers, and modifiers of autoimmunity, and gene-environment interactions, leading to type 1 diabetes.