Unfolding the Mystery of Autoimmunity: The Environmental Determinants of Diabetes in the Young (TEDDY) Study

Abstract

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.

Graphical abstract

Figure 1

TEDDY study design. Ab, autoantibody; ADA, American Diabetes Association; q, every; WHO, World Health Organization; yr, years.

Figure 2

Persistent confirmed IAb incidence (with 95% CIs) per 1,000 person-years by age at IAb seroconversion (A), family history of type 1 diabetes (B), sex (C), and country (D).

Figure 3

Incidence of stage 3 type 1 diabetes (T1D), per 1,000 person-years by age at diagnosis (A), age of initial IAb seroconversion (25) (B), and family history of type 1 diabetes and relation to the proband (25) (C).

Figure 4

A: Incidence rate of GADA-only (A) as the first appearing autoantibody later developing into multiple autoantibodies (blue) in comparison with IAA-only later developing into multiple autoantibodies (gray). Red: Multiple autoantibodies at seroconversion, shown for comparison. B: Incidence rate of GADA-only (blue) and IAA-only (gray) as the first-appearing autoantibody but in individuals remaining positive for a single autoantibody. yrs, years.

Figure 5

A: Incidence (95% CI) of IA, CDA, and thyroid autoimmunity (thyroid peroxidase autoantibodies [TPOA] or thyroglobulin autoantibodies [THGA]). B: Incidence of clinically confirmed type 1 diabetes (T1D) and celiac disease (CD) (B).