A2 Refereed review article in a scientific journal
Looking back at the TEDDY study: lessons and future directions
Authors: Lernmark, Ake; Agardh, Daniel; Akolkar, Beena; Gesualdo, Patricia; Hagopian, William A.; Haller, Michael J.; Hyoty, Heikki; Johnson, Suzanne Bennett; Larsson, Helena Elding; Liu, Edwin; Lynch, Kristian F.; Mckinney, Eoin F.; Mcindoe, Richard; Melin, Jessica; Norris, Jill M.; Rewers, Marian; Rich, Stephen S.; Toppari, Jorma; Triplett, Eric; Vehik, Kendra; Virtanen, Suvi M.; Ziegler, Anette-G.; Schatz, Desmond A.; Krischer, Jeffrey
Publisher: Springer Science and Business Media LLC
Publishing place: BERLIN
Publication year: 2025
Journal: Nature Reviews Endocrinology
Journal name in source: Nature Reviews Endocrinology
Journal acronym: NAT REV ENDOCRINOL
Volume: 21
Issue: 3
First page : 154
Last page: 165
Number of pages: 12
ISSN: 1759-5029
eISSN: 1759-5037
DOI: https://doi.org/10.1038/s41574-024-01045-0
Web address : https://www.nature.com/articles/s41574-024-01045-0
The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years) of 8,667 children showed high retention and compliance. End points of the presence of autoantibodies against insulin, GAD65, IA-2 and ZnT8 revealed the HLA-associated early appearance of insulin autoantibodies (1-3 years of age) and the later appearance of GAD65 autoantibodies. Competing autoantibodies against tissue transglutaminase (marking coeliac disease autoimmunity) also appeared early (2-4 years). Genetic and environmental factors, including enterovirus infection and gastroenteritis, support mechanistic differences underlying one phenotype of autoimmunity against insulin and another against GAD65. Infant growth and both probiotics and high protein intake affect the two phenotypes differently, as do serious life events during pregnancy. As the end of the TEDDY sampling phase is approaching, major omics approaches are in progress to further dissect the mechanisms that might explain the two possible endotypes of T1DM.This Review outlines the screening, enrolment and recruitment challenges in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. The key findings related to the first primary end point are discussed, and future directions of study are highlighted.
Funding information in the publication:
The TEDDY study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract no. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work is supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
