PuSH - Publication Server of Helmholtz Zentrum München

Lernmark, Å.* ; Agardh, D.* ; Akolkar, B.* ; Gesualdo, P.* ; Hagopian, W.A.* ; Haller, M.J.* ; Hyöty, H.* ; Johnson, S.B.* ; Larsson, H.E.* ; Liu, E.* ; Lynch, K.F.* ; McKinney, E.F.* ; McIndoe, R.* ; Melin, J.* ; Norris, J.M.* ; Rewers, M.* ; Rich, S.S.* ; Toppari, J.* ; Triplett, E.W.* ; Vehik, K.* ; Virtanen, S.M.* ; Ziegler, A.-G. ; Schatz, D.A.* ; Krischer, J.*

Looking back at the TEDDY study: Lessons and future directions.

Nat. Rev. Endocrinol., DOI: 10.1038/s41574-024-01045-0 (2024)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Diabetes-associated Autoantibodies; Celiac-disease Autoimmunity; Hydrolyzed Infant Formula; Hl-a Antigens; Islet Autoimmunity; Environmental Determinants; Genetic Risk; Young Teddy; Respiratory-infections; Rising Incidence
ISSN (print) / ISBN 1759-5029
e-ISSN 1759-5037
Journal Nature Reviews - Endocrinology
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Grants
University of Colorado
NIH/NCATS Clinical and Translational Science Awards to the University of Florida
JDRF
Centers for Disease Control and Prevention (CDC)
National Institute of Environmental Health Sciences (NIEHS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)