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Krischer, J.P.* ; Liu, X.* ; Lernmark, Å.* ; Hagopian, W.A.* ; Rewers, M.J.* ; She, J.X.* ; Toppari, J.* ; Ziegler, A.-G. ; Akolkar, B.*

Predictors of the initiation of islet autoimmunity and progression to multiple autoantibodies and clinical diabetes: The TEDDY study.

Diabetes Care 45, 2271-2281 (2022)
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OBJECTIVE: To distinguish among predictors of seroconversion, progression to multiple autoantibodies and from multiple autoantibodies to type 1 diabetes in young children. RESEARCH DESIGN AND METHODS: Genetically high-risk newborns (n = 8,502) were followed for a median of 11.2 years (interquartile range 9.3-12.6); 835 (9.8%) developed islet autoantibodies and 283 (3.3%) were diagnosed with type 1 diabetes. Predictors were examined using Cox proportional hazards models. RESULTS: Predictors of seroconversion and progression differed, depending on the type of first appearing autoantibody. Male sex, Finnish residence, having a sibling with type 1 diabetes, the HLA DR4 allele, probiotic use before age 28 days, and single nucleotide polymorphism (SNP) rs689_A (INS) predicted seroconversion to IAA-first (having islet autoantibody to insulin as the first appearing autoantibody). Increased weight at 12 months and SNPs rs12708716_G (CLEC16A) and rs2292239_T (ERBB3) predicted GADA-first (autoantibody to GAD as the first appearing). For those having a father with type 1 diabetes, the SNPs rs2476601_A (PTPN22) and rs3184504_T (SH2B3) predicted both. Younger age at seroconversion predicted progression from single to multiple autoantibodies as well as progression to diabetes, except for those presenting with GADA-first. Family history of type 1 diabetes and the HLA DR4 allele predicted progression to multiple autoantibodies but not diabetes. Sex did not predict progression to multiple autoantibodies, but males progressed more slowly than females from multiple autoantibodies to diabetes. SKAP2 and MIR3681HG SNPs are newly reported to be significantly associated with progression from multiple autoantibodies to type 1 diabetes. CONCLUSIONS: Predictors of IAA-first versus GADA-first autoimmunity differ from each other and from the predictors of progression to diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Environmental Determinants; Genetic Susceptibility; Young Teddy; Risk; Appearance; Relatives; Diseases; Issues; Age
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: 45, Issue: 10, Pages: 2271-2281 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Grants NCATS NIH HHS
NIDDK NIH HHS