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. 2022 Oct 1;45(10):2271-2281.
doi: 10.2337/dc21-2612.

Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study

Jeffrey P Krischer  1 , Xiang Liu  1 , Åke Lernmark  2 , William A Hagopian  3 , Marian J Rewers  4 , Jin-Xiong She  5 , Jorma Toppari  6   7 , Anette-G Ziegler  8 , Beena Akolkar  9 ; TEDDY Study Group
Collaborators, Affiliations

Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study

Jeffrey P Krischer et al. Diabetes Care. .

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00279318.

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Figures

Figure 1
Figure 1
TEDDY study population. multiple ab+, positive for multiple autoantibodies.
See this image and copyright information in PMC

References

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