PuSH - Publication Server of Helmholtz Zentrum München

Koskenniemi, J.J.* ; Clasen, J.L.* ; You, L.* ; Parikh, H.M.* ; Vehik, K.* ; Yang, J.* ; Uusitalo, U.* ; Veijola, R.* ; Haller, M.J.* ; Ziegler, A.-G. ; Rewers, M.J.* ; Hagopian, W.A.* ; Akolkar, B.* ; Lernmark, A.* ; Toppari, J.* ; Larsson, H.E.* ; Krischer, J.P.* ; Lynch, K.F.* ; Germany clinical center (Sanverdi, C. ; Heublein, A. ; Hummel, S. ; Knopff, A. ; Köger, M. ; Koletzko, S. ; Ramminger, C. ; Roth, R. ; Schmidt, J. ; Scholz, M. ; Stock, J. ; Warncke, K. ; Müller, L. ; Winkler, C.)

The contribution of BMI to a young child's risk of islet autoimmunity is dependent on HLA-DR4-DQ8 without HLA-DR3-DQ2.

Diabetes Care:dc251198 (2025)
DOI PMC
OBJECTIVE: Childhood obesity may impact the risk of islet autoimmunity (IA). The trajectory of BMI through childhood resembles the early peak incidence of first-appearing autoantibodies against insulin (IAA-first) but not GAD65 (GADA-first). We studied whether a child's BMI can impact the age-related risk of first-appearing IA phenotypes. RESEARCH DESIGN AND METHODS: We identified 7,724 children at risk for IA with at least three BMI measurements in The Environmental Determinants of Diabetes in the Young (TEDDY) study. We modeled the risk of IAA-first, GADA-first, and IA overall on a child's BMI z score and change in BMI during infancy (age 2 weeks to 1.5 years, n = 7,724), early childhood (age 1.5-8.5 years, n = 6,396), and puberty (age 8.5-15 years, n = 4,732) using joint modeling of longitudinal BMI and time-to-event IA. RESULTS: An infant's BMI z score was not associated with IA risk before 18 months of age (n = 185, hazard ratio [HR] 1.03 [95% CI 0.88, 1.19]). In contrast, a child's BMI correlated with an increased risk of IA from 1.5 to 8.5 years of age (n = 470, HR 1.20 [95% CI 1.04, 1.32]) and from 8.5 to 15 years of age (n = 209, HR 1.27 [95% CI 1.09, 1.49]). No interactions with first-appearing IA phenotypes were observed. However, high BMI z score (SD >0.5) from age 9 months increased the risk of IA in early childhood, specifically for children with HLA-DR4/4 or HLA-DR4/8 and not with HLA-DR3/3 or HLA-DR3/4 (HLA * BMI interaction, P < 0.005). CONCLUSIONS: The contribution of BMI to risk of IA during early childhood is dependent on the HLA-DR-DQ genotype more so than the first-appearing IA phenotype.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: , Issue: , Pages: , Article Number: dc251198 Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Grants NIH HHS
JDRF
The Finnish Cultural Foundation, the Finnish Foundation for Pediatric Research