A1 Refereed original research article in a scientific journal
The Contribution of BMI to a Young Child’s Risk of Islet Autoimmunity Is Dependent on HLA-DR4-DQ8 Without HLA-DR3-DQ2
Authors: Koskenniemi, Jaakko J.; Clasen, Joanna L.; You, Lu; Parikh, Hemang M.; Vehik, Kendra; Yang, Jimin; Uusitalo, Ulla; Veijola, Riitta; Haller, Michael J.; Ziegler, Anette G.; Rewers, Marian J.; Hagopian, William A.; Akolkar, Beena; Lernmark, Åke; Toppari, Jorma; Elding Larsson, Helena; Krischer, Jeffrey P.; Lynch, Kristian F.; TEDDY Study Group
Publisher: American Diabetes Association
Publication year: 2025
Journal:Diabetes Care
Article number: dc251198
ISSN: 0149-5992
eISSN: 1935-5548
DOI: https://doi.org/10.2337/dc25-1198
Web address : https://doi.org/10.2337/dc25-1198
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.
Funding information in the publication:
The TEDDY Study is funded by grants 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, and U01 DK128847 and contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, Centers for Disease Control and Prevention, and Breakthrough T1D (formerly JDRF). This work is supported by the Finnish Cultural Foundation, Finnish Foundation for Pediatric Research, and Kyllikki and Uolevi Lehikoinen Foundation and in part by National Institutes of Health/National Center for Advancing Translational Sciences clinical and translational science awards to the University of Florida (UL1 TR000064) and University of Colorado (UL1 TR002535)
