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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Zeitschrift Diabetes Care
Quellenangaben Band: , Heft: , Seiten: , Artikelnummer: dc251198 Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, Va.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research (IDF)
Förderungen NIH HHS
JDRF
The Finnish Cultural Foundation, the Finnish Foundation for Pediatric Research