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The Contribution of BMI to a Young Child's Risk of Islet Autoimmunity Is Dependent on HLA-DR4-DQ8 Without HLA-DR3-DQ2

Koskenniemi, Jaakko J LU ; Clasen, Joanna L ; You, Lu ; Parikh, Hemang M LU ; Vehik, Kendra LU ; Yang, Jimin ; Uusitalo, Ulla ; Veijola, Riitta LU ; Haller, Michael J and Ziegler, Anette G , et al. (2025) In Diabetes Care
Abstract

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... (More)

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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Contribution to journal
publication status
epub
subject
in
Diabetes Care
article number
dc251198
publisher
American Diabetes Association
external identifiers
  • pmid:41066490
ISSN
1935-5548
DOI
10.2337/dc25-1198
language
English
LU publication?
yes
additional info
© 2025 by the American Diabetes Association.
id
37cac762-175b-4519-89fb-448d0a7c3ed7
date added to LUP
2025-10-12 19:00:29
date last changed
2025-10-13 08:31:54
@article{37cac762-175b-4519-89fb-448d0a7c3ed7,
  abstract     = {{<p>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.</p><p>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.</p><p>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 &gt;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 &lt; 0.005).</p><p>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.</p>}},
  author       = {{Koskenniemi, Jaakko J and Clasen, Joanna L and You, Lu and Parikh, Hemang M and Vehik, Kendra and Yang, Jimin and Uusitalo, Ulla and Veijola, Riitta and Haller, Michael J and Ziegler, Anette G and Rewers, Marian J and Hagopian, William A and Akolkar, Beena and Lernmark, Åke and Toppari, Jorma and Larsson, Helena Elding and Krischer, Jeffrey P and Lynch, Kristian F}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{The Contribution of BMI to a Young Child's Risk of Islet Autoimmunity Is Dependent on HLA-DR4-DQ8 Without HLA-DR3-DQ2}},
  url          = {{http://dx.doi.org/10.2337/dc25-1198}},
  doi          = {{10.2337/dc25-1198}},
  year         = {{2025}},
}