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

<p dir="ltr">Objective</p><p dir="ltr">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 if a child’s BMI can impact the age-related risk of first appearing IA phenotypes.</p><p dir="ltr">Research Design and Methods</p><p dir="ltr">We identified 7,724 children at risk of 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 (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 dir="ltr">Results</p><p dir="ltr">An infant’s BMI z-score was not associated with IA risk before 18 months of age (n=185, 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 (n=470, HR 1.20, 95% CI [1.04, 1.32]) and from 8.5 to 15 years (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-DR4/4,8 and not with HLA-DR3/3,4 (HLA*BMI interaction, p<0.005). </p><p dir="ltr">Conclusions</p><p dir="ltr">The contribution of BMI to risk of IA during early childhood is dependent on HLA-DR-DQ genotype more so than first appearing IA phenotype. </p><p><br></p>