{"doi":"10.2337/dc25-1198","title":"The Contribution of BMI to a Young Child’s Risk of Islet Autoimmunity Is Dependent on HLA-DR4-DQ8 Without HLA-DR3-DQ2","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 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.","journal":"Diabetes Care","year":2025,"id":577484,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1307233,"name":"Joanna Clasen","orcid":"0000-0003-4231-5740","position":1,"is_corresponding":false},{"id":787689,"name":"Lu You","orcid":"0000-0002-9400-2060","position":2,"is_corresponding":false},{"id":5962,"name":"Hemang Parikh","orcid":"0000-0002-9076-6709","position":3,"is_corresponding":false},{"id":95834,"name":"Kendra Vehik","orcid":"0000-0001-6243-6772","position":4,"is_corresponding":false},{"id":536208,"name":"Jimin Yang","orcid":"0000-0002-9829-6916","position":5,"is_corresponding":false},{"id":500513,"name":"Ulla Uusitalo","orcid":"0000-0001-9132-7727","position":6,"is_corresponding":false},{"id":414042,"name":"Riitta Veijola","orcid":"0000-0002-6557-270X","position":7,"is_corresponding":false},{"id":356520,"name":"Michael J. 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