Family history of type 2 diabetes delays development of type 1 diabetes in TEDDY children with islet autoimmunity
Year: 2025
Type: article
Study design: Observational Study
Abstract: AIMS/HYPOTHESIS: The aetiology of type 1 diabetes remains elusive. Family history of type 1 diabetes increases the disease risk but the role of other autoimmune diseases or type 2 diabetes in the family are unclear. Here, we aimed to analyse the effect of family history of diabetes and autoimmune diseases on development of islet autoimmunity and progression to type 1 diabetes. METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study is a prospective observational cohort study of children recruited as newborns in 2004-2010 at clinical centres in Finland, Germany, Sweden and the USA. A total of 8676 children with high-risk HLA-DR-DQ genotype for type 1 diabetes fulfilled the eligibility criteria for regular follow-up. Questionnaire-based family history of all types of diabetes and autoimmune diseases among first- and second-degree relatives (FDRs and SDRs; data available for 8558 and 7479 children, respectively) was collected. The main outcomes were development of islet autoimmunity and progression from autoimmunity to type 1 diabetes. Data until 31 January 2016 were analysed. RESULTS: Persistent islet autoantibodies were found in 669 children and type 1 diabetes in 233 children (45% and 46% female sex, respectively). The median follow-up time after seroconversion was 6.5 years (IQR 3.3-8.5). Having an FDR with type 1 diabetes increased the child's risk of islet autoimmunity (HR 2.2 [95% CI 1.8, 2.8]; p<0.001), particularly if the father or sibling had type 1 diabetes. Islet autoimmunity was also associated with family history of type 1 diabetes in an SDR when participants having an FDR with type 1 diabetes were excluded from the analysis (HR 1.4 [95% CI 1.1, 1.8]; p=0.017). Notably, progression from autoantibody positivity to type 1 diabetes was significantly delayed in children having type 2 diabetes in an SDR (HR 0.61 [95% CI 0.44, 0.86]; p=0.004). Islet autoimmunity or progression to type 1 diabetes were not associated with other types of diabetes or autoimmune diseases in the family. CONCLUSIONS/INTERPRETATION: Family history of diabetes is differentially associated with development of islet autoimmunity and progression to type 1 diabetes. The contribution made by familial, genetic and environmental factors to the two phases of the disease pathogenesis deserves distinct analyses. DATA AVAILABILITY: Data reported here can be obtained by request at the NIDDK Central Repository website, Resources for Research (R4R), https://repository.niddk.nih.gov/ .
Source: Diabetologia
Authors: Riitta Veijola, Roy N. Tamura, Joanna L. Clasen, Helena Elding Larsson, Katharina Warncke, Andrea K. Steck, Michael J. Haller, Berglind Jonsdottir, Beena Akolkar, William A. Hagopian, Marian J. Rewers, Jin-Xiong She, Anette-Gabriele Ziegler, Jeffrey P. Krischer, Jorma Toppari, TEDDY Study Group
Institutions: Oulu University Hospital, University of Oulu, University of South Florida, Lund University, Skåne University Hospital, TUM Klinikum, Helmholtz Munich, Institute of Diabetes Research, Technical University of Munich, University of Colorado Anschutz, University of Colorado Denver, University of Florida Health, University of Florida, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Pacific Northwest Research Institute, Augusta University, University of Turku, Turku University Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
Funders: Juvenile Diabetes Research Foundation International, Oulun Yliopisto, National Institutes of Health, Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, Division of Diabetes, Endocrinology, and Metabolic Diseases
Awards: G2368025445, The Environmental Triggers of Diabetes (TEDDY) in Sweden, G3628321623, G3737848772, The TEDDY Study: Georgia/Florida Clinical Center, UF Clinical and Translational Science Award, THE TEDDY STUDY - COLORADO CLINICAL CENTER, The Environmental Determinants of Diabetes in the Young (TEDDY) Study, Washington Clinical Center, Colorado Clinical and Transational Sciences Institute, G8444128804
OpenAlex ID: W4417101049