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/ . Graphical Abstract
Veijola et al. (Mon,) studied this question.