Family history of type 2 diabetes delays development of type 1 diabetes in TEDDY children with islet autoimmunity - UTU Research Portal

A1 Refereed original research article in a scientific journal

Family history of type 2 diabetes delays development of type 1 diabetes in TEDDY children with islet autoimmunity

Authors: Veijola, Riitta; Tamura, Roy N.; Clasen, Joanna L.; Elding Larsson, Helena; Warncke, Katharina; Steck, Andrea K.; Haller, Michael J.; Jonsdottir, Berglind; Akolkar, Beena; Hagopian, William A.; Rewers, Marian J.; She, Jin-Xiong; Ziegler, Anette-Gabriele; Krischer, Jeffrey P.; Toppari, Jorma; TEDDY Study Group

Publisher: Springer Nature

Publication year: 2025

Journal: Diabetologia

ISSN: 0012-186X

eISSN: 1432-0428

DOI: https://doi.org/10.1007/s00125-025-06613-1

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Partially Open Access publication channel

Web address : https://doi.org/10.1007/s00125-025-06613-1

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/505887258

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.

Downloadable publication

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s00125-025-06613-1.pdf

Funding information in the publication:
Open Access funding provided by University of Oulu (including Oulu University Hospital). The TEDDY study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166 and contract no. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC) and Breakthrough T1D (formerly known as JDRF). This work is supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535). The sponsors were represented in The Environmental Determinants of Diabetes in the Young (TEDDY) steering committee. The sponsors had a role in the design and conduct of the study; collection, management, analysis and interpretation of the data, and in review and approval to submit the manuscript for publication. The sponsors did not have the right to veto submission to any particular journal but did participate in the writing group’s discussion when selecting an appropriate journal for submission. The corresponding author had the final say in submitting the manuscript for publication.