Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study

Research output: Contribution to journalArticle


Background: Progression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown. Methods: In 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression. Results: Islet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93). Conclusions: Genetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.


  • Andreas Beyerlein
  • Ezio Bonifacio
  • Kendra Vehik
  • Markus Hippich
  • Christiane Winkler
  • Brigitte I. Frohnert
  • Andrea K. Steck
  • William A. Hagopian
  • Jeffrey P. Krischer
  • Åke Lernmark
  • Marian J. Rewers
  • Jin Xiong She
  • Jorma Toppari
  • Beena Akolkar
  • Stephen S. Rich
  • Anette G. Ziegler
  • TEDDY Study Group
External organisations
  • Klinikum rechts der Isar
  • Dresden University of Technology
  • Helmholtz Zentrum München
  • University of South Florida
  • University of Colorado
  • Pacific Northwest Diabetes Research Institute
  • Turku University Hospital
  • University of Turku
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • University of Virginia
  • Technical University of Munich
  • Augusta University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Endocrinology and Diabetes


  • diabetes, diagnostics tests, epidemiology, immunology (including allergy)
Original languageEnglish
Pages (from-to)602-605
JournalJournal of Medical Genetics
Issue number9
Publication statusPublished - 2019
Publication categoryResearch