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

  • 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
Publishing year: 2018-10-04
Language: English
Publication/Series: Journal of Medical Genetics
Document type: Journal article
Publisher: BMJ Publishing Group

Abstract english

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.


  • Medical Genetics
  • Endocrinology and Diabetes
  • diabetes
  • diagnostics tests
  • epidemiology
  • immunology (including allergy)


  • Diabetes and Celiac Unit
  • ISSN: 0022-2593
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79


Jan Waldenströms gata 35, Malmö


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00