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Åke Lernmark

Principal investigator

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

Author

  • 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

Summary, in 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.

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2019

Language

English

Pages

602-605

Publication/Series

Journal of Medical Genetics

Volume

56

Issue

9

Document type

Journal article

Publisher

BMJ Publishing Group

Topic

  • Medical Genetics
  • Endocrinology and Diabetes

Keywords

  • diabetes
  • diagnostics tests
  • epidemiology
  • immunology (including allergy)

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 0022-2593