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

J Med Genet. 2019 Sep;56(9):602-605. doi: 10.1136/jmedgenet-2018-105532. Epub 2018 Oct 4.

Abstract

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.

Keywords: diabetes; diagnostics tests; epidemiology; immunology (including allergy).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoantibodies / immunology
  • Autoimmunity*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Prospective Studies
  • Risk Assessment
  • Risk Factors

Substances

  • Autoantibodies