Association of diabetes-related autoantibodies with the incidence of asthma, eczema and allergic rhinitis in the TRIGR randomised clinical trial

Diabetologia. 2020 Sep;63(9):1796-1807. doi: 10.1007/s00125-020-05188-3. Epub 2020 Jun 17.

Abstract

Aims/hypothesis: This paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema.

Methods: A total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10 years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9-11 years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity.

Results: The cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9-11 years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together.

Conclusions/interpretation: The findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first.

Trial registration: ClinicalTrials.gov NCT00179777 Graphical abstract.

Keywords: Asthma; Autoimmunity; Eczema; Rhinitis; Type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / epidemiology*
  • Asthma / immunology
  • Autoantibodies / immunology*
  • Caseins
  • Child
  • Dermatitis, Atopic / epidemiology*
  • Dermatitis, Atopic / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Infant Formula
  • Insulin Antibodies / immunology
  • Male
  • Milk
  • Randomized Controlled Trials as Topic
  • Rhinitis, Allergic / epidemiology*
  • Rhinitis, Allergic / immunology
  • Zinc Transporter 8 / immunology

Substances

  • Autoantibodies
  • Caseins
  • ICA512 autoantibody
  • Insulin Antibodies
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • anti-GAD65 autoantibody
  • islet cell antibody
  • casein hydrolysate

Associated data

  • ClinicalTrials.gov/NCT00179777