Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8

J Diabetes Investig. 2021 Apr;12(4):510-515. doi: 10.1111/jdi.13370. Epub 2020 Aug 26.

Abstract

Aims/introduction: This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes.

Methods: Using bridging-type enzyme-linked immunosorbent assay, IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8-86 years; median diabetes duration 7 years, range 0-58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran-Armitage trend test and multivariate logistic regression analysis.

Results: The prevalence of IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P < 0.005). Both IA-2A and ZnT8A were more frequently observed in younger patients, whereas glutamic acid decarboxylase autoantibodies was more common in older patients. Multivariate logistic regression analysis showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all anti-islet autoantibodies (P < 0.05). However, for patients diagnosed in the middle tertile (aged 11-30 years), the interaction was significant only for ZnT8A, and for those with late-onset diabetes (aged ≥31 years) only for IA-2A.

Conclusions: The current study showed that the rate of disappearance of anti-islet autoantibodies is faster in patients aged ≤10 years, and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA-2 and ZnT8 differs according to the age of onset.

Keywords: Age; Autoantibodies; Type 1 diabetes.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoantibodies / blood
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Infant
  • Middle Aged
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / immunology*
  • Young Adult
  • Zinc Transporter 8 / immunology*

Substances

  • Autoantibodies
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • PTPRN protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase