Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level

Diabet Med. 2014 Apr;31(4):466-71. doi: 10.1111/dme.12314. Epub 2013 Oct 16.

Abstract

Aims: Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control.

Methods: Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2) were measured in a cohort of 28 Czech patients with maturity-onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies.

Results: One quarter of patients with maturity-onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody-negative, but had worse glycaemic control (increased HbA1c ). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity-onset diabetes of the young and Type 1 diabetes.

Conclusions: The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity-onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of β-cell destruction induced by causes other than autoimmune ones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoantibodies / immunology*
  • Child
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucokinase / genetics
  • Glutamate Decarboxylase / immunology*
  • Glycated Hemoglobin / metabolism*
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 4 / genetics
  • Humans
  • Islets of Langerhans / immunology*
  • Male
  • Middle Aged
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / immunology*
  • Young Adult

Substances

  • Autoantibodies
  • Glycated Hemoglobin A
  • HNF1A protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • hemoglobin A1c protein, human
  • Glucokinase
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase

Supplementary concepts

  • Mason-Type Diabetes