Factors associated with the presence of glutamic acid decarboxylase and islet antigen-2 autoantibodies in patients with long-standing type 1 diabetes

Diabetes Metab. 2013 May;39(3):244-9. doi: 10.1016/j.diabet.2013.01.002. Epub 2013 Mar 19.


Aim: Glutamic acid decarboxylase (GAD) and/or islet antigen-2 (IA-2) autoantibodies (ab) are present in 90% of patients at the onset of type 1 diabetes (T1D). Few studies have shown that they may persist in the long-term. We analysed the frequency of GADab and IA-2ab and the factors associated with their persistency in patients with long-lasting T1D.

Methods: This cross-sectional study included 430 adult patients with T1D of at least 10-year duration, consecutively seen over one year. GADab and IA-2ab were determined by radio-binding assays. Autoantibodies to thyroperoxydase, gastric parietal cells and transglutaminase were assessed in 418 patients, and HLA DRB1 genotyping in 359. Parameters associated with the persistency of antibodies were studied by multivariate analysis.

Results: Median age at diagnosis of T1D was 12 years, and median diabetes duration was 19 years. Extrapancreatic autoimmunity was present in 38% of the patients, and associated autoimmune diseases in 21%. GADab and/or IA-2ab were found in 56% of the patients, and in 32% in those with more than 25-year diabetes duration. GADab were more frequent than IA-2ab. Female sex, an older age at diagnosis, and a shorter duration of diabetes were independently associated with the presence of ab. The same factors and the DR3 allele were associated with GADab, while only diabetes duration and the DR4 allele were associated with IA-2ab.

Conclusion: In a large proportion of the patients with T1D, the long-term persistency of diabetes-associated antibodies allows aetiological diagnosis, even far from the onset of hyperglycaemia.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / enzymology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Glutamate Decarboxylase / blood*
  • HLA-DR Antigens / genetics
  • Humans
  • Male
  • Middle Aged
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / immunology*
  • Retrospective Studies
  • Statistics, Nonparametric
  • Time Factors


  • Autoantibodies
  • HLA-DR Antigens
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase