Combined screening for autoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM. The DENIS Study Group. Deutsche Nikotinamid Interventions-Studie

Diabetologia. 1996 Nov;39(11):1351-6. doi: 10.1007/s001250050582.


To determine the value of antibodies to the intracytoplasmic domain of the tyrosine phosphatase IA-2 (anti-IA-2ic) and glutamic acid decarboxylase (GADA) for identification of subjects at risk for insulin-dependent diabetes mellitus (IDDM) we investigated 1238 first degree relatives of patients with IDDM for the presence of anti-IA-2ic and GADA and compared the results with cytoplasmic islet cell antibodies (ICA). Anti-IA-2ic were observed in 54 (4.4%) first degree relatives, in 51 of 86 (59.3%) ICA positive relatives and in 3 of 4 individuals who developed overt IDDM within a follow-up period of 1 to 28 months. GADA were found in 78 of 1238 (6.3%) first degree relatives. They were detected in 22 of 35 (62.9%) sera with ICA alone and in 1 of 3 subjects with anti-IA-2ic in the absence of ICA. Of the 1238 subjects 37 (3.0%) sera were positive for all three antibodies. Both anti-IA-2ic and GADA were positively correlated with high levels of ICA. Anti-IA-2ic and GADA were detected in 39.1 and 47.8% of subjects with ICA of less than 20 Juvenile Diabetes Foundation units (JDF-U) but in 66.7 and 76.2% of individuals with ICA of 20 JDF-U or more, respectively (p < 0.05). The levels of ICA and GADA in first degree relatives with at least one additional marker were significantly higher than in subjects with ICA alone (p < 0.005) or GADA alone (p < 0.03). The combination of anti-IA-2ic and GADA identified 84.9% of all ICA positive subjects and 93.7% of individuals with high level ICA (> or = 20 IDF-U). All 4 individuals who progressed to IDDM had either IA-2ic or GADA. Our data indicate that primary screening for anti-IA-2ic and GADA provides a powerful approach with which to identify subjects at risk for IDDM in large-scale population studies which may represent the basis for the design of new intervention strategies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Autoantibodies / analysis*
  • Autoantibodies / immunology
  • Biomarkers
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Family
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Follow-Up Studies
  • Glutamate Decarboxylase / analysis
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Infant
  • Islets of Langerhans / immunology*
  • Male
  • Middle Aged
  • Prevalence
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / analysis
  • Protein Tyrosine Phosphatases / immunology*
  • Radioligand Assay
  • Recombinant Proteins / immunology
  • Risk Factors


  • Autoantibodies
  • Biomarkers
  • Recombinant Proteins
  • islet cell antibody
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Glutamate Decarboxylase