High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age

J Clin Endocrinol Metab. 2001 Jul;86(7):3032-8. doi: 10.1210/jcem.86.7.7658.

Abstract

It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • C-Peptide / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Fasting
  • Female
  • Glucagon
  • Glucose Tolerance Test
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / analysis
  • Humans
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / physiopathology*
  • Kinetics
  • Male
  • Membrane Proteins / immunology
  • Middle Aged
  • Nerve Tissue Proteins / immunology
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • C-Peptide
  • Glycated Hemoglobin A
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Glucagon
  • Ptprn protein, rat
  • Glutamate Decarboxylase