A 12-year prospective study of the relationship between islet antibodies and beta-cell function at and after the diagnosis in patients with adult-onset diabetes

Diabetes. 2002 Jun;51(6):1754-62. doi: 10.2337/diabetes.51.6.1754.


To clarify the relationships between islet antibodies (islet cell antibody [ICA], GAD antibody [GADA], and IA-2 antibody [IA-2A]) versus the progression of beta-cell dysfunction, we have followed a group of diabetic patients from their diagnosis at 21-73 years of age. Patients with ICA had high levels of GADA and/or IA-2A at diagnosis and a more severe beta-cell dysfunction 5 years after diagnosis than those with only GADA in low concentrations. The aim of the current 12-year follow-up study was to examine the further progression of beta-cell dysfunction in relation to islet antibodies at and after diagnosis. Among 107 patients, complete beta-cell failure 12 years after diagnosis was restricted to those with islet antibodies at diagnosis (16 of 21 [77%] with multiple antibodies and 4 of 5 [80%] with only GADA). In contrast, among antibody-negative patients, fasting P-C-peptide levels were unchanged. Most GADA-positive patients (22 of 27 [81%]) remained GADA positive after 12 years. Associated with decreasing fasting P-C-peptide levels (0.85 nmol/l [0.84] at diagnosis vs. 0.51 nmol/l [0.21] 12 years after diagnosis, P < 0.05), ICA developed after diagnosis in 6 of 105 originally antibody negative mostly overweight patients. In conclusion, multiple islet antibodies or GADA alone at diagnosis of diabetes predict future complete beta-cell failure. After diagnosis, GADA persisted in most patients, whereas ICA development in patients who were antibody negative at diagnosis indicated decreasing beta-cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Fasting
  • Glutamate Decarboxylase / immunology
  • Humans
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / physiopathology*
  • Isoenzymes / immunology
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Time Factors


  • Autoantibodies
  • C-Peptide
  • ICA512 autoantibody
  • Isoenzymes
  • islet cell antibody
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2