The long-term persistence of islet cell antibodies in Type I diabetic patients is unrelated to residual β-cell function

Islet cell antibodies (ICA) disappear in most Type I diabetic subjects within months or a few years after diagnosis, possibly reflecting the disappearance of β-cell autoantigen. In a minority of patients, ICA tend to persist indefinitely. The aim of this study was to evaluate whether the persistence of ICA reflects the persistence of functioning β-cell as a source of autoantigen immunization. In 19 longstanding Type I diabetic patients, selected for having (n = 9) detectable ICA (64.4 ± 8.01 JDF units) or not (n = 10) and matched for the duration of the disease (17.1 ± 3.6 vs 19.1 ± 1.5 yr, respectively), C-peptide secretion was evaluated by an i.v. glucagon test. The insulin requirement and metabolic control of patients with ICA were similar to those without detectable ICA. In contrast, patients with ICA were mostly females (p <0.02), older at diagnosis (p <0.02), with a higher prevalence of associated thyroid (p <0.005) and gastric (p <0.05) autoantibodies and autoimmune diseases (p <0.02). No differences were observed between patients with or without ICA in basal (0.2 ± 0.06 vs 0.10 ± 0.58 pg/ml at 0 min, NS) and glucagon-stimulated (0.23 ± 0.07 vs 0.31 ± 0.16 pg/ml at 6 min, NS) C-peptide levels, showing a virtually absent β-cell secretion in the two groups. These findings indicate that: 1) ICA in some Type I diabetic subjects may persist in the absence of a residual C-peptide secretion and therefore independently of the fate of β-cell autoantigen(s); 2) the long-term persistence of ICA identifies Type I diabetic patients as preferentially female, with an older age of onset and with other associated organ-specific autoimmunities; 3) the mechanisms of islet autoimmune response are heterogeneous.