Glutamic Acid Decarboxylase (GAD₆₅) Autoantibodies in Prediction of β-Cell Function and Remission in Recent-Onset IDDM After Cyclosporin Treatment

Abstract

We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD₆₅ Ab) were affected by cyclosporin therapy and were related to subsequent noninsulin-requiring remission and loss of glucagon-stimulated C-peptide response in 132 recent-onset insulindependent diabetes mellitus (IDDM) patients treated with cyclosporin or placebo for 12 months. GAD₆₅ Ab were detected in a quantitative radioligand assay using as tracer recombinant, in vitro translated, human islet [³⁵S]methionine-labeled GAD₆₅. GAD₆₅ Ab were found at onset in 66% (87 of 132) of IDDM patients and in 1% (1 of 100) of healthy control subjects. The prevalence of GAD₆₅ Ab and median GAD₆₅ Ab levels did not change in serum samples taken 3, 6, 9, and 12 months after study entry in either the cyclosporin- or the placebo-treated groups. The presence or absence of GAD₆₅ Ab at study entry did not predict non-insulin-requiring remission in either cyclosporin- or placebo-treated patients. However, the relative (compared with 0 months) glucagon-stimulated C-peptide response was more than 30% lower in GAD₆₅ Ab⁺ patients receiving placebo at 9 and 12 months compared with the GAD₆₅ Ab⁻ placebo patients (P < 0.035). Islet cell cytoplasmic antibody (ICA) and GAD₆₅ Ab⁺ placebotreated patients showed no significant differences in stimulated C-peptide levels compared with those who were ICA⁻ and GAD₆₅ Ab⁺, suggesting that ICA was not independently associated with loss of (β-cell function. We conclude that GAD₆₅ Ab at diagnosis may predict a more rapid loss of β-cell function, a finding of importance when selecting individuals at risk of developing IDDM or recent-onset IDDM patients for intervention therapy.