GLUTAMIC-ACID DECARBOXYLASE (GAD(65)) AUTOANTIBODIES IN PREDICTION OF BETA-CELL FUNCTION AND REMISSION IN RECENT-ONSET IDDM AFTER CYCLOSPORINE TREATMENT

We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD(65) 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 insulin-dependent diabetes mellitus ((IDDM) patients treated with cyclosporin or placebo for 12 months. GAD(65) Ab were detected in a quantitative radioligand assay using as tracer recombinant, in vitro translated, human islet [S-35]methionine-labeled GAD(65). GAD(65) 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 GAD,, Ab and median GAD(65) 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 GAD(65) Ab at study entry did not predict non-insulin-requiring remission in either cyclesporin- or placebo-treated patients. However, the relative (compared with 0 months) glucagon-stimulated C-peptide response was more than 30% lower in GAD(65) Ab(+) patients receiving placebo at 9 and 12 months compared with the GAD(65) Ab(-) placebo patients (P < 0.035). Islet cell cytoplasmic antibody (ICA) and GAD(65) Ab(+) placebo-treated patients showed no significant differences in stimulated C-peptide levels compared with those who were ICA(-) and GAD(65) Ab(+), suggesting that ICA was not independently associated with loss of beta-cell function. We conclude that GAD(65) Ab at diagnosis may predict a more rapid loss of beta-cell function, a finding of importance when selecting individuals at risk of developing IDDM or recent-onset (IDDM patients for intervention therapy.