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

We have investigated whether glutamic acid decarboxylase (GAD) autoant ibodies (GAD(65) Ab) were affected by cyclosporin therapy and were rel ated to subsequent noninsulin-requiring remission and loss of glucagon -stimulated C-peptide response in 132 recent-onset insulin-dependent d iabetes 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 s ubjects. The prevalence of GAD,, Ab and median GAD(65) Ab levels did n ot change in serum samples taken 3, 6, 9, and 12 months after study en try in either the cyclosporin- or the placebo-treated groups. The pres ence or absence of GAD(65) Ab at study entry did not predict non-insul in-requiring remission in either cyclesporin- or placebo-treated patie nts. However, the relative (compared with 0 months) glucagon-stimulate d 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) an d GAD(65) Ab(+) placebo-treated patients showed no significant differe nces in stimulated C-peptide levels compared with those who were ICA(- ) and GAD(65) Ab(+), suggesting that ICA was not independently associa ted with loss of beta-cell function. We conclude that GAD(65) Ab at di agnosis may predict a more rapid loss of beta-cell function, a finding of importance when selecting individuals at risk of developing IDDM o r recent-onset (IDDM patients for intervention therapy.