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Adverse effects of cyclosporine on glucose metabolism have been reported in patients with kidney transplantation, but steroids were present in all the immunosuppressive schedules evaluated. We have studied endocrine pancreatic function (OGTT measuring plasma insulin [IRI] and c-peptide [CP]) in 3 groups of patients, matched for age and body-mass index, 16-66 months after functioning Ktx. Seven patients were treated with CsA monotherapy (group I), 7 patients with CsA plus prednisone (group II), and 6 patients with azathioprine plus prednisone (group III). Seven healthy subjects formed the control group. OGTT was normal in all patients, except one in group II (impaired glucose tolerance). There were no significant differences between the 4 groups concerning fasting blood glucose and area under the glucose curve, as well as basal insulin levels, peak insulin response to glucose, and area under the insulin curve. Basal CP, peak CP response to glucose, and area under CP curve were lower in CG than in the 3 groups of patients. Basal CP in group II (4.4 +/- 2.2 ng/ml) was higher than in group I (2.8 +/- 0.6 ng/ml, P less than 0.05). Glucose/IRI molar ratio in group II (5.7 +/- 1.4, P greater than 0.05) was lower than in group I (7.3 +/- 1.8) and CG (8.0 +/- 2.1, P less than 0.025). Our results suggest that CsA at normal dosage has no clinically important effect on beta-cell function. The indirect evidence of insulin resistance observed in patients treated with CsA plus prednisone is ascribable to corticosteroid treatment.