The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensitivity in man

Background. The objectives of the present study were to investigate the possible adverse effects of ciclosporin A (CsA, Sandimmun Neoral (R)) on insulin secretion and insulin sensitivity (IS) in man. Methods. A total of 11 Caucasian non-diabetic haemodialysis (HD) patients were recruited from the Norwegian transplant waiting list to participate in this study. The patients underwent two consecutive 3 h hyperglycaemic glucose clamp procedures, before and following 2 weeks of oral CsA treatment. Statistical analyses included nine patients (7M/2F, mean age 61 +/- 14 years) as two patients were withdrawn due to side effects and poor compliance. First and second phase insulin secretion (Secr(1.phase) and Secr(2.phase)) were estimated as area under the insulin serum concentration vs time curve (AUC) during the first 10 min and the last hour of the clamp, respectively. The IS index (ISI) was calculated as the glucose disposal rate corrected for insulin levels during the last 60 min of the procedure. Results. Secr(2.phase) decreased significantly (30%) following CsA treatment (P=0.045). In contrast, no significant change was observed in the average Secr(1.phase) or ISI, although relatively large inter-individual differences were present. Calculation based on C-peptide concentrations gave the same results. No significant changes in body weight, dialysis status, patient medication or safety parameters were observed. Conclusions. Short-term treatment with CsA at doses used following transplantation seems to impair Secr(2.phase), but has no significant effect on Secr(1.phase) in Caucasian HD patients. The mechanism behind these findings and their possible clinical implications need further study.