NDT Advance Access originally published online on February 13, 2007
Nephrology Dialysis Transplantation 2007 22(6):1743-1749; doi:10.1093/ndt/gfl820
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The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensitivity in man
1Section of Nephrology, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, 0027 Oslo, 2Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, 3Department of Medicine, Akershus University Hospital, Nordbyhagen, 4Department of Clinical Chemistry, Rikshospitalet University Hospital, University of Oslo, 5Morbid Obesity Center, the Hospital in Vestfold HF, 3103 Tønsberg and 6Institute of Clinical Medicine, University of Tromsø, Norway
Correspondence and offprint requests to: Jøran Hjelmesæth, Morbid Obesity Center, the Hospital in Vestfold HF, Boks 2168, 3103 Tønsberg, Norway. Email: joran{at}online.no
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Abstract |
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Background. The objectives of the present study were to investigate the possible adverse effects of ciclosporin A (CsA, Sandimmun Neoral®) 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 Statistical analyses included nine patients (7M/2F, mean age 61 ± 14 years) as two patients were withdrawn due to side effects and poor compliance.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 (Secr1.phase and Secr2.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. Secr2.phase decreased significantly (30%) following CsA treatment (P = 0.045). In contrast, no significant change was observed in the average Secr1.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 Secr2.phase, but has no significant effect on Secr1.phase, in Caucasian HD patients. The mechanism behind these findings and their possible clinical implications need further study.
Keywords: ciclosporin A; glucose clamp; insulin resistance; pancreatic ß-cell function; renal transplantation
Received for publication: 22. 9.06
Accepted in revised form: 20.12.06
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J. Hjelmesaeth, A. Asberg, A. Hartmann, and T. Jenssen Reply Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3359 - 3359. [Full Text] [PDF]
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