The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients

• Published in: Diabetic medicine Vol. 29; no. 12; pp. e440 - e444
• Main Authors: Øzbay, L. A., Møller, N., Juhl, C., Bjerre, M., Carstens, J., Rungby, J., Jørgensen, K. A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2012; Wiley Subscription Services, Inc
• Subjects: Body Mass Index; Calcineurin - drug effects; Cross-Over Studies; Cyclosporine - pharmacology; Denmark - epidemiology; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - prevention & control; Female; Follow-Up Studies; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin - metabolism; Insulin Secretion; Kidney Transplantation - adverse effects; Male; Middle Aged; Postoperative Complications - drug therapy; Postoperative Complications - epidemiology; Postoperative Complications - metabolism; Tacrolimus - pharmacology; Denmark
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.12028

Aims The calcineurin inhibitors cyclosporine and tacrolimus are implicated in post‐transplant complications such as new‐onset diabetes after transplantation. The relative contribution of each calcineurin inhibitor to new‐onset diabetes after transplantation remains unclear. We sought to compare the impact of cyclosporine and tacrolimus on glucose metabolism in humans. Methods Eight haemodialysis patients received 8–10 days of oral treatment followed by 5‐h infusions with cyclosporine, tacrolimus and saline in a randomized, investigator‐blind, crossover study. Glucose metabolism and β‐cell function was investigated through: a hyperinsulinaemic–euglycaemic clamp, an intravenous glucose tolerance test and insulin concentration time series. Results Cyclosporine and tacrolimus decreased insulin sensitivity by 22% (P = 0.02) and 13% (P = 0.048), respectively. The acute insulin response and pulsatile insulin secretion were not significantly affected by the drugs. Conclusion In conclusion, 8–10 days of treatment with cyclosporine and tacrolimus impairs insulin sensitivity to a similar degree in haemodialysis patients, while acute insulin responses and pulsatile insulin secretion remain unaffected.