title: The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, Aarhus University Hospital, Skejby, Denmark. doc.aygen@gmail.com
authors.forename: L A
authors.initials: LA
authors.lastname: Ozbay
authors.forename: N
authors.initials: N
authors.lastname: Møller
authors.forename: C
authors.initials: C
authors.lastname: Juhl
authors.forename: M
authors.initials: M
authors.lastname: Bjerre
authors.forename: J
authors.initials: J
authors.lastname: Carstens
authors.forename: J
authors.initials: J
authors.lastname: Rungby
authors.forename: K A
authors.initials: KA
authors.lastname: Jørgensen
mesh_terms: D015992:Body Mass Index; D019703:Calcineurin / Q000187:drug effects*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000494:pharmacology*; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D007328:Insulin; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus