title: No change in insulin sensitivity in renal transplant recipients converted from standard to once-daily prolonged release tacrolimus.
abstract: BACKGROUND
  New-onset diabetes after transplantation may be associated with the use of tacrolimus (Tac) causing impaired insulin release or reduced insulin sensitivity. Such effects have not been studied in renal transplant recipients receiving traditional twice-daily tacrolimus (TacBID) and then compared to the new once-daily prolonged release formulation of tacrolimus (TacOD).
  
  
  METHODS
  We performed a prospective crossover study of 20 stable non-diabetic renal transplant recipients. All patients underwent one hyperglycaemic clamp on TacBID (3.8 ± 2.2 mg/day) and a new clamp 4-6 weeks after a 1:1 mg/day switch to TacOD (4.0 ± 2.8 mg/day).
  
  
  RESULTS
  Tac trough concentrations decreased from 6.6 ± 2.9 to 5.4 ± 1.4 μg/mL (P = 0.037) and Tac max from 21.3 ± 8.4 to 15.2 ± 3.5 μg/L (P = 0.001). Tac AUC(0-24) was reduced from 265 ± 112 to 218 ± 47 μg × h/L (P = 0.12). The hyperglycaemic clamp did not detect any change in insulin sensitivity index after conversion [0.26 ± 0.21 versus 0.26 ± 0.25 μmol/min/kg/(pmol/L insulin), P = 0.99] nor any change in first (334 ± 274 versus 353 ± 248 μIU × min/mL, P = 0.41) or second phase insulin secretion (224 ± 155 versus 263 ± 210 μIU × min/mL/mmol glucose, P = 0.60) on TacBID versus TacOD.
  
  
  CONCLUSIONS
  Conversion from standard TacBID to TacOD on a 1:1 mg basis is safe. In spite of a reduced Tac exposure, there was no change in insulin release or sensitivity in renal transplant recipients.
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany. karsten.midtvedt@rikshospitalet.no
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
authors.forename: Trond
authors.initials: T
authors.lastname: Jenssen
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Nils Tore
authors.initials: NT
authors.lastname: Vethe
authors.forename: Stein
authors.initials: S
authors.lastname: Bergan
authors.forename: Kjerstin
authors.initials: K
authors.lastname: Havnes
authors.forename: Anders
authors.initials: A
authors.lastname: Åsberg
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006943:Hyperglycemia; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000628:therapy*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D016559:Tacrolimus