No change in insulin sensitivity in renal transplant recipients converted from standard to once-daily prolonged release tacrolimus

作者：Midtvedt Karsten^*; Jenssen Trond; Hartmann Anders; Nils Tore Vethe; Bergan Stein; Havnes Kjerstin; A**erg Anders

来源：Nephrology Dialysis Transplantation, 2011, 26(11): 3767-3772.

DOI：10.1093/ndt/gfr153

• insulin secretion and sensitivity
• once-daily tacrolimus
• renal transplantation

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 mu g/mL (P = 0.037) and Tac max from 21.3 +/- 8.4 to 15.2 +/- 3.5 mu g/L (P = 0.001). Tac AUC(0-24) was reduced from 265 +/- 112 to 218 +/- 47 mu g x 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 mu mol/min/kg/(pmol/L insulin), P = 0.99] nor any change in first (334 +/- 274 versus 353 +/- 248 mu IU x min/mL, P = 0.41) or second phase insulin secretion (224 +/- 155 versus 263 +/- 210 mu IU x 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.

• 出版日期2011-11