Tacrolimus reversibly reduces insulin secretion in paediatric renal transplant recipients

Background. Conflicting reports exist about the mechanism of tacrolimus-ind uced post-transplant diabetes mellitus. Methods. We analysed intravenous glucose tolerance tests (IVGTT) of 14 paed iatric renal transplant recipients on cyclosporin (CsA) microemulsion and 1 5 patients on tacrolimus (FK506). The groups were similar in age (13.2+/-4. 2 vs 13.0+/-3.7 years), body mass index, serum creatinine concentrations (9 6+/-60 vs 97+/-44 mu mol/l), time after renal transplantation, and cumulati ve steroid dose over 12 weeks prior to the test (3.4 vs 3.5 mg/m(2)/day, NS , Mann-Whitney). Parameters of glucose tolerance included glucose, insulin, C-peptide concentrations, and RbA1c. The mean concentrations of the primar y immunosuppressant were similar to treatments employed in other centres (C sA 165+/-59 ng ml and FK506 7.5+/-2.2 ng ml). Results. Baseline glucose concentrations were significantly higher on FK506 therapy compared with CsA microemulsion therapy. Baseline insulin concentr ations and C-peptide concentrations were identical in both treatment groups . FK506 trough levels correlated negatively with k values (glucose constant decay) in the FK506 group. There was a significant reduction of the insuli n first-phase concentrations, both after 1 min and after 3 min in the FK506 group compared with the CsA group (112+/-17 vs 237+/-57 mu U/ml, P = 0.034 ). In patients with repetitive IVGTTs, glucose constant decay and insulin p roduction improved after lowering FK506 whole-blood trough levels. Conclusions. We conclude that post-transplant glucose intolerance could be due to a dose-dependent, direct effect of FK506 on the pancreatic beta cell function, which can be controlled by dose reduction.