Background: Conflicting reports exist about the mechanism of tacrolimus-induced post-transplant diabetes mellitus.
Methods: We analysed intravenous glucose tolerance tests (IVGTT) of 14 paediatric renal transplant recipients on cyclosporin (CsA) microemulsion and 15 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 (96+/-60 vs 97+/-44 micromol/l), time after renal transplantation, and cumulative 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 HbA1c. The mean concentrations of the primary immunosuppressant were similar to treatments employed in other centres (CsA 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 concentrations 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 insulin 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 microU/ml, P=0.034). In patients with repetitive IVGTTs, glucose constant decay and insulin production 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.