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.
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.
Authors: J Zhang; H K Takahashi; K Liu; H Wake; R Liu; H Sadamori; H Matsuda; T Yagi; T Yoshino; S Mori; M Nishibori Journal: Br J Pharmacol Date: 2010-07 Impact factor: 8.739
Authors: Pauline Lancia; Tiphaine Adam de Beaumais; Valéry Elie; Florentine Garaix; Marc Fila; François Nobili; Bruno Ranchin; Pascale Testevuide; Tim Ulinski; Wei Zhao; Georges Deschênes; Evelyne Jacqz-Aigrain Journal: Pediatr Nephrol Date: 2018-02-04 Impact factor: 3.714
Authors: Deidre Jansson; Andy Cheuk-Him Ng; Accalia Fu; Chantal Depatie; Mufida Al Azzabi; Robert A Screaton Journal: Proc Natl Acad Sci U S A Date: 2008-07-14 Impact factor: 11.205