Related Experiment Videos
Tacrolimus reversibly reduces insulin secretion in paediatric renal transplant recipients
G Filler1, I Neuschulz, I Vollmer
1Department of Paediatric Nephrology, Charité Children's Hospital, Berlin, Germany.
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.
Insights
Tacrolimus (FK506) may cause post-transplant diabetes by directly impairing pancreatic beta cell function. Reducing tacrolimus dosage can improve glucose tolerance and insulin production in transplant patients.
Area of Science:
- Nephrology
- Endocrinology
- Immunology
Background:
- Conflicting reports exist regarding the mechanism of tacrolimus-induced post-transplant diabetes mellitus.
- Understanding this mechanism is crucial for managing transplant recipients.
Purpose of the Study:
- To investigate the mechanism of tacrolimus (FK506) induced post-transplant diabetes mellitus.
- To compare glucose tolerance and pancreatic beta cell function in pediatric renal transplant recipients on tacrolimus versus cyclosporine.
Main Methods:
- Intravenous glucose tolerance tests (IVGTT) were performed on 14 pediatric renal transplant recipients on cyclosporine (CsA) microemulsion and 15 on tacrolimus (FK506).
- Parameters analyzed included glucose, insulin, C-peptide concentrations, and HbA1c.
- Patient groups were matched for age, BMI, serum creatinine, time post-transplant, and cumulative steroid dose.
Main Results:
- Baseline glucose concentrations were significantly higher in the tacrolimus group compared to the cyclosporine group.
- Insulin and C-peptide concentrations were similar at baseline between groups.
- Tacrolimus trough levels correlated negatively with glucose decay rates (k values).
- A significant reduction in first-phase insulin secretion was observed in the tacrolimus group.
- Lowering tacrolimus dosage improved glucose decay and insulin production in patients with repeat IVGTTs.
Conclusions:
- Post-transplant glucose intolerance associated with tacrolimus may result from a dose-dependent, direct effect on pancreatic beta cell function.
- Dose reduction of tacrolimus can potentially manage or improve this glucose intolerance.