Tacrolimus reversibly reduces insulin secretion in paediatric renal transplant recipients

Nephrol Dial Transplant. 2000 Jun;15(6):867-71. doi: 10.1093/ndt/15.6.867.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Child
  • Creatinine / blood
  • Cyclosporine / therapeutic use
  • Glomerular Filtration Rate / drug effects
  • Glucose Tolerance Test
  • Glycated Hemoglobin A / analysis
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology*
  • Prednisolone / therapeutic use
  • Tacrolimus / therapeutic use*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Immunosuppressive Agents
  • Insulin
  • Cyclosporine
  • Prednisolone
  • Creatinine
  • Tacrolimus