Influence of conversion from cyclosporine A to tacrolimus on insulin sensitivity assessed by euglicaemic hyperinsulinemic clamp technique in patients after kidney transplantation.

Background: Recent studies have shown diabetogenic properties of calcineurin inhibitors, but the mechanism of more pronounced diabetogenic effect of tacrolimus (TAC) has not been completely elucidated. The study was designed to answer 2 questions: Does conversion from CyA to TAC influence tissue insulin sensitivity in patients after kidney transplantation? Are there any additional factors influencing insulin sensitivity in these patients?

Material/methods: Fifteen non-diabetic kidney transplant recipients, receiving CyA-based regimen were recruited to the study. Enrolled patients required conversion to TAC-based treatment due to CyA adverse effects. Euglicaemic-hyperinsulinemic clamp was performed shortly before and 3 months after conversion from CyA to TAC.

Results: Two out of 15 patients developed PTDM shortly after conversion. Mean insulin sensitivity indices: glucose cell uptake (M value) and glucose cell uptake to insulin plasma concentration ratio (M/I) did not change significantly after 3 months of TAC treatment compared to initial values. Significant negative correlations between increase of body mass and both: changes of M values (-0.576; p=0.02) and M/I ratios (-0.819; p<0.001) were observed. Similar correlations were observed between changes of BMI and M values (-0.575; p=0.02) or M/I ratios (-0.800; p<0.001). A significant positive correlation between changes of eGFR values and M/I ratios (0.591; p=0.03) was noted.

Conclusions: Tissue insulin sensitivity estimated by hyperinsulinemic, euglycaemic clamp technique did not change significantly after conversion from CyA to TAC therapy in patients after kidney transplantation. Weight gain and eGFR decrease are associated with decrease of insulin sensitivity in these patients.