Influence of tacrolimus on glucose metabolism before and after renal transplantation: a prospective study

Abstract

Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (k(G)), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, k(G) was indeterminate in three patients. During tacrolimus, k(G) decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P<0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU x min/L to 558.0 mU x min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal k(G). During tacrolimus administration, k(G) decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate k(G) seem to be at risk of developing PTDM while on tacrolimus.