Regulation of glucose tolerance in patients after liver transplantation - Impact of cyclosporin versus tacrolimus therapy

Background. We investigated the factors regulating glucose homeostasis in 1 0 healthy (control) subjects, as well as in stable, long-term, liver-grafte d patients receiving monotherapy in the form of either cyclosporin A (n=10) or tacrolimus (n=10). Methods. We measured insulin sensitivity, first- and second-phase insulin s ecretion, with a minimal modeling technique based on the analysis of glucos e, insulin, and C-peptide profiles during frequently sampled intravenous gl ucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT. Results. Glucose and insulin concentrations before and after glucose loadin g did not differ in liver transplant patients and in control subjects. Fast ing C-peptide levels in both liver-grafted groups were higher than in healt hy subjects and remained elevated during FSIGTT (P<0.05). Intravenous gluco se tolerance [(K-G), i.e. the slope of the regression of logarithm of the b lood glucose concentrations vs. time], insulin sensitivity, and first phase insulin secretion did not differ in Liver grafted groups and healthy subje cts. Second-phase insulin secretion was about 56% higher in liver-grafted p atients than in controls (P<0.05). Body mass index was the overall determin ant of insulin sensitivity in all groups. Conclusions. Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitiv ity (posthepatic insulin effect) and enhanced second-phase insulin secretio n (prehepatic insulin) point to an accelerated hepatic insulin clearance ra te in liver transplant patients. Increased hepatic insulin clearance is com pensated by enhanced insulin secretion, indicating that insulin clearance i s the major determinant of pancreatic function in liver-grafted patients.