Glucose Metabolism in Renal Transplant Recipients on Tacrolimus: The Effect of Steroid Withdrawal and Tacrolimus Trough Level Reduction

Abstract

The relative role of steroids and tacrolimus in the development of glucose metabolic disorders and hyperlipidemia after renal transplantation has not yet been clearly established. Therefore, glucose metabolism was prospectively evaluated by intravenous glucose tolerance test, as was lipid profile, in fifteen white nondiabetic renal transplant recipients three times: before and after steroid withdrawal and after tacrolimus trough level reduction. After withdrawal of 10 mg of prednisolone, insulin resistance decreased (fasting C-peptide, 0.99 to 0.77 nmol/L [P < 0.0009]; fasting insulin, 9.5 to 8.1 mU/L [P = 0.09]; insulin/glucose ratio, 1.85 to 1.45 mU/mmol [P = 0.10]) and lipid levels decreased (total cholesterol, 5.1 to 4.2 mmol/L [P = 0.006]); HDL cholesterol, 1.4 to 1.1 mmol/L [P = 0.01]; LDL cholesterol, 3.0 to 2.5 mmol/L [P = 0.15]; triglycerides, 1.52 to 0.91 mmol/L [P = 0.02]). After tacrolimus trough level reduction from 9.5 to 6.4 ng/ml, pancreatic beta-cell secretion capacity improved (C-peptide secretion increased from 49.0 to 66.6 nmol x min/L [P = 0.04] and insulin secretion increased from 1134 to 1403 mU x min/L [P = 0.06]). HbA1c improved also, from 5.9 to 5.3% (P = 0.002). Lipids did not change. In conclusion, steroid withdrawal resulted in a decrease in insulin resistance and a reduction in lipids, and tacrolimus trough level reduction resulted in an improved pancreatic beta-cell secretion capacity. Therefore, these therapeutic measurements may contribute to the reduction of the cardiovascular morbidity and mortality in renal transplant recipients.