Insulin Hyposecretion in Nondiabetic, Tacrolimus-Treated Renal Transplant Recipients More Than 6 months Posttransplantation

Abstract

New-onset diabetes after transplantation is an important complication of renal transplantation. Few studies have examined nondiabetic renal transplant recipients for occult defects in insulin sensitivity or secretion. The aims of this study were to identify abnormalities of glucose metabolism in nondiabetic, tacrolimus-treated renal transplant recipients more than 6 months posttransplantation and characterize determinants. Eighteen nondiabetic renal transplant recipients and 20 healthy control subjects were examined with a frequently sampled intravenous glucose tolerance test and meal tolerance test to derive first-phase insulin secretion (FPIR), insulin sensitivity, and second-phase insulin secretion. FPIR was higher in controls compared with transplant recipients (2225 vs. 1173 pmol/L; P=0.003). In transplant subjects, there was a strong positive linear correlation between glomerular filtration rate (GFR) and FPIR (Pearson correlation r=0.7; P=0.002). There were strong negative correlations between trough tacrolimus concentration at study entry (r=-0.56; P=0.01) and 3-month tacrolimus exposure (r=-0.49; P=0.02) with GFR, but not with FPIR. Nondiabetic renal transplant recipients had lower FPIR than controls with normal renal function. Declining FPIR predicts type 2 diabetes in the general population. Interpreting the relationship between FPIR and GFR requires exploration of dual tacrolimus toxicity on both renal and pancreatic beta-islet cell function.