IntroductionDespite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization.MethodsWe conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein–cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months.ResultsThe study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2–12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8–8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms.ConclusionIn high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.

Background Post-transplant prediabetes (PreDM) and diabetes (PTDM) are common and have an impact on cardiovascular events. We sought to investigate the pathogenesis and best approach for prediction. Methods We prospectively studied 115 waitlisted patients from a single center without manifest diabetes. An oral glucose tolerance test (OGTT) was performed yearly until transplantation and 12 months later. Insulin secretion, insulin sensitivity (IS), and disposition index (DI) were derived from the OGTT. Results PreDM and PTDM were observed in 27% and 28.6% of patients, respectively. Pretransplant age, BMI, 120 mn glucose, IS, DI, and prediabetes or undiagnosed diabetes were significantly associated with these alterations. In multivariate analysis, pretransplant age (OR 1.5; 95% CI 1.04–2.1), BMI (OR 1.16; 95% CI 1.04–1.3), and cumulative steroids (OR 1.5; 95% CI 1.02–2.2) were predictors of PreDM or PTDM. ROC curve analysis showed that pretransplant BMI and 120 mn glucose had the highest AUC (0.72; 95% CI 0.62–0.8; and 0.69; 95% CI 0.59–0.79, respectively). The highest discrimination cut-off for BMI (≥28.5 Kg/m2) and 120 mn glucose (≥123.5 mg/dl) yielded similar number needed to diagnose (2.5). Conclusions PreDM or PTDM develops in waitlisted patients with an ineffective insulin secretion and BMI shows a similar diagnostic capacity to OGTT. Pretransplant interventions may reduce post-transplant glucose alterations.