Posttransplantation diabetes mellitus (PTDM) is an increasing problem in solid organ transplantation with profound impact on patient and allograft survival. One major contributing factor for the development of PTDM is choice of immunosuppression. Calcineurin inhibitors (CNIs), especially tacrolimus display a substantial diabetogenic potential but remain a cornerstone in maintenance immunosuppression for prevention of rejection and allograft loss. The diabetogenic effect of tacrolimus is mediated predominantly via disturbance of beta-cell function and impaired insulin secretion. There is growing evidence that this effect is dependent on dose and peak plasma concentrations. Once-dailyLCP-tacrolimus has been shown to have lower peak concentrations than twicedaily tacrolimus with comparable efficacy and safety.~LCP-tacrolimus has been shown to improve triglyceride levels, compared to twicedaily tacrolimus. In this study, no effect on the incidence of PTDM was observed, however assessed only by fasting plasma glucose, HbA1c and antidiabetic treatment. As 1/3 of patients with diabetes are solely diagnosed via oral glucose tolerance test, this approach is insufficient for proper evaluation of glucose metabolism, including prediabetes as the principal risk factor.~From pathophysiologic understanding blood lipids and glucose metabolism are strongly associated, as hypertriglyceridemia correlates with insulin resistance. In combination with the lower peak concentrations, it can be hypothesized that LCP-tacrolimus results in better glucose metabolism after kidney transplantation, compared to twicedaily tacrolimus Better understanding of glucose metabolism under different tacrolimus formulations would address a key component of long-term cardiovascular risk and patient outcome after kidney transplantation.
Posttransplantation diabetes mellitus after kidney transplantation mediated by tacrolimus is mainly dependent on dose and peak plasma concentration. To substantiate the potential benefits on glucose metabolism and lipid profile of LCP-tacrolimus compared to standard twice-daily tacrolimus after kidney transplantation, a prospective randomized intraindividual cross-over conversion trial with a comprehensive assessment of glucose metabolism and lipid profile is performed. Primary endpoint is the difference in insulin secretion between treatments, as the principal parameter affected by tacrolimus peak concentrations.~Aim of the study is, to assess glucose metabolism under different tacrolimus formulations (LCP-tacrolimus and twice-daily tacrolimus).