Clinical And Genetic Risk Factors For Posttransplant Diabetes Mellitus In Renal Transplant Recipients Treated With Tacrolimus

Background. Posttransplant diabetes mellitus (PTDM), a common complication of kidney transplantation, adversely affects graft function and survival, cardiovascular morbidity and mortality, quality of life. At present a number of clinical characteristics have been identified that appear to predispose patients to the development of PTDM, such as age, family history, patient body weight. Moreover, recent clinical experiences with tacrolimus (FK506) suggested that the higher incidence of PTDM may have been associated with higher doses and higher blood trough levels of FK506. With respect to gene polymorphism:FK506 is recognized to be a substrate of cytochrome P450 (CYP) 3A5 encoded by CYP3A5, which may influence individual variations in FK506 pharmacokinetics; epidemiological studies in human beings consistently show that low blood concentrations of 25-hydroxyvitamin D (25[OH]D, a marker of vitamin D status) influenced by CYP24A1 are associated with an increased risk of type 2 diabetes; the peroxisome proliferator-activated receptor-gamma (PPAR-γ) gene involved in glucose and lipid homeostasis can influence insulin sensitivity. The purpose of this study was to assess the incidence of posttransplant diabetes mellitus (PTDM) and to establish the influence of different risk factors on the development of PTDM under a tacrolimus-based immunosuppression in accordance with clinical characteristics and genetic polymorphisms related to tacrolimus pharmacokinetics or diabetes mellitus.Methods. We examined 129 non-diabetic adult recipients in Qianfoshan hospital with no history of earlier glucose metabolism disorders who received their first kidney transplantation between September 2011 and December 2014 under FK506-based immunosuppression, like Gender, age, dialysis duration, body mass index (BMI), cytomegalovirus infection, dose of steroid and FK506, concentration of FK506 and polymorphisms related to tacrolimus pharmacokinetics or diabetes mellitus. and the time since renal transplantation were recorded. The chi-square test and Logistic regression was used to assess the influence of each risk factor on the development of PTDM. PTDM was diagnosed on basis of fasting plasma glucose (FPG) and oral glucose tolerance tests (OGTTs) in normal FPG recipients.Results. Six months later, we diagnosed 17 recipients developing PTDM among 129 patients. The incidence of newly diagnosed PTDM in the present study was 13.2%. There were no significant differences in acute rejection, dialysis duration, Cytomegalovirus infection, tacrolimus pharmacokinetics and its related to genetic polymorphisms between the two groups. Multivariate analysis identified age over 50 years old (OR=5.135, P=0.005) and the presence of the CYP24A1 rs2296241 A allele (OR=7.011, P=0.016) were correlated with the development of PTDM.Conclusions. Patients with higher age (especially over 50 years old) and the CYP24A1 rs2296241 A allele had an increased risk of PTDM after kidney transplantation, suggesting that genotyping of diabetes-related polymorphisms may be valuable to screen for development of PTDM.