Lower deleterious diabetogenic effect of low concentration tacrolimus on Chinese Han people / 中华器官移植杂志

ABSTRACT

Objective To elucidate the deleterious diabetogenic effect of tacrolimus on Chinese Han people.Methods According to patients' whole blood trough levels,the concentration of tacroli- mus was 5,15 and 25?g/L.Human islet cells cultured in vitro were exposed to various concentra- tions of tacrolimus for 72 h respectively,then stimulated by glucose at low (2.8 mmol/L) and high (16.7 mmol/L) levels.Glucose-stimulating insulin secretion during subsequent static incubation was measured using the ultrasensitive human insulin ELISA kit.The assessment of islet cell viability was studied with acridine orange (AO)-propidium iodide (PI).According to fasting plasma glucose,461 subjects were divided into normal glucosetolerance group (FPG＜5.55 mmol/L),impaired fasting glu- cose group (5.55 mmol/L＜FPG＜6.88 mmol/L) and posttransplant diabetes mellitus group (FPG≥6.89 mmol/L).A retrospective review of 461 non-diabetic kidney recipients completing at least 12 months of follow-up was performed to determine risk factors,incidence,and characteristics of post- transplant diabetes mellitus (PTDM).Results In vitro,lower tacrolimus concentration had not dele- terious effect on insulin secretion and viability of islet;high tacrolimus impaired?-cell survival as well as insulin secretion.Of the 461 patients with no history of diabetes at transplantation over the study period of 12 months,123 received tacrolimus and 338 received cyclosporine A (CsA).For patients receiving tacrolimus the cumulative incidence of PTDM was 13.8%,compared with 7.7% for pa- tients receiving CsA,showing no significant difference between them.The reduced tacrolimus level within the therapeutic window resulted in an increase in better glucose metabolism.Older age,family history of diabetes,acute rejection episodes and pre-transplant impaired fasting glucose were identified as risk factors for PTDM.Conclusion The diabetogenic effect of TAC is dose-dependent,and in the majority is reversible.Low initial doses,more rapidly tapering and lower maintenance levels of tacroli- mus decrease the incidence of PTDM in patients receiving tacrolimus.