Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus
Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus
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DOI：
10.1097/01.tp.0000181142.82649.e3
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发表时间：
2005-11-27
期刊：
影响因子：
6.2
通讯作者：
Habuchi, T
中科院分区：
文献类型：
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作者：
Numakura, K;Satoh, S;Habuchi, T
背景。本研究调查了移植后糖尿病（PTDM）的发生率，并根据临床特征、他克莫司药代动力学以及与他克莫司危害动力学或糖尿病相关的遗传多态性计算了他克莫司免疫抑制下发生PTDM的风险。对70名非糖尿病成人肾受体进行了研究。患者持续高血糖水平，超过6.5 mg/dl的糖化血红蛋白，或移植术后6个月后需要胰岛素和/或口服降糖药超过3个月诊断为PTDM。对12个基因组多态性进行了评估。移植后6个月，10名受者（14.3%）发生PTDM。阳性危险因素为年龄（P=0.019）和体重指数（P=0.038）。两组在急性排斥反应发生率、类固醇总剂量、他克莫司药代动力学及其与遗传多态性的相关性方面均无显著差异。维生素D受体（VDR） TaqI - t等位基因患者发生PTDM的频率明显高于TT基因型患者（P=0.013）。多因素分析显示，年龄大于50岁（比值比9.28，P=0.003）和VDR TaqI等位基因的存在（比值比7.05，P=0.048）与ptdm的发生相关。我们的队列中PTDM的发病率为14.3%。年龄超过50岁是一个危险因素。VDR TaqI等位基因的存在也可能是PTDM的一个危险因素，这表明糖尿病相关多态性的基因分型是预测患者发生PTDM风险的一种可能方法，并且将是为个体选择合适的免疫抑制方案的宝贵资产。
Background. The present study investigated the incidence of posttransplant diabetes mellitus (PTDM) and calculated the risk of developing PTDM under a tacrolimus-based immunosuppression based on clinical characteristics, tacrolimus pharmacokinetics, and genetic polymorphisms related to tacrolimus p harm acokinetics or diabetes mellitus.Methods. Seventy nondiabetic adult kidney recipients were studied. Patients with continuous high plasma glucose levels, over 6.5 mg/dl of hemoglobin A1c, or requiring insulin and/or oral antidiabetic agents for more than 3 months after transplantation 6 months postoperatively were diagnosed as having PTDM. Twelve genomic polymorphisms were assessed.Results. Six months after transplantation, 10 recipients (14.3%) developed PTDM. Positive risk factors were age (P=0.019) and body mass index (P=0.038). There were no significant differences in acute rejection rate, total steroid doses, tacrolimus pharmacokinetics or its related to genetic polymorpbisnis between the two groups. The frequency of PTDM was significantly higher in patients with the vitamin D receptor (VDR) TaqI t allele than in those with the TT genotype (P=0.013). On multivariate analysis, age over 50 years (odds ratio 9.28, P=0.003) and the presence of the VDR TaqI t allele (odds ratio 7.05, P=0.048) were correlated with the development of PTDM.Conclusion. The incidence of PTDM was 14.3% in our cohort. Age over 50 years was a risk factor. The presence of the VDR TaqI t allele may also be a risk factor for PTDM, suggesting that genotyping of diabetes-related polymorphisms is a possible method of predicting a patient's risk for developing PTDM and would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals.