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接受他克莫司治疗的成年肾移植受者发生移植后糖尿病的临床和遗传危险因素。

Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus.

作者信息

Numakura Kazuyuki, Satoh Shigeru, Tsuchiya Norihiko, Horikawa Yohei, Inoue Takamitsu, Kakinuma Hideaki, Matsuura Shinobu, Saito Mitsuru, Tada Hitoshi, Suzuki Toshio, Habuchi Tomonori

机构信息

Department of Urology, Akita University School of Medicine, Akita, Japan.

出版信息

Transplantation. 2005 Nov 27;80(10):1419-24. doi: 10.1097/01.tp.0000181142.82649.e3.

Abstract

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 pharmacokinetics 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 polymorphisms 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.

摘要

背景

本研究调查了移植后糖尿病(PTDM)的发病率,并根据临床特征、他克莫司药代动力学以及与他克莫司药代动力学或糖尿病相关的基因多态性,计算了在基于他克莫司的免疫抑制治疗下发生PTDM的风险。

方法

对70例非糖尿病成年肾移植受者进行了研究。术后6个月移植后连续3个月以上血糖水平持续升高、糖化血红蛋白A1c超过6.5mg/dl或需要胰岛素和/或口服降糖药的患者被诊断为患有PTDM。评估了12种基因多态性。

结果

移植后6个月,10例受者(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率、总类固醇剂量、他克莫司药代动力学或其与基因多态性的相关性方面无显著差异。维生素D受体(VDR)TaqI t等位基因患者的PTDM发生率显著高于TT基因型患者(P=0.013)。多因素分析显示,年龄超过50岁(比值比9.28,P=0.003)和存在VDR TaqI t等位基因(比值比7.05,P=0.048)与PTDM的发生相关。

结论

我们队列中PTDM的发生率为14.3%。年龄超过50岁是一个危险因素。VDR TaqI t等位基因的存在也可能是PTDM的一个危险因素,这表明对糖尿病相关多态性进行基因分型可能是预测患者发生PTDM风险的一种方法,并且在为个体选择合适的免疫抑制方案方面将是一项有价值的资产。

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