Department of Nephrology, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
Nephrol Dial Transplant. 2012 Aug;27(8):3330-7. doi: 10.1093/ndt/gfs020. Epub 2012 Apr 6.
After renal transplantation, patients are prone to develop impairments in glucose metabolism. In 2005, the American Diabetes Association published new guidelines on the diagnosis of pre-diabetes [plasma glucose levels from 100 to 125 mg/dL fasting or from 140 to 199 mg/dL 2 h after an oral glucose tolerance test (OGTT)]. This study sought to evaluate the prevalence and the potentially associated factors of pre-diabetes in a cohort of renal transplant patients on maintenance immunosuppressive medication. Furthermore, the diagnostic value of HbA1-c measurements in predicting pre-diabetes in transplant patients is undetermined.
Two hundred consecutive renal transplant patients of our outpatient transplant clinic were evaluated using a standard OGTT. On the day of testing, multiple factors presumably associated with pre-diabetes were assessed via a standardized questionnaire: daily steroid dosage, triglyceride levels, cholesterol levels, estimated glomerular filtration rate (eGFR) [abbreviated Modification of Diet in Renal Disease (MDRD) formula], systolic and diastolic blood pressure, pulse pressure, age, gender, body mass index (BMI), BMI <>30 and <>25, number of renal transplants, number of rejection episodes prior to testing, source of renal transplant, cause of renal failure and medications as related to the prescription of cyclosporine, tacrolimus, mycophenolate mophetil, angiotensin-converting enzyme inhibitors, AT1-blockers, statins, β-blockers and thiazide diuretics. Patients diagnosed with pre-diabetes were compared to subjects with normal test results. Fishers exact test and the Wilcoxon rank-sum test were applied to compare the two study populations, whereas multivariate logistic regression was used to seek potential risk factors as related to other covariates. Risk ratios (RRs) to develop pre-diabetes were calculated for significant variables.
Ten patients had results indicative of post-transplant diabetes whereas data sets of three other patients were incomplete and were thus not included in the analysis. From the remaining 187 patients, 130 (69.5%) displayed normal test results whereas 57 (30.5%) had results indicative of pre-diabetes. On multivariate regression analysis, patients with pre-diabetes were significantly older {55.3 ± 12.1 versus 47.7 ± 12.6 years, P = 0.0007, RRs per 5 years increase 1.28 [95% confidence interval (95% CI) 1.11-1.47]}, had more rejection episodes [0.26 ± 0.48 versus 0.12 ± 0.37, P = 0.0024, RRs per rejection episode 3.99 (95% CI 1.63-9.77)] and showed lower diastolic blood pressure readings [77 ± 10 mmHg versus 81 ± 10 mmHg, P = 0.0362, RR per 5 mmHg decrease 1.14 (95% CI 1.04-1.49)].
There is a high incidence of latent pre-diabetes among renal transplant recipients. Increasing age, rejection episodes and lower diastolic blood pressure proved to be associated with pre-diabetes. In contrast to post-transplant diabetes, tacrolimus use and HbA1-c levels were not prognostic of pre-diabetes.
肾移植后,患者易发生葡萄糖代谢受损。2005 年,美国糖尿病协会发布了新的糖尿病前期诊断指南[空腹时血浆葡萄糖水平 100-125mg/dL 或口服葡萄糖耐量试验(OGTT)后 2 小时 140-199mg/dL]。本研究旨在评估维持免疫抑制药物治疗的肾移植患者队列中糖尿病前期的患病率及其潜在相关因素。此外,HbA1-c 测量在预测移植患者糖尿病前期方面的诊断价值尚未确定。
我们对我院门诊移植诊所的 200 例连续肾移植患者进行了评估,采用标准 OGTT。在测试日,通过标准化问卷评估与糖尿病前期相关的多种因素:每日类固醇剂量、甘油三酯水平、胆固醇水平、估计肾小球滤过率(eGFR)[简化肾脏病饮食改良公式(MDRD)]、收缩压和舒张压、脉压、年龄、性别、体重指数(BMI)、BMI<>30 和<>25、肾移植次数、测试前排斥反应次数、肾移植来源、肾功能衰竭原因以及与环孢素、他克莫司、吗替麦考酚酯、血管紧张素转换酶抑制剂、AT1 受体阻滞剂、他汀类药物、β-受体阻滞剂和噻嗪类利尿剂处方相关的药物。将诊断为糖尿病前期的患者与正常检测结果的患者进行比较。Fisher 确切检验和 Wilcoxon 秩和检验用于比较两组研究人群,而多变量逻辑回归用于寻找与其他协变量相关的潜在危险因素。为显著变量计算发展为糖尿病前期的风险比(RR)。
10 例患者的检测结果提示为移植后糖尿病,另有 3 例患者的数据集不完整,因此未纳入分析。在剩余的 187 名患者中,130 名(69.5%)检测结果正常,57 名(30.5%)检测结果提示为糖尿病前期。多变量回归分析显示,糖尿病前期患者的年龄明显较大[55.3±12.1 岁比 47.7±12.6 岁,P=0.0007,每增加 5 岁 RR 为 1.28(95%置信区间[95%CI]为 1.11-1.47)],排斥反应次数更多[0.26±0.48 次比 0.12±0.37 次,P=0.0024,RR 为每例排斥反应 3.99(95%CI 为 1.63-9.77)],舒张压读数较低[77±10mmHg 比 81±10mmHg,P=0.0362,RR 为每降低 5mmHg 为 1.14(95%CI 为 1.04-1.49)]。
肾移植受者中存在较高的潜在糖尿病前期发生率。年龄增长、排斥反应和较低的舒张压与糖尿病前期相关。与移植后糖尿病不同,他克莫司的使用和 HbA1-c 水平与糖尿病前期无关。