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低剂量类固醇对非糖尿病肾移植受者长期随访中糖化血红蛋白(HbA1c)水平、糖尿病前期及新发性糖尿病(NODAT)发生发展的影响

Impact of low-dose steroids on HbA1c levels and development of pre-diabetes and NODAT in non-diabetic renal transplant recipients on long-term follow-up.

作者信息

Tillmann F P, Schmitz M, Rump L C, Quack I

机构信息

Klinik für Nephrologie, Heinrich Heine Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.

Klinik für Nephrologie und allgemeine innere Medizin, städtisches Klinikum Solingen, Gotenstraße 1, 42653, Solingen, Germany.

出版信息

Int Urol Nephrol. 2018 Apr;50(4):771-777. doi: 10.1007/s11255-017-1754-0. Epub 2017 Dec 2.

Abstract

BACKGROUND

This study aimed to evaluate the impact of 5 mg of prednisolone/day on HbA1c levels and its association with the development of pre-diabetes and new-onset diabetes mellitus (NODAT) in non-diabetic first renal transplant recipients on long-term follow-up.

METHODS

Four hundred patients were analysed on an average of 4.1 ± 3.0 years after successful transplantation: 96 (24%) were steroid-free and 304 (76%) treated with 5 mg of prednisolone/day combined with cyclosporine A (CsA) or tacrolimus (Tac) as part of their immunosuppressive protocol. Pre-diabetes and NODAT were defined based on the HbA1c levels according to the current ADA guidelines. The Mann-Whitney U test and the Chi-square test were used to determine intergroup differences. Multivariate logistic regression analyses (adjusted for steroid-free versus 5 mg of prednisolone per day, body mass index (BMI), number of HLA mismatches, eGFR according to the CKD-EPI formula, sex, negative vs. positive PRA titre, CMV and HCV positivity of the recipient, CsA vs. Tac immunosuppressive medication, dialysis vintage (years), age at the last follow-up and time from transplantation to the last follow-up) were performed to identify an independent effect of low-dose steroids on the evolution of pre-diabetes and NODAT.

RESULTS

A small but statistically significant difference in HbA1c levels was observed between the control and the steroid groups (5.56 ± 0.54 vs. 5.67 ± 0.0.45%, p = 0.045). The incidence rates of pre-diabetes and NODAT per 100 patients per year were 9.3 and 3.0, respectively. Regression analysis showed that low-dose steroids (p = 0.026, risk ratio (RR) 1.789, 95%; confidence interval (CI) 1.007-3.040) and age (p = 0.000, RR 1.037/year, 95% CI 1.018-1.057) were associated with pre-diabetes, whereas BMI (p = 0.000, RR 1.190, 95% CI 1.084-1.307), age (p = 0.000, RR 1.087/year, 95% CI 1.047-1.129) and Tac use (p = 0.010, RR 3.300, 95% CI 1.328-8.196) were associated with NODAT.

CONCLUSION

Using 5 mg of prednisolone/day was associated with increased HbA1c levels and an increased risk in developing pre-diabetes, but not NODAT, whereas BMI, age and the use of tacrolimus were associated with an increased risk in developing NODAT.

摘要

背景

本研究旨在评估非糖尿病初发肾移植受者长期随访期间,每日服用5毫克泼尼松龙对糖化血红蛋白(HbA1c)水平的影响,及其与糖尿病前期和新发糖尿病(NODAT)发生的相关性。

方法

对400例患者进行分析,这些患者在成功移植后平均随访4.1±3.0年:其中96例(24%)未使用类固醇,304例(76%)作为免疫抑制方案的一部分,每日服用5毫克泼尼松龙并联合环孢素A(CsA)或他克莫司(Tac)。根据美国糖尿病协会(ADA)现行指南,依据HbA1c水平定义糖尿病前期和NODAT。采用曼-惠特尼U检验和卡方检验确定组间差异。进行多因素逻辑回归分析(针对未使用类固醇与每日服用5毫克泼尼松龙、体重指数(BMI)、HLA错配数、根据慢性肾脏病流行病学协作组(CKD-EPI)公式计算的估算肾小球滤过率(eGFR)、性别、群体反应性抗体(PRA)滴度阴性与阳性、受者的巨细胞病毒(CMV)和丙型肝炎病毒(HCV)阳性情况、CsA与Tac免疫抑制药物、透析时间(年)、末次随访时的年龄以及从移植到末次随访的时间进行校正),以确定低剂量类固醇对糖尿病前期和NODAT进展的独立影响。

结果

在对照组和类固醇组之间观察到HbA1c水平存在微小但具有统计学意义的差异(5.56±0.54对5.67±0.45%,p=0.045)。糖尿病前期和NODAT的年发病率分别为每100例患者9.3例和3.0例。回归分析表明,低剂量类固醇(p=0.026,风险比(RR)1.789,95%;置信区间(CI)1.007 - 3.040)和年龄(p=0.000,RR 1.037/年,95% CI 1.018 - 1.057)与糖尿病前期相关,而BMI(p=0.000,RR 1.190,95% CI 1.084 - 1.307)、年龄(p=0.000,RR 1.087/年,95% CI 1.047 - 1.129)和使用Tac(p=0.010,RR 3.300,95% CI 1.328 - 8.196)与NODAT相关。

结论

每日服用5毫克泼尼松龙与HbA1c水平升高以及糖尿病前期发生风险增加相关,但与NODAT无关,而BMI、年龄和使用他克莫司与NODAT发生风险增加相关。

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