在2型糖尿病合并微量白蛋白尿患者的厄贝沙坦研究（IRMA 2）中，内皮功能障碍和炎症可预测糖尿病肾病的发生。

Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study.

作者信息

Persson Frederik, Rossing Peter, Hovind Peter, Stehouwer Coen D A, Schalkwijk Casper G, Tarnow Lise, Parving Hans-Henrik

机构信息

Steno Diabetes Center, Gentofte, Denmark.

出版信息

Scand J Clin Lab Invest. 2008;68(8):731-8. doi: 10.1080/00365510802187226.

DOI:10.1080/00365510802187226

PMID:18609080

Abstract

OBJECTIVE

To evaluate risk factors for progression from persistent microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type 2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of endothelial dysfunction, chronic low-grade inflammation, growth factors and advanced glycation end products (AGE peptides).

METHODS

IRMA 2 was a 2-year multicentre, randomized, double-blind trial comparing irbesartan (150 and 300 mg once daily) versus placebo. The primary end-point was time to onset of diabetic nephropathy. Samples from a subgroup from the placebo and the 300 mg irbesartan treatment group were used in this post-hoc analysis (n = 269, 68 %). Nine biomarkers were analysed: high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fibrinogen, von Willebrand Factor (vWf), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin, transforming growth factor-beta (TGF-beta) and AGE peptides. Mean standard deviation scores (Z-scores) were used to combine biomarker information.

RESULTS

In a Cox enter model with combined Z-scores for biomarkers of endothelial dysfunction (vWf, sVCAM-1, sICAM-1, sE-selectin) and for biomarkers of inflammation (hs-CRP, IL-6, fibrinogen), endothelial dysfunction (hazard ratio for a 28 % increase ( = 1 SD) in Z-score) 3.20 (1.56 to 6.56), p = 0.001) and UAER (HR for a 75 % increase ( = 1 SD) in UAER) 2.61 (1.30 to 5.23), p = 0.007) were found as independent predictors. Independently, IL-6 and vWf predicted the end-point. In addition, endothelial Z-score was associated with progression of albuminuria (p = 0.038).

CONCLUSION

Endothelial dysfunction and possibly inflammation are novel predictors of progression to diabetic nephropathy in patients with type 2 diabetes and microalbuminuria independently of traditional risk factors. ClinicalTrials.gov ID: NCT00317915.

摘要

目的

在2型糖尿病合并微量白蛋白尿患者的厄贝沙坦研究（IRMA 2）中，评估从持续性微量白蛋白尿进展为糖尿病肾病的危险因素，包括内皮功能障碍、慢性低度炎症、生长因子和晚期糖基化终产物（AGE肽）的生物标志物。

方法

IRMA 2是一项为期2年的多中心、随机、双盲试验，比较厄贝沙坦（每日150和300毫克）与安慰剂。主要终点是糖尿病肾病的发病时间。在这项事后分析中使用了来自安慰剂组和300毫克厄贝沙坦治疗组的一个亚组的样本（n = 269，68%）。分析了九种生物标志物：高敏C反应蛋白（hs-CRP）、白细胞介素6（IL-6）、纤维蛋白原、血管性血友病因子（vWf）、可溶性血管细胞粘附分子-1（sVCAM-1）、可溶性细胞间细胞粘附分子-1（sICAM-1）、sE-选择素、转化生长因子-β（TGF-β）和AGE肽。使用平均标准差分数（Z分数）来整合生物标志物信息。

结果

在一个Cox进入模型中，对于内皮功能障碍生物标志物（vWf、sVCAM-1、sICAM-1、sE-选择素）和炎症生物标志物（hs-CRP、IL-6、纤维蛋白原）的综合Z分数，发现内皮功能障碍（Z分数增加28%（=1个标准差）的风险比）为3.20（1.56至6.56），p = 0.001）和尿白蛋白排泄率（UAER增加75%（=1个标准差）的风险比）为2.61（1.30至5.23），p = 0.007）是独立预测因素。独立地，IL-6和vWf预测了终点。此外，内皮Z分数与白蛋白尿的进展相关（p = 0.038）。