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转化生长因子β 1 作为糖尿病周围神经病变的生物标志物:横断面研究。

Transforming growth factor beta 1 as a biomarker of diabetic peripheral neuropathy: cross-sectional study.

机构信息

Instituto de Cardiología Avanzada (ICAMED), Centro Medico Teknon, Barcelona, Spain.

出版信息

J Diabetes Complications. 2010 Sep-Oct;24(5):306-12. doi: 10.1016/j.jdiacomp.2009.07.007. Epub 2009 Sep 30.

Abstract

BACKGROUND

Simple and efficient screening methods are lacking for diabetic peripheral neuropathy (DPN), the most common and most difficult to treat of the long-term diabetic complications. Increased levels of transforming growth factor beta 1 (TGFbeta1) in type 2 diabetic patients (T2DM) plays an immunomodulatory role in diabetic nephropathy and, possibly, in atherosclerotic evolution. Since preliminary interrelationships between experimental DPN and TGFbeta1 have been observed, we sought to assess whether TGFbeta1 could be a biomarker molecule for human DPN.

MATERIALS AND METHODS

Cross-sectional cohort study focused on the assessment of the interrelationships between TGFbeta1 levels, cardiovascular disease (CVD), diabetic nephropathy (DNF), and neuropathy (DPN) in a group of T2DM patients (N=180; male 117, female 63) randomly selected from the North Catalonia Diabetes Study. DPN was diagnosed using clinical and neurophysiology evaluation. Incipient DNF was assessed by microalbuminuria (MAU). Total TGFbeta1 (without acidification) was measured by immunoassay by ELISA (Promega).

RESULTS

DPN correlated with age, time of diabetes duration, MAU, CVD, and TGFbeta1 (P<.0001). Log-transformed TGFbeta1 (logTGbeta1) was significantly higher in patients with DPN than in those without (P<.0005). LogTGFbeta1 (OR=7.5; P=.006), age (OR=1.1; P<.0005), and logMAU (OR=2.0; P=.016) appear as significant estimators of the occurrence of DPN in our series. The integrated ROC curve evaluation with these three parameters expressed an important sensitivity (78.1%), specificity (76.0%), positive predictive value (79.2%), and negative predictive value (70.3%) in relation to DPN presence.

DISCUSSION

TGFbeta1 stands as an important biomarker molecule for DFN and DPN screening in our series. Further prospective studies are warranted.

摘要

背景

简单有效的筛查方法对于糖尿病周围神经病变(DPN)来说是缺乏的,这是糖尿病长期并发症中最常见和最难治疗的一种。在 2 型糖尿病患者(T2DM)中,转化生长因子β 1(TGFβ1)水平升高在糖尿病肾病中发挥免疫调节作用,并且可能在动脉粥样硬化的演变中发挥作用。由于已经观察到实验性 DPN 与 TGFβ1 之间存在初步的相互关系,我们试图评估 TGFβ1 是否可以成为人类 DPN 的生物标志物分子。

材料和方法

这是一项横断面队列研究,重点评估了 TGFβ1 水平与心血管疾病(CVD)、糖尿病肾病(DNF)和神经病变(DPN)之间的相互关系,研究对象为随机选自北加泰罗尼亚糖尿病研究的一组 T2DM 患者(N=180;男性 117 例,女性 63 例)。DPN 通过临床和神经生理学评估进行诊断。微量白蛋白尿(MAU)用于评估早期 DNF。总 TGFβ1(未经酸化)通过 ELISA(Promega)的免疫测定法进行测量。

结果

DPN 与年龄、糖尿病病程时间、MAU、CVD 和 TGFβ1 相关(P<.0001)。患有 DPN 的患者的 logTGFβ1(logTGβ1)显著高于未患有 DPN 的患者(P<.0005)。在我们的研究系列中,logTGFβ1(OR=7.5;P=.006)、年龄(OR=1.1;P<.0005)和 logMAU(OR=2.0;P=.016)似乎是 DPN 发生的重要预测因子。用这三个参数进行的综合 ROC 曲线评估在与 DPN 存在相关时表达了重要的敏感性(78.1%)、特异性(76.0%)、阳性预测值(79.2%)和阴性预测值(70.3%)。

讨论

在我们的研究系列中,TGFβ1 是 DFN 和 DPN 筛查的重要生物标志物分子。需要进一步的前瞻性研究。

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