Alizadeh Dehnavi Reza, Beishuizen Edith D, van de Ree Marcel A, Le Cessie Saskia, Huisman Menno V, Kluft Cornelis, Princen Hans M G, Tamsma Jouke T
Vascular Medicine, Department of General Internal Medicine & Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands.
Eur J Intern Med. 2008 Mar;19(2):115-21. doi: 10.1016/j.ejim.2007.06.011. Epub 2007 Nov 5.
The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2.
Vascular phenotype was determined using the following endothelium-related, hemostatic, and sonographic endpoints in 62 DM2 patients with mild dyslipidemia: sVCAM, sE-selectin, von Willebrand factor (VWF), fibrinogen, s-thrombomodulin (sTM), tPA, PAI-1, flow-mediated dilation (FMD), and intima media thickness (IMT). The impact of MS load (number of criteria present), MS components, and CRP on these parameters was assessed.
Serum sVCAM, sTM, and tPA levels significantly increased with increasing MS load. IMT also significantly increased from 0.602+/-0.034 (one MS criterion) to 0.843+/-0.145 (four MS criteria, p=0.007). LogCRP significantly correlated with fibrinogen, PAI-1, and IMT. In a multiple regression (MR) model with age and gender as covariates, MS load predicted sVCAM and sTM; CRP predicted PAI-1 and fibrinogen; MS load and CRP simultaneously predicted tPA and IMT. For each MS criterion present, IMT significantly increased by 0.04 mm. An increase in CRP from 1 to 3 mg/L resulted in a significant increase of 0.04 mm. Patients with four MS criteria and inflammation (CRP >or=3 mg/L) are predicted to have a 0.21 mm thicker IMT than those without. A second stepwise MR analysis based on gender, traditional risk factors, diabetes-related parameters, renal function, individual MS criteria, and LogCRP as explanatory variables showed a significant effect of systolic and diastolic blood pressure, HDL, and LogCRP on IMT(r(2)=0.36, p<0.001).
MS and low-grade chronic inflammation have an independent impact on vascular phenotype including IMT in DM2.
2型糖尿病（DM2）患者的心血管疾病负担各不相同。我们推测代谢综合征（MS）和低度全身炎症会改变DM2患者动脉粥样硬化的程度。
在62例轻度血脂异常的DM2患者中，使用以下与内皮相关、止血和超声检查的终点指标来确定血管表型：可溶性血管细胞黏附分子（sVCAM）、可溶性E选择素、血管性血友病因子（VWF）、纤维蛋白原、可溶性血栓调节蛋白（sTM）、组织型纤溶酶原激活剂（tPA）、纤溶酶原激活物抑制剂1（PAI-1）、血流介导的血管舒张功能（FMD）和内膜中层厚度（IMT）。评估MS负荷（存在的标准数量）、MS组分和C反应蛋白（CRP）对这些参数的影响。
血清sVCAM、sTM和tPA水平随MS负荷增加而显著升高。IMT也从0.602±0.034（一项MS标准）显著增加到0.843±0.145（四项MS标准，p = 0.007）。LogCRP与纤维蛋白原、PAI-1和IMT显著相关。在以年龄和性别作为协变量的多元回归（MR）模型中，MS负荷可预测sVCAM和sTM；CRP可预测PAI-1和纤维蛋白原；MS负荷和CRP同时可预测tPA和IMT。每存在一项MS标准，IMT显著增加0.04 mm。CRP从1 mg/L增加到3 mg/L会导致IMT显著增加0.04 mm。预计有四项MS标准且伴有炎症（CRP≥3 mg/L）的患者比无炎症患者的IMT厚0.21 mm。基于性别、传统危险因素、糖尿病相关参数、肾功能、个体MS标准和LogCRP作为解释变量的第二步逐步MR分析显示，收缩压和舒张压、高密度脂蛋白（HDL）以及LogCRP对IMT有显著影响（r² = 0.36，p < 0.001）。
MS和低度慢性炎症对DM2患者的血管表型包括IMT有独立影响。
