Naka Katerina K, Papathanassiou Katerina, Bechlioulis Aris, Pappas Konstantinos, Tigas Stelios, Makriyiannis Dimitrios, Antoniou Sophia, Kazakos Nikolaos, Margeli Alexandra, Papassotiriou Ioannis, Tsatsoulis Agathocles, Michalis Lampros K
2nd Department of Cardiology, Medical School, University of Ioannina, Ioannina 45110, Greece; Michaelidion Cardiac Center, Medical School, University of Ioannina, Ioannina 45110, Greece.
Michaelidion Cardiac Center, Medical School, University of Ioannina, Ioannina 45110, Greece; Department of Endocrinology, Medical School, University of Ioannina, Ioannina 45110, Greece.
Clin Biochem. 2018 Mar;53:31-37. doi: 10.1016/j.clinbiochem.2017.12.010. Epub 2017 Dec 27.
The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated.
Patients with T2DM and poor glycemic control without known cardiovascular diseases (n=119) at baseline were enrolled and followed for about 9years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed.
Higher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p<0.05 for all). In univariate Cox regression analysis, PWV>10m/s, YKL-40>78ng/ml and NGAL>42ng/ml were associated with cardiovascular events (p<0.05 for all). In multivariate analysis, after adjusting for classical risk factors and glycemic control, increased NGAL, YKL-40 and PWV and decreased FMD (i.e. ≤2.2%) (p<0.05 for all) were independently associated with cardiovascular events.
In T2DM patients without established cardiovascular disease, novel indices of vascular inflammation (NGAL and YKL-40) were associated with subclinical atherosclerosis (arterial stiffness) but also with adverse clinical prognosis. Arterial stiffness and endothelial dysfunction were also independently related to adverse prognosis.
2型糖尿病（T2DM）中动脉粥样硬化的病理生理学是多因素的。目前研究了血管指标与循环炎症生物标志物和胰岛素抵抗之间的关联及其在T2DM患者长期心血管预后中的作用。
纳入基线时患有T2DM且血糖控制不佳且无已知心血管疾病的患者（n = 119），并随访约9年。终点是任何心血管事件（冠心病、中风、外周动脉疾病或心血管死亡）的发生。评估了主动脉脉搏波速度（PWV）、增强指数（AIx）、肱动脉血流介导的舒张功能（FMD）、高敏C反应蛋白（hsCRP）、几丁质酶3样蛋白1（YKL - 40）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、脂肪酸结合蛋白（FABP - 4）。
较高的YKL - 40和NGAL与较高的PWV相关，而较高的YKL - 40和FABP - 4与较高的AIx相关（所有p<0.05）。在单因素Cox回归分析中，PWV>10m/s、YKL - 40>78ng/ml和NGAL>42ng/ml与心血管事件相关（所有p<0.05）。在多因素分析中，在调整经典危险因素和血糖控制后，NGAL、YKL - 40升高和PWV升高以及FMD降低（即≤2.2%）（所有p<0.05）与心血管事件独立相关。
在无已确诊心血管疾病的T2DM患者中，血管炎症的新指标（NGAL和YKL - 40）与亚临床动脉粥样硬化（动脉僵硬）相关，但也与不良临床预后相关。动脉僵硬和内皮功能障碍也与不良预后独立相关。
