Yang Hsin-Yu, Wu Du-An, Chen Ming-Chun, Hsu Bang-Gee
1 School of Medicine, Tzu Chi University, Hualien, Taiwan.
2 Division of Metabolism and Endocrinology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Diab Vasc Dis Res. 2019 May;16(3):281-288. doi: 10.1177/1479164118816661. Epub 2018 Dec 14.
Sclerostin and Dickkopf-1 are extracellular inhibitors of the canonical Wnt/β-catenin signalling pathway, which is implicated in the development of arterial stiffness. However, the correlation between aortic stiffness and sclerostin or Dickkopf-1 levels in patients with type 2 diabetes mellitus is unknown.
Fasting blood samples were collected from 125 patients with type 2 diabetes mellitus. Aortic stiffness was measured by carotid-femoral pulse wave velocity, and high aortic stiffness was defined by a carotid-femoral pulse wave velocity of >10 m/s. The serum sclerostin and Dickkopf-1 concentrations were determined using commercially available enzyme-linked immunosorbent assays.
In total, 46 patients with type 2 diabetes mellitus (36.8%) had high levels of aortic stiffness. Compared to the control group without aortic stiffness, this group was significantly older, had higher systolic and diastolic blood pressures, had higher blood urea nitrogen, creatinine, urinary albumin-to-creatinine ratio and serum sclerostin levels, and had significantly lower high-density lipoprotein cholesterol levels and estimated glomerular filtration rates. After adjusting for confounders, serum sclerostin [odds ratio = 1.005 (1.002-1.007), p = 0.002] levels remained an independent predictor of aortic stiffness. Multivariate analysis showed that the serum sclerostin level ( β = 0.374, adjusted R change = 0.221, p < 0.001) was positively associated with carotid-femoral pulse wave velocity.
Serum levels of sclerostin, but not Dickkopf-1, are positively correlated with carotid-femoral pulse wave velocity and independently predict aortic stiffness in patients with type 2 diabetes mellitus.
硬化素和Dickkopf-1是经典Wnt/β-连环蛋白信号通路的细胞外抑制剂，该信号通路与动脉僵硬度的发展有关。然而，2型糖尿病患者主动脉僵硬度与硬化素或Dickkopf-1水平之间的相关性尚不清楚。
收集125例2型糖尿病患者的空腹血样。通过颈股脉搏波速度测量主动脉僵硬度，颈股脉搏波速度>10m/s定义为高主动脉僵硬度。使用市售酶联免疫吸附测定法测定血清硬化素和Dickkopf-1浓度。
共有46例2型糖尿病患者（36.8%）主动脉僵硬度较高。与无主动脉僵硬度的对照组相比，该组患者年龄显著更大，收缩压和舒张压更高，血尿素氮、肌酐、尿白蛋白与肌酐比值及血清硬化素水平更高，高密度脂蛋白胆固醇水平和估计肾小球滤过率显著更低。在调整混杂因素后，血清硬化素[比值比=1.005（1.002-1.007），p=0.002]水平仍是主动脉僵硬度的独立预测因子。多变量分析显示，血清硬化素水平（β=0.374，调整后R变化=0.221，p<0.001）与颈股脉搏波速度呈正相关。
血清硬化素水平而非Dickkopf-1水平与颈股脉搏波速度呈正相关，并独立预测2型糖尿病患者的主动脉僵硬度。
