School of Medicine, Tzu Chi University, Hualien, Taiwan.
Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Medicine (Baltimore). 2023 Sep 8;102(36):e34649. doi: 10.1097/MD.0000000000034649.
Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/β-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0-1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (β = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (β = -0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (β = -0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (β = -0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.
骨硬化蛋白和 Dickkopf-1(DKK1)是经典 Wnt/β-连环蛋白信号通路的细胞外抑制剂,与血管衰老和动脉粥样硬化有关。本研究旨在评估 2 型糖尿病(T2DM)患者的骨硬化蛋白和 DKK1 浓度与血管反应性指数(VRI)测量的内皮功能之间的相关性。从 100 名 T2DM 患者中采集空腹血样。使用数字热监测测量内皮功能和 VRI,并通过酶联免疫吸附试验测量循环骨硬化蛋白和 DKK1 水平。VRI 值<1.0、1.0-1.9 和>2.0 分别表示血管反应性差、中等和良好。总体而言,分别有 30、38 和 32 名患者的血管反应性差、中等和良好。年龄较大、血清糖化血红蛋白、尿白蛋白与肌酐比值较高以及骨硬化蛋白水平较低,高血压患病率、收缩压和舒张压(DBP)较低与较差的 VRI 相关。多变量逐步线性回归分析显示 DBP(β=0.294,调整后的 R2 变化=0.098,P<0.001)、糖化血红蛋白对数(β=-0.235,调整后的 R2 变化=0.050,P=0.002)、尿白蛋白与肌酐比值对数(β=-0.342,调整后的 R2 变化=0.227,P<0.001)和骨硬化蛋白水平对数(β=-0.327,调整后的 R2 变化=0.101,P<0.001)与 VRI 独立相关。血清骨硬化蛋白与糖化血红蛋白和白蛋白与肌酐比值一起与 VRI 呈负相关,而 DBP 与 VRI 呈正相关。这些因素可独立预测 T2DM 患者的内皮功能障碍。