Low Serena, Pek Sharon, Moh Angela, Liu Jian-Jun, Pandian Bhuvaneswari, Ang Keven, Tang Wern Ee, Lim Ziliang, Subramaniam Tavintharan, Sum Chee Fang, Lim Su Chi
Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore.
Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore.
Diab Vasc Dis Res. 2024 Nov-Dec;21(6):14791641241304435. doi: 10.1177/14791641241304435.
: Osteoprotegerin (OPG) inhibits vascular calcification which is central to pathogenesis of arterial stiffness. However, it promotes inflammation by upregulating expression of vascular cell adhesion molecule-1(VCAM-1), thereby contributing to arterial stiffness. We investigated longitudinal association between OPG and arterial stiffness in type 2 diabetes (T2D), causality of the association and mediation by VCAM-1. : This was a prospective cohort study of T2D patients ( = 1877, mean age 57.0 ± 10.8) with 10 years' follow-up. Baseline plasma OPG was measured using immunoassay. Pulse wave velocity (PWV) was assessed using applanation tonometry. We examined association between OPG and follow-up PWV using linear mixed model. One-sample Mendelian Randomization (MR) was conducted with rs1385492 as OPG-associated single nucleotide polymorphism (SNP). : Baseline natural log (Ln)-transformed OPG was positively associated with baseline and follow-up PWV with adjusted coefficients 0.43 (95%CI 0.05, 0.80; = .026) and 0.51 (95%CI 0.06 to 0.97; = .028) respectively. Genetically-predicted higher levels of plasma OPG was associated with higher last follow-up PWV with coefficient 10.81 (95%CI 2.97, 18.65; = .007) per unit increase in LnOPG. Higher VCAM-1 accounted for 10.2% of association between LnOPG and follow-up PWV. : Baseline plasma OPG was associated with higher follow-up PWV in patients with T2D, with genetic evidence from MR. This association may be mediated, at least in part, by VCAM-1.
骨保护素（OPG）可抑制血管钙化，而血管钙化是动脉僵硬度发病机制的核心。然而，它通过上调血管细胞黏附分子-1（VCAM-1）的表达促进炎症，从而导致动脉僵硬度增加。我们研究了2型糖尿病（T2D）患者中OPG与动脉僵硬度之间的纵向关联、该关联的因果关系以及VCAM-1的介导作用。
这是一项对1877例T2D患者（平均年龄57.0±10.8岁）进行的前瞻性队列研究，随访10年。采用免疫测定法测量基线血浆OPG。使用压平式眼压计评估脉搏波速度（PWV）。我们使用线性混合模型检查OPG与随访PWV之间的关联。以rs1385492作为与OPG相关的单核苷酸多态性（SNP）进行单样本孟德尔随机化（MR）分析。
基线自然对数（Ln）转换后的OPG与基线和随访PWV呈正相关，调整系数分别为0.43（95%CI 0.05，0.80；P = 0.026）和0.51（95%CI 0.06至0.97；P = 0.028）。基因预测的血浆OPG水平升高与末次随访时较高的PWV相关，每单位LnOPG增加，系数为10.81（95%CI 2.97，18.65；P = 0.007）。较高的VCAM-1占LnOPG与随访PWV之间关联的10.2%。
T2D患者的基线血浆OPG与较高的随访PWV相关，且有MR的基因证据。这种关联可能至少部分由VCAM-1介导。
