Liu Li, Liang Yuan-Bin, Liu Xiao-Lin, Wang Hong-Qin, Qi Yi-Fei, Wang Min, Chen Bao-Xin, Zhou Qing-Bing, Tong Wen-Xin, Zhang Ying
Graduate School, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Institute of Geriatric Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Heliyon. 2024 Oct 18;10(20):e39554. doi: 10.1016/j.heliyon.2024.e39554. eCollection 2024 Oct 30.
Blood-stasis syndrome (BSS), an important syndrome in Type 2 diabetes mellitus(T2DM), is associated with the pathophysiological mechanisms underlying diabetic vascular complications. However, BSS has not been fully characterized as of yet. Due to the strong correlation between BSS and vasculopathy, we hypothesized that the metabolic characteristics of BSS in T2DM (T2DM BSS) are highly specific. By combining untargeted metabolomics and pseudotargeted lipidomics approaches, this study aimed to comprehensively elucidate the metabolic traits of T2DM BSS, thereby providing novel insights into the vascular complications of diabetes and establishing a foundation for precision medicine.
The survey was conducted in Haidian District of Beijing from October 2021 to November 2021, and data collection was completed in January 2022. Liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS) based pseudotargeted lipidomics were performed to detect metabolites and lipids. Multivariate, univariate, and pathway analyses were utilized to investigate metabolic changes. The unique metabolites of BSS were obtained by inter-group comparisons and screening. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of metabolites.
A total of 1189 participants completed the survey, of which 120 participants were recruited in this study and further divided into a discovery cohort (n = 90) and a validation cohort (n = 30). Among these, 21 participants were selected for psuedotargeted lipidomics analysis. 81 metabolites, mainly involving glycerophospholipids, were identified as unique metabolites of T2DM BSS, while fatty acyls (FAs) were identified as unique lipids. T2DM BSS was associated with significant dysregulation in glycerophospholipid metabolism and choline metabolism within cancer pathways as major metabolic disturbances. Furthermore, analyses of both the discovery and validation cohorts, indicated that LysoPC (20:5(5Z,8Z,11Z,14Z,17Z)/0:0) and LysoPC (15:0) had the greatest impact on distinguishing BSS.
Altered levels of glycerophospholipids and FAs have been associated with T2DM BSS. These results provide valuable mechanistic insights linked with the development of BSS in T2DM subjects.
血瘀证（BSS）是2型糖尿病（T2DM）的一种重要证型，与糖尿病血管并发症的病理生理机制相关。然而，BSS尚未得到充分的表征。由于BSS与血管病变之间存在很强的相关性，我们推测T2DM中BSS的代谢特征具有高度特异性。本研究通过结合非靶向代谢组学和伪靶向脂质组学方法，旨在全面阐明T2DM BSS的代谢特征，从而为糖尿病血管并发症提供新的见解，并为精准医学奠定基础。
于2021年10月至2021年11月在北京海淀区进行调查，并于2022年1月完成数据收集。采用基于液相色谱-质谱（LC-MS）的非靶向代谢组学和基于液相色谱-串联质谱（LC-MS/MS）的伪靶向脂质组学来检测代谢物和脂质。利用多变量、单变量和通路分析来研究代谢变化。通过组间比较和筛选获得BSS的独特代谢物。进行受试者工作特征（ROC）曲线分析以评估代谢物的诊断准确性。
共有1189名参与者完成了调查，其中120名参与者被纳入本研究，并进一步分为发现队列（n = 90）和验证队列（n = 30）。其中，21名参与者被选用于伪靶向脂质组学分析。81种代谢物，主要涉及甘油磷脂，被鉴定为T2DM BSS的独特代谢物，而脂肪酰（FAs）被鉴定为独特脂质。T2DM BSS与癌症通路中的甘油磷脂代谢和胆碱代谢的显著失调相关，这是主要的代谢紊乱。此外，对发现队列和验证队列的分析均表明，溶血磷脂酰胆碱（20:5(5Z,8Z,11Z,14Z,17Z)/0:0）和溶血磷脂酰胆碱（15:）对区分BSS的影响最大。
甘油磷脂和FAs水平的改变与T2DM BSS相关。这些结果为T2DM患者中BSS的发展提供了有价值的机制见解。
