Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, Osaka, Japan.
Cardiovasc Diabetol. 2020 Jun 11;19(1):75. doi: 10.1186/s12933-020-01057-w.
Although an increased arterial stiffness has been associated with traditional coronary risk factors, the risk factors and pathology of arterial stiffness remain unclear. In this study, we aimed to identify the plasma metabolites associated with arterial stiffness in patients with type 2 diabetes mellitus.
We used the metabolomic data of 209 patients with type 2 diabetes as the first dataset for screening. To form the second dataset for validation, we enlisted an additional 31 individuals with type 2 diabetes. The non-targeted metabolome analysis of fasting plasma samples using gas chromatography coupled with mass spectrometry and the measurement of brachial-ankle pulse wave velocity (baPWV) were performed.
A total of 65 annotated metabolites were detected. In the screening dataset, there were statistically significant associations between the baPWV and plasma levels of indoxyl sulfate (r = 0.226, p = 0.001), mannitol (r = 0.178, p = 0.010), mesoerythritol (r = 0.234, p = 0.001), and pyroglutamic acid (r = 0.182, p = 0.008). Multivariate regression analyses revealed that the plasma levels of mesoerythritol were significantly (β = 0.163, p = 0.025) and that of indoxyl sulfate were marginally (β = 0.124, p = 0.076) associated with baPWV, even after adjusting for traditional coronary risk factors. In the independent validation dataset, there was a statistically significant association between the baPWV and plasma levels of indoxyl sulfate (r = 0.430, p = 0.016). However, significant associations between the baPWV and plasma levels of the other three metabolites were not confirmed.
CONCLUSIONS/INTERPRETATION: The plasma levels of indoxyl sulfate were associated with arterial stiffness in Japanese patients with type 2 diabetes. Although the plasma levels of mannitol, mesoerythritol, and pyroglutamic acid were also associated with arterial stiffness, further investigation is needed to verify the results.
尽管动脉僵硬度的增加与传统的冠状动脉危险因素有关，但动脉僵硬度的危险因素和病理学仍不清楚。在这项研究中，我们旨在确定 2 型糖尿病患者与动脉僵硬度相关的血浆代谢物。
我们使用 209 例 2 型糖尿病患者的代谢组学数据作为筛选的第一组数据。为了形成验证的第二组数据集，我们又招募了 31 名 2 型糖尿病患者。使用气相色谱-质谱联用技术对空腹血浆样本进行非靶向代谢组分析，并测量肱踝脉搏波速度（baPWV）。
共检测到 65 种注释代谢物。在筛选数据集，baPWV 与血浆中吲哚硫酸（r=0.226，p=0.001）、甘露醇（r=0.178，p=0.010）、赤藓糖醇（r=0.234，p=0.001）和吡咯烷酮羧酸（r=0.182，p=0.008）的水平呈统计学显著相关。多元回归分析显示，赤藓糖醇的血浆水平与 baPWV 显著相关（β=0.163，p=0.025），吲哚硫酸的血浆水平也有边际相关性（β=0.124，p=0.076），即使在调整了传统的冠状动脉危险因素后也是如此。在独立的验证数据集，baPWV 与血浆中吲哚硫酸的水平呈统计学显著相关（r=0.430，p=0.016）。然而，baPWV 与其他三种代谢物的血浆水平之间的显著相关性并未得到证实。
结论/解释：在日本 2 型糖尿病患者中，血浆中吲哚硫酸的水平与动脉僵硬度相关。虽然甘露醇、赤藓糖醇和吡咯烷酮羧酸的血浆水平也与动脉僵硬度相关，但需要进一步的研究来验证这些结果。
