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Association of circulating metabolic intermediates with inflammatory and oxidative stress markers and arterial stiffness in male patients with newly-diagnosed type 2 diabetes
( Chang Young Ha ) , ( Ji Young Kim ) , ( Jean Kyung Paik ) , ( Oh Yoen Kim ) , ( Eun Jig Lee ) , ( Jong Ho Lee )
UCI I410-ECN-0102-2021-500-000136331
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Objective To determine whether circulating metabolic intermediates are associated with inflammation, oxidative stress, and arterial stiffness in men with newly-diagnosed type 2 diabetes. Methods Men with newly-diagnosed type 2 diabetes (n=26) and age- and body mass index-matched healthy men (n=27) were included. We measured levels of inflammatory and oxidative markers, and arterial stiffness by brachial-ankle pulse wave velocity (ba-PWV). Metabolomic profiling was analyzed with ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry. Results Diabetes patients showed higher circulating levels of glucose, triglyceride, oxidized- LDL, high sensitivity C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), homeostasis model assessment-insulin resistance, urinary 8-epi-prostaglandin F2α (8-epi-PGF2α), and ba-PWV than healthy men. In plasma, 19 metabolites including 3 amino acids (leucine, lysine, and phenylalanine), 8 acylcarnitines (propionyl-, octanoyl-, decanoyl-, palmityl-, heptadecanoyl-, linoleyl-, and vaccenyl-carnitines), 6 lyso-phosphatidylcholines (lysoPCs) (C14:0, C16:1, C18:1, C18:3, C20:5, and C22:6), and 2 lyso-phosphatidylethanolamines (lysoPEs) (C18:2 and C22:6) significantly increased in diabetes patients, whereas serine and lysoPE (C18:1) decreased. Decanoyl carnitine, lysoPCs (C14:0, C16:1, C18:1, and C22:6), and lysoPE (C18:1) with variable importance in the projection values >1.0 were major plasma metabolites that distinguished healthy and diabetic men. Decanoyl carnitine positively correlated with oxidized-LDL, 8-epi-PGF2α, IL-6, and TNF-α, and ba-PWV. Ba-PWV correlated positively with lysoPCs C14:0 and C16:1, and negatively with lysoPE C18:1. 8-epi-PGF2α correlated positively with lipoprotein-associated phospholipase A2, ba-PWV and lysoPCs (C14:0 and C16:1). Conclusion Metabolic analysis revealed that circulating intermediate metabolites can be closely associated with inflammation, oxidative stress, and arterial stiffness in early diabetes.

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