Plasma metabolic profiling in male patients with newly-diagnosed type 2 diabetes : association with inflammatory and oxidative stress markers and arterial stiffness

Abstract

This study investigated whether circulating metabolic intermediates are associated with inflammation, oxidative stress, and arterial stiffness in newly-diagnosed type 2 diabetes men. newly-diagnosed type 2 diabetes men (n=26) and age- and body mass index-matched healthy men (n=27) were included. We measured inflammatory and oxidative markers and arterial stiffness by brachial-ankle pulse wave velocity (ba-PWV). Metabolomic profiling was analyzed with UPLC/Q-TOF MS. Diabetes patients showed higher levels of glucose, triglyceride, oxidized-LDL, hs 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 leucine, lysine and phenylalanine , 8 acylcarnitines, 6 lyso-phosphatidylcholines (lysoPCs) and 2 lyso-phosphatidylethanolamines (lysoPEs) 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) 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 phospholipaseA2, ba-PWV and lysoPCs (C14:0 and C16:1). Metabolic analysis revealed that circulating intermediate metabolites are closely associated with inflammation, oxidative stress, and arterial stiffness in early diabetes.