The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes

Objective: To determine whether circulating metabolic intermediates are associated with inflammation, oxidative stress and arterial stiffness in men with newly diagnosed type 2 diabetes and investigate the circulating metabolic intermediates that may predict the risk of developing diabetes. Research design and methods: Men with newly diagnosed type 2 diabetes (n = 26) and age- and body mass index-matched nondiabetic 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 analysed with ultra performance liquid chromatography and quadrupole timeof- flight mass spectrometry. Results: Diabetic men showed higher circulating levels of glucose, triglyceride, oxidized low-density lipoprotein (LDL), high-sensitivity C-reactive protein, interleukin (IL)-6, tumour necrosis factoralpha (TNF-a), homeostasis model assessment-insulin resistance, urinary 8-epi-prostaglandin F _2α (8-epi-PGF _2α) and ba-PWV than nondiabetic men. In plasma, 19 metabolites including three amino acids, eight acylcarnitines, six lysophosphatidylcholines (lysoPCs), and two lysophosphatidylethanolamines (lysoPEs; C18:2 and C22:6) significantly increased in diabetes men, 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 nondiabetic and diabetic men. Decanoyl carnitine positively correlated with oxidized LDL, 8-epi-PGF _2α, IL-6, TNF-α and ba-PWV. ba-PWV correlated positively with lysoPCs C14:0 and C16:1, and negatively with lysoPE C18:1. 8-epi-PGF _2αcorrelated positively with lipoprotein-associated phospholipase A2, ba-PWV and lysoPCs (C14:0 and C16:1). The receiver operating characteristic curve estimation suggested that decanoyl carnitine and lysoPC (C14:0) are the best metabolites for predicting the risk of developing diabetes. Conclusions: Circulating lipid-related intermediate metabolites can be closely associated with inflammation, oxidative stress and arterial stiffness in early diabetes.