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.

ABSTRACT

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 time-of-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 factor-alpha (TNF-α), 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; C182 and C226) significantly increased in diabetes men, whereas serine and lysoPE (C181) decreased. Decanoyl carnitine, lysoPCs (C140, C161, C181 and C226) and lysoPE (C181) 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 C140 and C161, and negatively with lysoPE C181. 8-epi-PGF(2α) correlated positively with lipoprotein-associated phospholipase A(2), ba-PWV and lysoPCs (C140 and C161). The receiver operating characteristic curve estimation suggested that decanoyl carnitine and lysoPC (C140) 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.