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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

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Summary

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 (8‐epi‐PGF) 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 >1ยท0 were major plasma metabolites that distinguished nondiabetic and diabetic men. Decanoyl carnitine positively correlated with oxidized LDL, 8‐epi‐PGF, 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 correlated 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.
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Document Type: Research Article

Affiliations: 1: Interdisciplinary Course of Science for Aging, Graduate School, Yonsei University 2: Department of Internal Medicine, Samsung Medical Center

Publication date: May 1, 2012

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