title: 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.
  
  
  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; 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(2α) correlated positively with lipoprotein-associated phospholipase A(2), 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.
authors.affiliation: Interdisciplinary Course of Science for Aging, Graduate School, Yonsei University, Seoul, Korea.
authors.forename: Chang Young
authors.initials: CY
authors.lastname: Ha
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jean Kyung
authors.initials: JK
authors.lastname: Paik
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
authors.forename: Yong-Han
authors.initials: YH
authors.lastname: Paik
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress; D010743:Phospholipids / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D015850:Interleukin-6; D008054:Lipid Peroxides; D008055:Lipids; D008077:Lipoproteins, LDL; D010743:Phospholipids; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein