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

Clin Endocrinol (Oxf). 2012 May;76(5):674-82. doi: 10.1111/j.1365-2265.2011.04244.x.

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; 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • C-Reactive Protein / metabolism
  • Chromatography, High Pressure Liquid / methods
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism*
  • Interleukin-6 / blood
  • Lipid Metabolism*
  • Lipid Peroxides / blood
  • Lipids / blood
  • Lipids / chemistry
  • Lipoproteins, LDL / blood
  • Male
  • Mass Spectrometry / methods
  • Metabolome
  • Metabolomics / methods
  • Middle Aged
  • Multivariate Analysis
  • Oxidative Stress*
  • Phospholipids / blood
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Stiffness*

Substances

  • Biomarkers
  • Blood Glucose
  • Interleukin-6
  • Lipid Peroxides
  • Lipids
  • Lipoproteins, LDL
  • Phospholipids
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • oxidized low density lipoprotein
  • C-Reactive Protein