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; 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: Chang Young Ha, Ji Young Kim, Jean Kyung Paik, Oh Yoen Kim, Yong-Han Paik, Eun Jig Lee, Jong Ho Lee
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 76 Issue 5 Pg. 674-82 (May 2012) ISSN: 1365-2265 [Electronic] England
• PMID: 21958081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

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

Topics

• Adult
• Aged
• Biomarkers (blood)
• Blood Glucose (metabolism)
• C-Reactive Protein (metabolism)
• Chromatography, High Pressure Liquid (methods)
• Diabetes Mellitus, Type 2 (blood, metabolism)
• Humans
• Inflammation (blood, metabolism)
• Interleukin-6 (blood)
• Lipid Metabolism
• Lipid Peroxides (blood)
• Lipids (blood, 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