Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease

Diabetologia. 2009 Dec;52(12):2612-5. doi: 10.1007/s00125-009-1482-9. Epub 2009 Aug 11.

Abstract

Aims/hypothesis: Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-alpha and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD.

Methods: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index).

Results: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-alpha or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-alpha or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001).

Conclusions/interpretation: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.

Trial registration: ClinicalTrials.gov NCT00720655.

MeSH terms

  • C-Reactive Protein / metabolism
  • Ceramides / blood*
  • Coronary Disease / blood*
  • Coronary Disease / physiopathology
  • Cross-Sectional Studies
  • Humans
  • Inflammation / blood*
  • Interleukin-6 / blood*
  • Ischemia / blood
  • Ischemia / physiopathology
  • Lipids / blood
  • Myocardial Infarction / blood
  • Myocardial Infarction / physiopathology
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Ceramides
  • Interleukin-6
  • Lipids
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00720655