[HTML][HTML] Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease
VDF De Mello, M Lankinen, U Schwab, M Kolehmainen… - Diabetologia, 2009 - Springer
VDF De Mello, M Lankinen, U Schwab, M Kolehmainen, S Lehto, T Seppänen-Laakso…
Diabetologia, 2009•SpringerAims/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-α 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 …
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-α 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 …
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-α 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-α 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-α 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-α 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
Funding
The study was supported by the Finnish Cultural Foundation, the North-Savo Regional Fund of the Finnish Cultural Foundation, the Yrjö Jahnsson Foundation, the Sigrid Juselius Foundation, the Juho Vainio Foundation, the Kuopio University Hospital (grant 510RA07), the Academy of Finland (Projects 117844 and 118590) and by the Nordic Centre of Excellence on ‘Systems biology in controlled dietary interventions and cohort studies’ (SYSDIET), Project 070014.
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