Skip to main content
Top
Published in: Diabetologia 12/2009

01-12-2009 | Short Communication

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

Authors: V. D. F. de Mello, M. Lankinen, U. Schwab, M. Kolehmainen, S. Lehto, T. Seppänen-Laakso, M. Orešič, L. Pulkkinen, M. Uusitupa, A. T. Erkkilä

Published in: Diabetologia | Issue 12/2009

Login to get access

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-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.
Literature
1.
2.
go back to reference van Gaal LF, Mertens IL, de Block CE (2006) Mechanisms linking obesity with cardiovascular disease. Nature 444:875–880CrossRefPubMed van Gaal LF, Mertens IL, de Block CE (2006) Mechanisms linking obesity with cardiovascular disease. Nature 444:875–880CrossRefPubMed
3.
go back to reference Laaksonen DE, Niskanen L, Nyyssonen K et al (2004) C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 47:1403–1410CrossRefPubMed Laaksonen DE, Niskanen L, Nyyssonen K et al (2004) C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 47:1403–1410CrossRefPubMed
4.
go back to reference Pradhan AD, Ridker PM (2002) Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur Heart J 23:831–834CrossRefPubMed Pradhan AD, Ridker PM (2002) Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur Heart J 23:831–834CrossRefPubMed
5.
go back to reference Holland WL, Knotts TA, Chavez JA, Wang LP, Hoehn KL, Summers SA (2007) Lipid mediators of insulin resistance. Nutr Rev 65:S39–S46CrossRefPubMed Holland WL, Knotts TA, Chavez JA, Wang LP, Hoehn KL, Summers SA (2007) Lipid mediators of insulin resistance. Nutr Rev 65:S39–S46CrossRefPubMed
6.
go back to reference Bressler P, Bailey SR, Matsuda M, DeFronzo RA (1996) Insulin resistance and coronary artery disease. Diabetologia 39:1345–1350CrossRefPubMed Bressler P, Bailey SR, Matsuda M, DeFronzo RA (1996) Insulin resistance and coronary artery disease. Diabetologia 39:1345–1350CrossRefPubMed
7.
go back to reference Erkkilä AT, Schwab US, de Mello VD et al (2008) Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications. Eur J Nutr 47:319–328CrossRefPubMed Erkkilä AT, Schwab US, de Mello VD et al (2008) Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications. Eur J Nutr 47:319–328CrossRefPubMed
8.
go back to reference Lankinen M, Schwab US, Erkkilä AT et al (2009) Fatty fish intake decreases lipids related to inflammation and insulin signaling—a lipidomics approach. PLoS ONE 4:e5258CrossRefPubMed Lankinen M, Schwab US, Erkkilä AT et al (2009) Fatty fish intake decreases lipids related to inflammation and insulin signaling—a lipidomics approach. PLoS ONE 4:e5258CrossRefPubMed
9.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed
10.
go back to reference Haus JM, Kashyap SR, Kasumov T et al (2009) Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58:337–343CrossRefPubMed Haus JM, Kashyap SR, Kasumov T et al (2009) Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58:337–343CrossRefPubMed
11.
go back to reference Wu D, Marko M, Claycombe K, Paulson KE, Meydani SN (2003) Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-κ B activity. J Biol Chem 278:10983–10992CrossRefPubMed Wu D, Marko M, Claycombe K, Paulson KE, Meydani SN (2003) Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-κ B activity. J Biol Chem 278:10983–10992CrossRefPubMed
12.
go back to reference Vanden Berghe W, Vermeulen L, de Wilde G, de Bosscher K, Boone E, Haegeman G (2000) Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol 60:1185–1195CrossRefPubMed Vanden Berghe W, Vermeulen L, de Wilde G, de Bosscher K, Boone E, Haegeman G (2000) Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol 60:1185–1195CrossRefPubMed
13.
go back to reference Yuan M, Konstantopoulos N, Lee J et al (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293:1673–1677CrossRefPubMed Yuan M, Konstantopoulos N, Lee J et al (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293:1673–1677CrossRefPubMed
14.
go back to reference Devaraj S, Venugopal SK, Singh U, Jialal I (2005) Hyperglycemia induces monocytic release of interleukin-6 via induction of protein kinase C-α and -β. Diabetes 54:85–91CrossRefPubMed Devaraj S, Venugopal SK, Singh U, Jialal I (2005) Hyperglycemia induces monocytic release of interleukin-6 via induction of protein kinase C-α and -β. Diabetes 54:85–91CrossRefPubMed
Metadata
Title
Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease
Authors
V. D. F. de Mello
M. Lankinen
U. Schwab
M. Kolehmainen
S. Lehto
T. Seppänen-Laakso
M. Orešič
L. Pulkkinen
M. Uusitupa
A. T. Erkkilä
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 12/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1482-9

Other articles of this Issue 12/2009

Diabetologia 12/2009 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.