Abstract
Objective
This study was designed to investigate whether metformin affects monocyte secretory
function in patients with impaired fasting glucose receiving chronic statin therapy.
Materials/Methods
The study included 48 patients with impaired fasting glucose treated for at least
three months with simvastatin (40 mg daily). These patients were randomized to either metformin (3 g daily) or placebo, which was administered together with simvastatin for 90 days. Plasma lipids, glucose homeostasis markers, monocyte cytokine release and plasma
C-reactive protein levels were determined before randomization and at the end of the
treatment.
Results
Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-α,
interleukin-1β, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8,
as well as decreased plasma C-reactive protein levels, which were accompanied by an
improvement in insulin sensitivity.
Conclusions
The obtained results suggest that metformin may inhibit monocyte secretory function
and reduce systemic inflammation in statin-treated patients with prediabetes. Impaired
fasting glucose patients with high cardiovascular risk may receive the greatest benefits
from concomitant treatment with a statin and metformin.
Keywords
Abbreviations:
CRP (C-reactive protein), FFA (free fatty acids), HbA1c (glycated hemoglobin), HDL (high-density lipoprotein), HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), hsCRP (high sensitivity C-reactive protein), IFG (impaired fasting glucose), LDL (low-density lipoprotein), MCP-1 (monocyte chemoattractant protein-1), TNF-α (tumor necrosis factor-α)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Metabolism - Clinical and ExperimentalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study Group.Lancet. 1994; 344: 1383-1389
- Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group..N Engl J Med. 1995; 333: 1301-1307
- Pleiotropic effects of statins—clinical evidence.Curr Pharm Des. 2009; 15: 479-489
- The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis.Atherosclerosis. 2009; 203: 325-330
- Rosuvastatin to prevent vascular events in men and women with elevated C- reactive protein.N Engl J Med. 2008; 359: 2195-2207
- CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.Lancet. 2004; 364: 685-696
- Inflammatory mechanisms in atherosclerosis.J Thromb Haemost. 2009; 7: 328-331
- Macrophages: promising targets for the treatment of atherosclerosis.Curr Vasc Pharmacol. 2009; 7: 234-243
Krysiak R, Gdula-Dymek A, Okopien B. Effect of simvastatin and fenofibrate on cytokine release and systemic inflammation in type 2 diabetes mellitus with mixed dyslipidemia. Am J Cardiol 2011;107:1010–8.e1.
- Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia.Diabetes Care. 2009; 32: 1421-1424
- Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates.J Cardiovasc Pharmacol. 2005; 46: 377-386
- Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance.J Clin Endocrinol Metab. 2006; 91: 1770-1778
- Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of pre-diabetes.Diabetes Care. 2010; 33: 2266-2270
- Chemokines and cardiovascular risk.Arterioscler Thromb Vasc Biol. 2008; 28: 1909-1919
- Impaired glucose tolerance and impaired fasting glucose—a review of diagnosis, clinical implications and management.Diab Vasc Dis Res. 2005; 2: 9-15
- Pathobiology of atherosclerosis—a brief review.Semin Thromb Hemost. 2004; 30: 665-672
- Cytokines in atherosclerosis: pathogenic and regulatory pathways.Physiol Rev. 2006; 86: 515-581
- Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403
- Effects of simvastatin and metformin on inflammation and insulin resistance in individuals with mild metabolic syndrome.Am J Cardiovasc Drugs. 2007; 7: 219-224
- Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?.Braz J Med Biol Res. 2007; 40: 229-235
Article info
Publication history
Published online: July 30, 2012
Accepted:
June 26,
2012
Received:
March 24,
2012
Footnotes
Institutional approval: The study was approved by the Bioethical Committee of the Medical University of Silesia.
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
