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Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus

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Abstract

Objective

Metformin may influence atherogenesis but the mechanisms are not well understood. A pilot study was undertaken to determine whether metformin administration is associated with changes in oxidative stress and endothelial function.

Methods

Fifteen type 2 diabetic patients were treated for 3 months with metformin (1,700 mg daily) or with a placebo in a crossover study. Laboratory parameters of oxidative stress, fibrinolysis and endothelial function were evaluated both prior to and following the respective treatments. In addition, laser Doppler was used to determine microcirculation changes in the skin.

Results

Increases in serum N-acetyl-β-glucosaminidase activity (p < 0.05) and plasma malondialdehyde concentration were found following 1 month of metformin administration. Three months of treatment was accompanied by significantly increased plasma malondialdehyde (p < 0.001) and ascorbic acid (p < 0.01) concentrations as well as the alpha-tocopherol/(cholesterol + triglyceride) ratio (p < 0.001). The concentration of tissue plasminogen activator (tPA), vascular cell-adhesion molecules (VCAM) and intercellular cell-adhesion molecules (ICAM) were significantly decreased (p < 0.01) compared with placebo. Microcirculation measured by laser Doppler flowmetry was not significantly changed.

Conclusions

We conclude that initiation of metformin treatment in type 2 diabetic patients is associated with improved diabetes control as well as with activation of oxidative stress together with antioxidant system. The atherogenic process measured by biochemical indicators is diminished in parallel. Our results show that in short-term metformin administration in type 2 diabetes promotes endothelium effects associated with a complex of metabolic changes.

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Acknowledgement

The authors are indebted to Marcela Jarolímková, Hana Homolková and Jana Mrázková for technical assistance. We thank Dr. Nicolas Wierensperger for valuable discussion. The study was supported by the Research Project MSM0021620807 of the Ministery of Education and by Merck Santé.

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Authors and Affiliations

  1. Laboratory for Endocrinology and Metabolism, 3rd Department of Internal Medicine, First Faculty of Medicine, Charles University, U Nemocnice 1, 128 08, Prague 2, Czech Republic

    Jan Škrha, Martin Prázný & Jiřina Hilgertová

  2. Department of Clinical Hematology, First Faculty of Medicine, Charles University, Prague, Czech Republic

    Jan Kvasnička

  3. Department of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic

    Marta Kalousová & Tomáš Zima

Authors
  1. Jan Škrha
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  2. Martin Prázný
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  3. Jiřina Hilgertová
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  4. Jan Kvasnička
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  5. Marta Kalousová
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  6. Tomáš Zima
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Correspondence to Jan Škrha.

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Škrha, J., Prázný, M., Hilgertová, J. et al. Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus. Eur J Clin Pharmacol 63, 1107–1114 (2007). https://doi.org/10.1007/s00228-007-0378-1

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  • DOI: https://doi.org/10.1007/s00228-007-0378-1

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