Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus.
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-beta-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.
Skrha
Jan
J
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.skrha@lf1.cuni.cz
Prázný
Martin
M
Hilgertová
Jirina
J
Kvasnicka
Jan
J
Kalousová
Marta
M
Zima
Tomás
T
D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D012867:Skin / Q000098:blood supply / Q000187:drug effects
D007004:Hypoglycemic Agents; D008315:Malondialdehyde; D008687:Metformin