The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial.
The effect of metformin (1000 mg twice a day) on markers of endothelial activation, inflammation, and coagulation was investigated in subjects with impaired glucose tolerance (IGT) in a 16-wk, randomized, placebo-controlled, double-blind study. Soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, C-reactive protein, TNFalpha, von Willebrand factor, and tissue plasminogen activator were measured at baseline and at the end of the trial. Subjects with IGT (n = 55, 14 males and 41 females), aged 48.4 +/- 9.6 yr with a body mass index of 31.4 +/- 5.6 kg/m(2), were studied. All participants followed a 1-month stabilization period in their diet and physical activity. Afterward, 29 subjects were assigned to the treatment group and 26 to the control group. A significant reduction in weight, fasting plasma glucose, soluble intercellular adhesion molecule (306 +/- 75 vs. 268 +/- 61 ng/ml, P = 0.029), soluble vascular cell adhesion molecule (595 +/- 114 vs. 508 +/- 126 ng/ml, P = 0.006), and von Willebrand factor (124 +/- 34 vs. 94 +/- 34%, P = 0.001) was seen in the treatment group, whereas tissue plasminogen activator, TNFalpha, and C-reactive protein levels did not change. No change was seen in the control group. Thus, metformin improves the plasma levels of some markers of endothelial activation and coagulation in subjects with IGT, whereas it has no effect on markers of inflammation.
Clinical Research Center, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
A Enrique
AE
Caballero
Adriano
A
Delgado
Carlos A
CA
Aguilar-Salinas
Alberto Naranjo
AN
Herrera
Jose Luis
JL
Castillo
Tatiana
T
Cabrera
Francisco J
FJ
Gomez-Perez
Juan A
JA
Rull
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000097:blood / Q000737:chemistry; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005215:Fasting / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000097:blood*; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D008954:Models, Biological; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000737:chemistry; D014657:Vasculitis / Q000097:blood*; D015431:Weight Loss; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D007004:Hypoglycemic Agents; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D008687:Metformin