Effect of PPAR-gamma agonist treatment on markers of endothelial dysfunction in patients with type 2 diabetes mellitus.
Thiazolidinediones are insulin-sensitizing drugs acting through peroxisome proliferator-activated receptor (PPAR)-gamma. The aim of our study was to evaluate the effect of 5-month treatment with PPAR-gamma agonist--rosiglitazone (4 mg/day), on the circulating markers of endothelial dysfunction and to evaluate the role of changes in endocrine function of adipose tissue in this process. Biochemical and metabolic parameters, circulating adiponectin, resistin, ICAM-1, VCAM-1, E-selectin, P-selectin, PAI-1, myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) concentrations were assessed in 10 women with type 2 DM before and after rosiglitazone treatment and in a control group of healthy women. At baseline, diabetic group had significantly higher serum concentrations of glucose, glycated hemoglobin, V-CAM and PAI-1 compared to control group. Adiponectin levels tended to be lower in diabetic group, while resistin concentrations did not differ from control group. Rosiglitazone treatment improved diabetes compensation, significantly reduced VCAM-1, PAI-1 and E-selectin concentrations and increased adiponectin levels, while it did not affect serum resistin concentrations. Adiponectin concentrations at baseline were inversely related to E-selectin and MPO levels, this correlation disappeared after rosiglitazone treatment. We conclude that 5-month rosiglitazone treatment significantly reduced several markers of endothelial dysfunction. This effect could be at least in part attributable to marked increase of circulating adiponectin levels.
Doležalová
R
R
Third Department of Internal Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Haluzík
M M
MM
Bošanská
L
L
Lacinová
Z
Z
Kasalová
Z
Z
Stulc
T
T
Haluzík
M
M
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood* / Q000473:pathology / Q000517:prevention & control*; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D009195:Peroxidase / Q000097:blood; D052243:Resistin / Q000097:blood; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D019040:E-Selectin; D007004:Hypoglycemic Agents; D008055:Lipids; D047495:PPAR gamma; D052243:Resistin; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9