Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment.
Adhesion molecules, particularly intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin, have been associated with cardiovascular disease. Elevated levels of these molecules have been reported in diabetic patients. Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease, and evidence suggests that postprandial hypertriglyceridemia and hyperglycemia may induce an increase in circulating adhesion molecules. However, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate three different meals: a high-fat meal, 75 g of glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, plasma nitrotyrosine, ICAM-1, VCAM-1, and E-selectin were assayed during the tests. Subsequently, diabetic subjects took simvastatin 40 mg/day or placebo for 12 weeks. The three tests were performed again at baseline, between 3 and 6 days after starting the study, and at the end of each study. High-fat load and glucose alone produced an increase of nitrotyrosine, ICAM-1, VCAM-1, and E-selectin plasma levels in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters, but reduced the effect on adhesion molecules and nitrotyrosine, which was observed during every different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations in ICAM-1, VCAM-1, E-selectin, and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on ICAM-1, VCAM-1, and E-selectin plasma levels, suggesting oxidative stress as a common mediator of such effects. Simvastatin shows a beneficial effect on oxidative stress and the plasma levels of adhesion molecules, which may be ascribed to a direct effect in addition to the lipid-lowering action of the drug.
Ceriello
Antoniom
A
Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy. antonio.ceriello@dpmsc.uniud.it
Quagliaro
Lisa
L
Piconi
Ludovica
L
Assaloni
Roberta
R
Da Ros
Roberto
R
Maier
Amabile
A
Esposito
Katherine
K
Giugliano
Dario
D
D015992:Body Mass Index; D018592:Cross-Over Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D019518:Postprandial Period; D019821:Simvastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D019040:E-Selectin; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D019821:Simvastatin