Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment.
BACKGROUND
Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate.


RESULTS
Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine 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 endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests.


CONCLUSIONS
This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.
Ceriello
Antonio
A
Department of Pathology and Medicine, Experimental and Clinical, Chair of Internal Medicine, University of Udine, Udine, Italy. Antonio.Ceriello@Dpmsc.uniud.it
Taboga
Claudio
C
Tonutti
Laura
L
Quagliaro
Lisa
L
Piconi
Ludovica
L
Bais
Bruno
B
Da Ros
Roberto
R
Motz
Enrico
E
D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D019518:Postprandial Period; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014664:Vasodilation
D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; C002744:3-nitrotyrosine; D014443:Tyrosine; D019821:Simvastatin