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

Antonio Ceriello, Claudio Taboga, Laura Tonutti, Lisa Quagliaro, Ludovica Piconi, Bruno Bais, Roberto Da Ros, Enrico Motz

Research output: Contribution to journalArticle

538 Citations (Scopus)

Abstract

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. Methods and 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.

Original languageEnglish
Pages (from-to)1211-1218
Number of pages8
JournalCirculation
Volume106
Issue number10
DOIs
Publication statusPublished - Sep 3 2002

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Cohort Effect
Simvastatin
Hypertriglyceridemia
Hyperglycemia
Oxidative Stress
Fats
Meals
Glucose
Lipids
Therapeutics
Triglycerides
Cardiovascular Diseases
Placebos
3-nitrotyrosine
Pharmaceutical Preparations

Keywords

  • Cardiovascular diseases
  • Diabetes mellitus
  • Endothelium
  • Lipids
  • Stress

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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. / Ceriello, Antonio; Taboga, Claudio; Tonutti, Laura; Quagliaro, Lisa; Piconi, Ludovica; Bais, Bruno; Da Ros, Roberto; Motz, Enrico.

In: Circulation, Vol. 106, No. 10, 03.09.2002, p. 1211-1218.

Research output: Contribution to journalArticle

Ceriello, Antonio ; Taboga, Claudio ; Tonutti, Laura ; Quagliaro, Lisa ; Piconi, Ludovica ; Bais, Bruno ; Da Ros, Roberto ; Motz, Enrico. / 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. In: Circulation. 2002 ; Vol. 106, No. 10. pp. 1211-1218.
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AU - Da Ros, Roberto

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N2 - 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. Methods and 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.

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