Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients

Circulation. 2005 May 17;111(19):2518-24. doi: 10.1161/01.CIR.0000165070.46111.9F. Epub 2005 May 2.

Abstract

Background: Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction and inflammation through oxidative stress. Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function.

Methods and results: Twenty type 2 diabetic patients ate 3 different test meals: a high-fat meal, 75 g glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, endothelial function, nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 were assayed during the tests. Subsequently, diabetics took atorvastatin 40 mg/d, irbesartan 300 mg/d, both, or placebo for 1 week. The 3 tests were performed again between 5 and 7 days after the start of each treatment. High-fat load and glucose alone produced a decrease in endothelial function and increases in nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6. These effects were more pronounced when high-fat load and glucose were combined. Short-term atorvastatin and irbesartan treatments significantly counterbalanced these phenomena, and their combination was more effective than either therapy alone.

Conclusions: This study confirms an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function and inflammation, suggesting oxidative stress as a common mediator of such an effect. Short-term treatment with atorvastatin and irbesartan may counterbalance this phenomenon; the combination of the 2 compounds is most effective.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Anticholesteremic Agents / administration & dosage
  • Atorvastatin
  • Biphenyl Compounds / administration & dosage*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / pathology*
  • Female
  • Heptanoic Acids / administration & dosage*
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / pathology
  • Hypertriglyceridemia / complications
  • Hypertriglyceridemia / pathology
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Irbesartan
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Postprandial Period
  • Pyrroles / administration & dosage*
  • Tetrazoles / administration & dosage*
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Biphenyl Compounds
  • Heptanoic Acids
  • Pyrroles
  • Tetrazoles
  • Atorvastatin
  • Irbesartan