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(Circulation. 2005;111:2518-2524.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients

Antonio Ceriello, MD; Roberta Assaloni, MD; Roberto Da Ros, MD; Amabile Maier, MD; Ludovica Piconi, BSc; Lisa Quagliaro, BSc; Katherine Esposito, MD; Dario Giugliano, MD

From the Department of Pathology and Medicine, Experimental and Clinical, Chair of Internal Medicine, University of Udine, Udine (A.C., R.A., R.D.R., A.M.); Morpurgo-Hofman Research Laboratory on Aging, Udine (L.P., L.Q.); and Department of Geriatric and Metabolic Diseases, Second University of Naples, Naples (K.E., D.G.), Italy.

Correspondence to Professor Antonio Ceriello, Chair of Internal Medicine, University of Udine, P. le S. Maria della Misericordia, 33100 Udine, Italy. E-mail ceriello{at}uniud.it

Received August 10, 2004; revision received January 12, 2005; accepted January 26, 2005.

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.

Key Words: endothelium • hyperglycemia • inflammation • oxidative stress

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