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


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.
Ceriello
Antonio
A
Department of Pathology and Medicine, Experimental and Clinical, Chair of Internal Medicine, University of Udine, Udine, Italy. ceriello@uniud.it
Assaloni
Roberta
R
Da Ros
Roberto
R
Maier
Amabile
A
Piconi
Ludovica
L
Quagliaro
Lisa
L
Esposito
Katherine
K
Giugliano
Dario
D
D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology; D015228:Hypertriglyceridemia / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D019518:Postprandial Period; D011758:Pyrroles / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011758:Pyrroles; D013777:Tetrazoles; D000069059:Atorvastatin; D000077405:Irbesartan