Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:816-823
Published online before print February 19, 2004, doi: 10.1161/01.ATV.0000122852.22604.78
Published online before print February 19, 2004, doi: 10.1161/01.ATV.0000122852.22604.78
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© 2004 American Heart Association, Inc.
Brief Reviews |
Is Oxidative Stress the Pathogenic Mechanism Underlying Insulin Resistance, Diabetes, and Cardiovascular Disease? The Common Soil Hypothesis Revisited
From Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Italy.
Correspondence to Antonio Ceriello, Chair of Internal Medicine, University of Udine P. le S. Maria della Misericordia, 33100 Udine, Italy. E-mail ceriello{at}uniud.it
Type 2 diabetes is a worldwide increasing disease resulting from the interaction between a subject’s genetic makeup and lifestyle. In genetically predisposed subjects, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When beta cells are no longer able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance appears, characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These 3 conditions, ie, insulin resistance, impaired glucose tolerance, and overt diabetes, are associated with an increased risk of cardiovascular disease. Because all these conditions are also accompanied by the presence of an oxidative stress, this article proposes oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both beta cells and endothelium, eventually leading to overt diabetes and cardiovascular disease. This hypothesis, moreover, may also contribute to explaining why treating cardiovascular risk with drugs, such as calcium channel blockers, ACE inhibitors, AT-1 receptor antagonists, and statins, all compounds showing intracellular preventive antioxidant activity, results in the onset of new cases of diabetes possibly being reduced.
Key Words: oxidative stress • insulin resistance • impaired glucose tolerance • diabetes • cardiovascular disease
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