Clinical relevance of the oxidative stress concept

Subjects with type 2 diabetes have markedly increased rates of coronary heart disease (CHD) that are only partly explained by the increased levels of conventional cardiovascular risk factors such as total cholesterol, hypertension, and smoking. Although an increasing number of studies have suggested a role for glycemia in cardiovascular disease, considerable controversy remains. This issue may be resolved when the results of the UK Prospective Diabetes Study (UKPDS) are presented. One possible promising relatively new risk factor that may explain high levels of CHD in diabetic subjects is increased oxidative stress. Type 2 diabetic subjects have an increased preponderance of small dense low-density lipoprotein (LDL), which predisposes to the oxidation of LDL. Almost all studies show that diabetic subjects have increased oxidative stress. In addition, they may have lower levels of alpha-tocopherol. In most studies, increased oxidative stress has been associated with cardiovascular disease, although prospective data are lacking. If levels of oxidative stress are increased, what are the best levels to reduce it to? Improved glycemic control has been associated with decreased oxidative stress. Antioxidant replacement such as alpha-tocopherol may also be beneficial. Interestingly, some special properties of hypoglycemic agents have been described. Gliclazide has been reported to favorably affect both free radicals and platelet reactivity. Gliclazide may have a more favorable effect on tissue plasminogen activator (tPA) than tolbutamide. In conclusion, increased levels of oxidative stress may underlie some of the increased risk of cardiovascular disease in diabetic subjects. Interventions to decrease levels of oxidative stress by methods such as improved glycemic control, antioxidant therapy (ie, alpha-tocopherol), and gliclazide are indicated.