Clinical relevance of the oxidative stress concept

Subjects with type 2 diabetes have markedly increased rates of coronary hea rt disease (CHD) that are only partly explained by the increased levels of conventional cardiovascular risk factors such as total cholesterol, hyperte nsion, and smoking. Although an increasing number of studies have suggested a role for glycemia in cardiovascular disease, considerable controversy re mains. This issue may be resolved when the results of the UK Prospective Di abetes Study (UKPDS) are presented. One possible promising relatively new r isk factor that may explain high levels of CHD in diabetic subjects is incr eased oxidative stress. Type 2 diabetic subjects have an increased preponde rance of small dense low-density lipoprotein (LDL), which predisposes to th e oxidation of LDL. Almost all studies show that diabetic subjects have inc reased oxidative stress. In addition, they may have lower levels of alpha-t ocopherol. In most studies, increased oxidative stress has been associated with cardiovascular disease, although prospective data are lacking. If leve ls 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 benef icial. Interestingly, some special properties of hypoglycemic agents have b een described. Gliclazide has been reported to favorably affect both free r adicals and platelet reactivity. Gliclazide may have a more favorable effec t on tissue plasminogen activator (tPA) than tolbutamide. In conclusion, in creased levels of oxidative stress may underlie some of the increased risk of cardiovascular disease in diabetic subjects. Interventions to decrease l evels of oxidative stress by methods such as improved glycemic control, ant ioxidant therapy (ie, alpha-tocopherol), and gliclazide are indicated. Copy right (C) 2000 by W.B. Saunders Company.