Oxidative stress and diabetic neuropathy: a new understanding of an old problem

Diabetes has reached epidemic proportions in the Western world. In the United States, 17 million individuals have diabetes, greater than 6% of the population (1). The morbidity and mortality of diabetes is due to the development of both macrovascular and microvascular complications (2). Macrovascular complications including myocardial infarction, stroke, and large vessel peripheral vascular disease are 2 to 4 times more prevalent in individuals with diabetes. The underlying common factor in macrovascular complications is the ability of the diabetic condition to accelerate atherogenesis. Atherogenesis is a multifactorial response of vessels to injury; both insulin resistance and elevated lipid levels, common in diabetes, are primary triggers of atherogenic injury (3). The endothelium in diabetic arteries is also more prone to atherogenic injury, likely due to decreased production of endothelial nitric oxide, known to be antiatherogenic, and increased production of plasminogen activator inhibitor-1 (PAI-1) (4). While macro-vascular complications are common among diabetics, diabetes-specific microvascular complications will eventually affect nearly all individuals with diabetes. Diabetic retinopathy is the most common cause of adult blindness in the United States. Ninety percent of diabetics present evidence of retinopathy within 15 years of disease onset and approximately 25,000 new cases of diabetes-related blindness are reported per year (5). Diabetes is also the leading cause of renal failure in the United States, accounting for 40% of new cases each year (6). Greater than half of all patients with diabetes develop neuropathy, a progressive deterioration of nerves resulting in peripheral and autonomic nerve dysfunction. As a result, diabetic neuropathy is the most common cause of nontraumatic amputations and autonomic failure (7, 8). In his or her lifetime, a diabetic patient with neuropathy has a 15% chance of undergoing one or more amputations (9).