About 100 years ago, insulin was introduced as a clinical treatment for diabetes mellitus, and this dramatically reduced the mortality rate due to diabetic emergencies such as diabetic ketoacidosis. Since then, preventing the onset and progression of vascular complications has become a major goal in the treatment of patients with diabetes. The most obvious laboratory abnormality in patients with diabetes is hyperglycemia, and many in vitro and animal studies have demonstrated that hyperglycemia elicits harmful effects on the cells that comprise the vasculature or those that are involved in the progression of atherosclerosis, through various mechanisms such increased oxidative stress, advanced glycation end-product signaling, and protein kinase C activation.