Protein kinase Cbeta isoform inhibitors: a new treatment for diabetic cardiovascular diseases.

The center of the pandemic of diabetes is the lifethreatening cardiovascular complications that can be categorized into macrovasculopathy, microvasculopathy, and diabetic cardiomyopathy. Macrovasculopathy affects large vessels and manifests as atherosclerosis and the subsequent coronary artery disease, peripheral artery disease, and cerebrovascular disease. Atherosclerosis and its related complications are responsible for most of the mortality in diabetic patients.1 Indeed, diabetes has been firmly established as an independent risk factor for atherosclerosis. This risk seems to precede the onset of type 2 diabetes but begins with hyperglycemia in patients with type 1 diabetes.2 Multiple factors in diabetes—including insulin resistance, dyslipidemia, elevated free fatty acid, and hypertension—increase the risk. Many clinical surveys, such as the Framingham Study, have shown that the incidence of carotid artery disease is increased 2to 4-fold in patients with diabetes or insulin resistance. When intima-media thickness is used as the indicator for the severity of atherosclerosis, both type 13,4 diabetes and type 25 diabetes are associated with more advanced atherosclerosis when compared with ageand sex-matched controls. This association could also be related to hyperglycemia because intensive euglycemic control has been shown to reduce the progression of intima-media thickness in the Epidemiology of Diabetes Interventions and Complications study, which involves 1229 patients.6 These clinical data suggest that hyperglycemia itself, in addition to the aforementioned established risk factors such as dyslipidemia, hypertension, insulin resistance, and oxidative stress, might have an independent role in the acceleration of atherosclerosis.