Intensive Glucose Lowering and Cardiovascular Disease Prevention in Diabetes

Abstract

Cardiovascular disease (CVD) is a very common, if not the most common, cause of morbidity and mortality in developed countries, and there has been longstanding recognition that diabetes is a potent risk factor for CVD.1,–,3 Individuals with either type 1 or type 2 diabetes mellitus manifest CVD rates up to 4 to 10 times higher than those observed in nondiabetic subjects. Subjects with diabetes also have been shown to have more advanced atherosclerosis, as measured by carotid intima-media thickness (CIMT) measures or coronary artery calcium (CAC) scores.4,–,7 The potential pathophysiology of accelerated atherosclerosis and CVD risk in diabetes is complex8 (Table 1). Patients with type 2 diabetes mellitus commonly have hypertension and manifest a number of abnormalities in systemic lipoprotein metabolism and in inflammatory and coagulation pathways that are predicted to be proatherogenic and to increase CVD risk on the basis of observational and mechanistic studies conducted in diabetic and nondiabetic experimental models. These abnormalities are related to coexisting insulin resistance in the majority of patients with diabetes and manifest as low high-density lipoprotein cholesterol, increased triglyceride-rich lipoprotein cholesterol, postprandial lipemia, elevated levels of C-reactive protein and other inflammatory markers, and increased levels of plasminogen activator inhibitor 1 and fibrinogen levels. Insulin resistance in patients with type 2 diabetes mellitus is generally but not always related to obesity and may be more specifically linked to central obesity and accumulation of fat in the visceral fat depot.9,10 View this table: Table 1. Potential Contributors to Accelerated Atherosclerosis and CVD in Diabetes In patients with type 1 diabetes mellitus, understanding of the potential pathophysiologies for accelerated atherosclerosis and CVD is complicated by the young age (usually before the second or third decade of life) of these patients at the time of diagnosis of …