Diabetes Mellitus as a Risk Factor for Development of Vulnerable (Unstable) Coronary Plaque: A Review of Possible Mechanisms

The prevalence of early and severe atherosclerotic coronary disease is much higher in diabetic patients than in their nondiabetic counterparts. The incidence of acute coronary syndrome is also disproportionately higher in this population. This difference has generally been attributed to a much higher prevalence of traditional risk factors such as hypertension and dyslipidemias in diabetic patients; however, a clear explanation is yet to be found. Vascular injury and growth factors are increased in these individuals. Metabolic and biochemical abnormalities such as glycosylation and oxidation of low density lipoprotein (LDL) and the formation of "large" very low density lipoprotein (VLDL) promote the accumulation of monocytes and macrophages, leading to the formation of foam cells. Glycosylation of high density lipoprotein (HDL) impairs its antiatherogenic action. These abnormalities may enhance the extracellular (core) lipid content of the atherosclerotic plaque, rendering it softer. An augmented inflammatory response also appears to take place in the atherosclerotic plaque of diabetic patients. There is a strong chemotaxis for monocytes and macrophages mediated by glycoxidation. These cells induce the secretion of interleukin-1 and cachectin/tumor necrosis factor, which in turn inhibit nitric oxide activity, leading to detrimental action of mast cells. Diabetic patients also have an enhanced vasoconstrictive response. Significant platelet, coagulation, and fibrinolytic abnormalities are also present in these individuals, which favor a relatively hypercoagulable state. Plaque stress due to enhanced tensile and compression forces appears to be increased in diabetic patients.