Features of Diabetic Macrovascular Disease

Unlike microvascular disease, which occurs only in patients with diabetes, macrovascular disease resembles that in subjects without diabetes. However, subjects with diabetes have more rapidly progressive and extensive cardiovascular disease, with a greater incidence of multivessel disease and a greater number of diseased vessel segments than nondiabetic persons (20). In both subjects with and without diabetes, atherosclerosis begins with endothelial dysfunction that results from injury caused by many factors, including hyperglycemia (21). Endothelial injury increases the adhesiveness of the endothelium with respect to leukocytes and platelets, as well as its permeability to lipoproteins and other plasma constituents. A number of studies have shown that elevated glucose levels and/or glucose-derived advanced glycation end products (AGEs) induce the expression of monocyte chemotactic protein 1 (MCP-1) (22) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular-cell adhesion molecule-1 (VCAM-1) in vascular cells (23-28). These specific molecules induce the adherence, migration, and accumulation of monocytes and T-cells on the endothe-lium and stimulate the infiltration of these cells into the subendothelial space. After infiltration, monocytes become macrophages and form foam cells. Progression beyond the first step of atherogenesis is associated with subsequent migration, lipid accumulation, and foam-cell formation of smooth muscle cells. The persistence of these changes causes more advanced, complex, lesions of atherosclerosis. These lesions are covered by a fibrous cap, which forms as a result of increased activity of platelet-derived growth factor, TGF-P , interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), osteo-pontin, and matrix metalloproteinases (MMPs). Rupture of this fibrous cap by MMPs and consequent thrombosis may lead to the acute coronary syndrome (29-31). Hyperglycemia and/or hyperglycemia-induced AGEs have been shown to induce TGF-P (32,33), IL-1 (34,35), TNF-a (36,37), osteopontin (38), and MMP9 (39).

Your Heart and Nutrition

Your Heart and Nutrition

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