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Pathogenesis of Macrovascular Disease in the Human Diabetic

Atherosclerosis in the diabetic population tends to occur at an earlier age and with greater severity than in the nondiabetic population. The evidence for this is derived from the reported autopsy and clinical data." In persons with known diabetes, macrovascular disease accounts for about 75% of all deaths, mainly expressing itself as cardiovascular disease.' Despite evidence of striking heterogeneity in the etiology of diabetesthe increased predilection for macrovascular complications is not restricted to any one type of diabetes. Furthermore, as pointed out by Bradley, clinically significant atherosclerotic lesions are frequently unrelated to the duration or severity of overt diabetes and may, in fact, be the presenting feature in individuals who may have had relatively mild diabetes, in the form of impaired glucose tolerance (chemical diabetes), for an uncertain duration. This view is supported by several long-term, prospective surveys," including those from Framingham, Tecumseh, and Bedford. On the other hand, in insulin-dependent diabetics, clinical and histopathologic evidence of accelerated atherosclerosis can be frequently documented after 10 to 15 yr of diabetes, when compared with ageand sexmatched controls.