Patients with diabetes, particularly those with macrovascular disease, have an increased circulating platelet mass secondary to increased ploidy of megakaryocytes. In addition, platelets isolated from the blood of subjects with diabetes exhibit impaired capacity to mediate vasodilatation, apparently because of release of a short-acting platelet-derived substance(s) that interferes with the ADP-induced dilatory response seen in normal vessels with intact endothelium.
Platelets from diabetic subjects demonstrate increased reactivity. They exhibit increased degranulation and increased aggregation in response to diverse stimuli. In addition, the procoagulant capacity of platelets from subjects with diabetes mellitus is increased. Thus, the generation of coagulation factor Xa and of thrombin is increased by three- to sevenfold in samples of blood containing platelets from diabetic as opposed to nondiabetic subjects.
One potential mechanism responsible for the increased platelet reactivity associated with diabetes is decreased membrane fluidity, potentially reflecting increased glycation of platelet membrane proteins. A reduction in membrane fluidity occurs when platelets from normal subjects are incubated in media containing concentrations of glucose similar to those seen in blood from subjects with poorly controlled diabetes. Because membrane fluidity is likely to alter membrane receptor accessibility by ligands, reduced membrane fluidity may contribute to the predisposition to activation of platelets. Accordingly, improved gly-cemic control and consequently decreased glycation of membrane proteins may increase membrane fluidity and decrease hyperreactivity. In fact, we have found that treatment with insulin is associated with an increased risk of high platelet reactivity. Accordingly, it appears that both metabolic control and a focus on optimal hormonal balance modification of insulin resistance and diminution of the often associated hyper(pro)insulinemia are needed to attenuate increased platelet reactivity.
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