PLATELETS, VASCULAR-DISEASE, AND DIABETES-MELLITUS

Diabetes is associated with increased risk for atherosclerosis and its thromboembolic complications. Theories about mechanisms of atheroscle rosis in diabetes are similar to those in the nondiabetic population. Platelets contribute to atherosclerosis through effects on vessels by materials released from the platelets, which interact with injured or altered vessels. In diabetes, platelets could contribute to enhanced a therosclerosis through hypersensitivity to agonists at sites of vessel injury and increased release of materials from adherent platelets. Di abetic platelets are hypersensitive to agonists in vitro, and alterati ons in a number of mechanisms involved in platelet activation occur in these platelets, which could contribute to the hypersensitivity. Thes e alterations include increased presence of gIycoprotein receptors for agonists and adhesive proteins on the platelet surface, increased fib rinogen binding, decreased membrane fluidity, enhanced arachidonate pa thway activation with increased thromboxane A(2) formation, and increa sed phosphoinositide turnover leading to increased inositol trisphosph ate production, Ca2+ mobilization, and protein phosphorylation. There is some evidence for increased platelet activity in vivo in diabetes, but it is unclear whether this reflects platelet hypersensitivity or i ncreased platelet turnover on already diseased vessels. Studies in dia betic animals indicate greater interaction of platelets with injured v essels and incorporation into experimentally induced thrombi, but it i s unclear if this reflects changes in platelets or other factors. Thes e changes could be contributing to the enhanced atherosclerosis and it s clinical complications in diabetic patients.