Takahisa Deguchi, Raymond L. Rosales, Teruto Hashiguchi and Kimiyoshi Arimura
Although pathologically not necessarily the same, germane to both diabetic neuropathy and peripheral vascular disease is the morbid vascular complication of diabetes mellitus. As it appears, strict glycemic control alone is unable to neither prevent nor promote recovery of diabetic microvascular complications, thus the need to seek other treatment strategies. In addressing the vascular complications, a unitary approach between diabetic neuropathy, peripheral vascular disease and antiplatelet therapy is in order. Notably, the fine balance between platelet/coagulation and fibrinolysis systems are dominantly shifted to acceleration of the platelet/coagulation system in diabetes mellitus. Not only platelet homophilic aggregation, but also platelet heterophilic aggregation with neutrophils or monocytes in inflammatory conditions is observed. Hyperglycemia also induces overproduction of reactive oxygen species by multiple pathomechanisms that injure endothelial cells and reduce nitric oxide which eventually reduce the blood flow in microvessels. Among other antiplatelet agents, cilostazol is a novel antiplatelet agent that has been found to have beneficial effects in macrovascular events like stroke and peripheral vascular diseases. In peripheral vascular disease clinical trials, there is robust data that cilostazol is efficacious in improving walking speed. Also, cilostazol increases nerve blood flow/nerve conduction, and inhibits reduction in pericyte area of endoneurial microvessels in animal models of diabetic neuropathy. Clinical trials on diabetic polyneuropathy alone or in combination with peripheral vascular disease indicate clinical improvement in blood flow, but not necessarily in neuropathy parameters. Since a neurodegenerative process is equally as important a pathomechanism, the effect of antiplatelet therapy in diabetic neuropathy should be examined in long-term clinical trials that may potentially unfold its benefits over time.
