Platelet Enzyme Activities in Diabetes Mellitus in Relation to Endothelial Damage

Abstract

Increased platelet reactivity has been suggested in the pathogenesis of both arteriosclerosis and diabetic microangiopathy. Therefore, platelet function and platelet enzyme activities were assessed in a large group of 357 diabetics (256 patients with IDDM, aged 16–49 and 101 patients with NIDDM, aged 50–78) and 163 matched controls, and related to photographically documented retinopathy (Rd) and to peripheral vascular disease (PVD) as well as to plasma levels of von Willebrand factor (VIII R:Ag) as an indicator of endothelial damage. Patients with IDDM had increased platelet aggregation (PA, expressed as μM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P < 0.01). PA was further increased in patients with advanced Rd (P < 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma β-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P < 0.05), as was malondialdehyde (MDA) production of platelets (as a measure of platelet endoperoxide formation). Factor VIII-related antigen in plasma was already increased in patients without Rd (P < 0.05), yet more so in patients with Rd (P < 0.01). Prostacyclin-stimulated adenylate cyclase activity (ACA) of platelets (as an antiaggregatory enzyme system) was twice as high in diabetics with advanced Rd compared with patients without Rd and with controls (P < 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets. Increased PA was also found in subjects with NIDDM (P < 0.05). Patients with PVD, however, did not differ from patients without PVD when subjects with Rd were excluded. These results indicate that increased platelet activity may precede clinically detectable vascular disease, but is associated with increased levels of plasma von Willebrand factor protein, suggesting that endothelial damage is already present. Increases of PA platelet enzyme activities and plasma von Willebrand factor are particularly prominent in diabetics with Rd, reflecting highly active and perhaps younger platelets in this condition.