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 microM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P less than 0.01). PA was further increased in patients with advanced Rd (P less than 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma beta-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P less than 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 less than 0.05), yet more so in patients with Rd (P less than 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 less than 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

A new look at the heart in diabetes mellitus: from ailing to failing

“…6). Plasma concentrations of von Willebrand factor protein are also closely correlated with ADP-induced platelet aggregation in vitro [98]. .…”

“…Relative and absolute measures of regional myocardial blood flow can be obtained [111]. Positron emission tomography has been reported to detect coronary artery disease with a sensitivity of 92 % and a specificity of 89 % [98]. Preferably, resting myocardial perfusion scintigraphy is combined with exercise testing to unmask reduced myocardial blood flow reserve [111].…”

“…Apart from NO a huge array of substances is released from endothelial cells upon activation, e. g. angiotensin II, endothelin 1, TGFb, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1, prostaglandins (all of which are presumably important for diabetic vasculopathy) and von Willebrand factor protein which among other effects facilitates platelet adhesion to the vessel wall [124]. Von Willebrand factor protein has been used as a surrogate marker of endothelial cell activation [98]. The 10-year follow-up results of the Munich General Practitioner Project have shown that the concentration of von Willebrand factor protein in plasma is an independent, prospective predictor of macrovascular death in Type II diabetic patients, both with and without detectable macrovascular disease at baseline [125].…”

von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.

“…vWF is released when endothelial cells are damaged (16). vWF levels are higher in diabetic patients than in control subjects (18,(21)(22)(23), and the levels are even higher among diabetic patients with clinical nephropathy or retinopathy (17)(18)(19)(20)23). Qualitative abnormalities of vWF antigen and changes in the proportion of high-molecular weight multimers have also been reported in diabetes (17)(18)(19)(20)(21).…”

“…Interestingly, a small study suggested that increased vWF was associated with the development of microalbuminuria in type 1 diabetes but not with the development of retinopathy (32). However, vWF levels have been reported to be higher in diabetic patients with retinopathy compared with control subjects or diabetic patients without retinopathy (19,23).…”