Diabetic atherothrombosis: helpful adjunctive therapy.

About 90% of type 2 diabetes is attributed to excess weight, which is present in 1.1 billion adults worldwide, and in westernized urban populations the prevalence of diabetes ranges from 14 to 20%.1 Diabetic patients have more cardiovascular events, which are more severe, with increased morbidity and mortality.2 Diabetes mellitus and the adequacy of glycaemic control by lifestyle and medical therapy affect atherothrombosis via alteration of arterial rheology, the arterial wall substrate and blood thrombogenicity.3,4 The rheology of blood flow in diabetics is worsened by physical obstruction and endothelial dysfunction causing vasoconstriction, which is, in part, worsened by decreased nitric oxide synthesis and increased thromboxane levels. Arterial plaque which is more prone to disruption and provides increased substrate for thrombosis, is worsened by a higher density of activated macrophages, tissue factor and glycosylated collagen in lesions from diabetics vs. non-diabetics. Diabetics have increased blood thrombogenicity, especially when their diabetes is poorly controlled, and often have increased serum fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator and coagulation factors II, V and VII, and increased numbers of glycoprotein receptors on platelets as well as increased D-dimer, von Willebrand factor antigen, anti-plasmin and decreased antithrombin III.3–6 Thus, the problem of increased atherothrombosis with increased cardiovascular events in diabetics is multifactorial but, importantly, is also related to decreased intraplatelet cAMP levels, which contributes to the reduced platelet inhibition following P2Y12 receptor antagonist therapy with clopidogrel in diabetics, i.e. the … *Corresponding author: Tel: +01 904 253 2000, Fax: +01 904 953 2911, Email: chesebrj{at}ummhc.org