Circulating dickkopf-1 in diabetes mellitus: Association with platelet activation and effects of improved metabolic control and low-dose aspirin

Background-dickkopf-1 (dkk-1) is a major regulator of the wnt signaling pathway,involved in inflammation,atherogenesis,and the regulation of glucose metabolism. because platelets are major contributors to circulating levels of dkk-1 in other clinical settings,we aimed at characterizing the platelet contribution to dkk-1 in type 2 diabetes mellitus (t2dm) and evaluating associations of dkk-1 with glucose metabolism,platelet activation,and endothelial dysfunction. methods and results-a cross-sectional comparison of dkk-1,soluble cd40l (scd40l; reflecting platelet-mediated inflammation),asymmetric dimethylarginine (adma; marker of endothelial dysfunction),and urinary 11-dehydro-thromboxane b2 (in vivo marker of platelet activation) was performed among 214 diabetic patients (90 receiving aspirin at 100 mg/day) and 30 healthy controls. plasma dkk-1 levels were markedly higher in patients with t2dm than in healthy patients (p<0.0001). dkk-1 levels were significantly lower in diabetic patients receiving compared with those not on aspirin treatment (p=0.008); in the latter,dkk-1 was significantly correlated with 11-dehydro-thromboxane b2,adma,and cd40l (q=0.303. p<0.0001,q=0.45. p<0.0001,and q=0.37,p<0.0001,respectively) but not with glycemic control or dm duration. among patients not receiving aspirin,improvement of metabolic control in a subgroup of newly diagnosed patients treated with acarbose for 20 weeks and in a group treated with rosiglitazone for 24 weeks was associated with concurrent significant reductions in dkk-1 (p=0.005 and p=0.004) and 11-dehydro-thromboxane b2 (p=0.005 and p=0.004). conclusions-circulating dkk-1 is increased in t2dm and associated with endothelial dysfunction and platelet activation. plasma dkk-1 levels are reduced with improvement of glycemic control and low-dose aspirin treatment. © 2014 the authors.