Increased Intraplatelet ADMA Level May Promote Platelet Activation in Diabetes Mellitus

Abstract

Background. Antiplatelet therapy has become a standard therapeutic approach in the secondary prevention of cardiovascular system disorders of thrombotic origin. Patients with concomitant diabetes mellitus (DM) obtain fewer benefits from this treatment. Hence, the pathophysiology of altered platelet function in response to glucose metabolism impairment should be of particular interest. Objectives. The aim of our study was to verify if the platelet expression of the asymmetric dimethylarginine (ADMA) in diabetic patients differs in comparison to the nondiabetic ones. The correlation of platelet-ADMA with platelet activation and aggregation as well as with other risk factors was also investigated. Material and Methods. A total of 61 subjects were enrolled in this study, including thirty-one type 2 diabetic subjects without diabetes-related organ damage. Physical examination was followed by blood collection with an assessment of platelet aggregation, traditional biochemical cardiovascular risk factors, and evaluation of nitric oxide bioavailability parameters in plasma and thrombocytes. Subsequently, the assessment of endothelial function using Peripheral Arterial Tonometry and Laser Doppler Flowmetry (LDF) was performed. Results. In the DM group, elevated concentration of intraplatelet ADMA and higher ADMA/SDMA ratio compared to the control group was observed. It was accompanied by higher ADP-mediated platelet aggregation and lower microvascular response to a local thermal stimulus measured by LDF in the diabetes group. Conclusions. Type 2 diabetes is related to higher intraplatelet concentration of asymmetric dimethylarginine (ADMA), which may result in impaired platelet-derived nitric oxide synthesis and subsequent increased platelet activity, as assessed by the ADP-induced aggregation. Laser Doppler Flowmetry, compared to EndoPAT 2000, appears to be a more sensitive indicator of the impaired microvasculature vasodilation in diabetics without the presence of clinically significant target organ damage.