Endothelial dysfuncton and 2 type diabetes: novel markers for earlier diagnostics

Abstract

Aim. To assess clinical significance of the novel ultrasound and biochemical markers of endothelial dysfunction (ED) in men with 2 type diabetes (DM2).Material and methods. Totally, 200 males studied, with DM2, of those 112 selected (mean age 51,7±6,7 y.) with normal vascular reactivity by Celermajer D. (1994). function of endothelium was assessed by ultrasound study of arterial vessel reactivity of brachial artery (BA) during the test with reactive hyperaemia and proteomic markers of ED — nitric oxide, endothelial nitric oxide synthase type 3 (NOS3), adhesion molecules ICAM-1, VCAM-1, p-selectin, e-selectin, resistin, osteoprotegerin, immune-enzyme assay. Patients were selected to 2 groups by presence or absence of polymorphism с.582+353_379del gene eNOS3.Results. Regardless the absence of ED signs by standard test with reactive hyperaemia, patients with deletion of 27 pair of nucleotides in 4 intron of non-coding area of eNOS3 gene had increased concentrations of adhesion molecules VCAM-1 by 27% and ICAM-1 by 22,9%, as the decrease of eNOS3 by 55,7%, that followed by slowed maximum vasodilation of BA during the test, comparing to the males not having this polymorphism. The significant positive correlations found of the time of maximum vasodilation development with proteomic markers of ED ICAM-1 and VCAM-1.Conclusion. For the first time, a complex of parameters established — time to maximum BA dilation with increased concentration of proteomic markers ICAM-1, VCAM-1 and decrease of eNOS3 that points on the role of ED earlier than BA diameter changes during the reactive hyperaemia test.

Keywords

• endothelial dysfunction
• 2 type diabetes
• arterial vascular reactivity
• endothelium-dependent vasodilation
• polymorphism of endothelial nitric oxide synthase