Effect of testosterone on endothelial function in men with type 2 diabetes mellitus

Abstract

Objective: to study the effect of testosterone (T) levels on laboratory and instrumental markers of endothelial dysfunction (ED). Materials and methods: the study included 276 male patients with type 2 diabetes mellitus (DM). General clinical studies were carried out, analysis of parameters of carbohydrate metabolism, the content of hormones (total T, SHBG, free T, estradiol, LH, FSH, prolactin, TSH, DHEA) were performed. Endothelial secretory function was assessed using markers such as: nitric oxide (NO), endothelial NO synthase type 3, endothelin, ICAM-1, VCAM-1, p- and e-selectins, cadherin, PAI-1, VEGF-1. Additionally, the content of biologically active substances affecting endothelial function was studied: homocysteine B, C-reactive protein (CRP), osteoprotegerin, leptin, resistin, adiponectin. The vasomotor function of the endothelium was assessed by ultrasound examination of the endothelium-dependent vasodilation (EDVD) of the brachial artery (BA) during the reactive hyperemia test; in addition, the thickness of the intima-media complex (TIM) of the carotid arteries was measured. Correlation analysis was performed using Spearman’s method. Results: the level of total T is interrelated with the instrumental parameters of the endothelial function: the TIM of the carotid arteries (r = -0.26; p = 0.009), the time of maximum BA vasodilation development (r = -0.41; p <0.001), EDVD (r = 0 , 28; p = 0.004), as well as laboratory markers of ED: ICAM-1 (r = -0.45; p <0.001), VCAM-1 (r = -0.29; p <0.001), cadherin (r = -0.36; p <0.001), NO (r = 0.32; p = 0.002), VEGF (r = -0.23; p = 0.001), CRP (r = -0.29; p <0.001) and adipohormones: leptin (r = -0.26; p = 0.01), resistin (r = -0.24; p <0.001) and adiponectin (r = 0.28; p = 0.007). Conclusion: T deficiency is associated with a deterioration in the vasomotor function of the endothelium: a decrease in EDVD along with an increase in the time of maximum BA vasodilation development and impaired endothelial secretory function: an increase in the concentrations of VCAM-1, ICAM-1, cadherin, VEGF and, on the contrary, a decrease in NO levels. A decrease in T levels is accompanied by an increase in the content of CRP, resistin, leptin and a decrease in adiponectin, which aggravates the dysfunction of the endothelium.