Irina Khripun

Association of the polymorphism in the androgen receptor gene and endothelial function in men with type 2 diabetes

In recent years, actively studied the effect of androgen deficiency on the cardiovascular system, including endothelial function. Genomic effects of testosterone caused by the length of CAG repeats polymorphism in the androgen receptor (AR) gene. Aim . To examine the association of the polymorphism in the AR gene and carbohydrate, lipid metabolism, endothelial function in men with type 2 diabetes. Materials and methods . We examined 88 men, aged 40-65 years (mean age 53±6,4years) with type 2 diabetes. All patients underwent the study of carbohydrate and lipid metabolism, the assessment of vasomotor endothelial function of the brachial artery by ultrasound sonography, were studied biochemical markers of endothelial dysfunction – ICAM-1, VCAM-1, p-selectin, e-selectin, resistin and number of CAG-repeats in the AR gene. Statistical analysis was performed using the application package SPSS 21,0 using regression analysis. Results . The number of CAG repeats had a significant positive regression to the level of total testosterone, a weak negative regression of the number of CAG repeats in the AR gene and lipid metabolism: triglycerides, LDL, atherogenic index. The assessment of the brachial artery ultrasonography revealed negative regression of the baseline brachial artery diameter and blood flow velocity in the endothelium-dependent vasodilation. The number of CAG repeats was significantly correlated with the levels of p-selectin and resistin. Thus, increasing the number of CAG repeats in the AR gene via a weakening of sensitivity to androgens leads to disruption of endothelial function in men with type 2 diabetes. Increasing the number of CAG repeats in the AR gene leads to deterioration of linear flow velocity during the test with reactive hyperemia with increasing production of p-selectin and resistin. Conclusions . The number of CAG repeats in the AR gene can be regarded as a predictor of the development and progression of cardiovascular lesions in men with type 2 diabetes.

Influence of testosterone substitution on glycemic control and endothelial markers in men with newly diagnosed functional hypogonadism and type 2 diabetes mellitus: a randomized controlled trial

Abstract Effects of testosterone (T) on the cardiovascular system of men remain controversial. The impact of T-replacement therapy (TRT) in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) has to be elucidated. This study included 80 men (mean age 51.5 ± 6.3 years) with newly diagnosed T2DM (according to ADA criteria) and functional hypogonadism (according to EAU criteria). Randomization: Group1 (n = 40): TRT using 1%-transdermal T-gel (50 mg/day), Group2 (n = 40) no TRT (controls). Dietary treatment applied to both. Parameters at baseline/after 9 months: anthropometric parameters, lipids and indicators of carbohydrate metabolism (fasting glucose, insulin, HbA1c, HOMA-IR), markers of adipose tissue and EnD (leptin, resistin, p- and e-selectin, ICAM- 1, VCAM- 1 and CRP). ANCOVA for repeated measurements revealed TRT to cause a significant decrease in waist circumference (WC), HOMA-IR and HbA1c vs controls (p < .001, p = .002, p = .004, respectively). Leptin declined in subjects receiving TRT vs controls (p = .04). Concentrations of resistin, ICAM-1, p-selectin and CRP decreased significantly vs controls (all p < .001); no effects for e-selectin and VCAM-1. Advanced age attenuated effects, higher delta testosterone levels augmented effects. Decrement of WC was related to decreasing markers of adipose tissue secretion/EnD. TRT in men with functional hypogonadism and T2DM improved carbohydrate metabolism and markers of endothelial dysfunction.

Could erectile dysfunction in type 2 diabetes change the presumption of normative total blood serum testosterone

155 13. Amer M. D., Hedlund E., Rochester J., Caplan M. S. Platelet-activating factor concentration in the stool of human newborns: effects of enteral feeding and neonatal necrotizing. Biol. Neonate. 2004;85(3):159-166. 14. Eaton S., Rees C. M., Hall N. J. Current research in necrotizing enterocolitis. Early Hum Dev. 2016;97:33-39. doi:10.1016/j.earlhumdev.2016.01.013 15. Minaev S. V., Isaeva A. V., Tovkan E. A., Gudiev Ch. G., Timofeev S. I. et al. The prognostic value of bactericidal/ permeability-increasing protein in infants with congenital pathology of the gastrointestinal tract. Meditsinskii Vestnik Severnogo Kavkaza. – Medical News of North Caucasus. 2014;9(2):116-119. doi:10.14300/ mnnc.2014.09032 16. Siggers R. H., Siggers J., Thymann T., Boye M., Sangild P. T. Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis. J Nutr Biochem. 2011;22(6):511521. doi: 10.1016/j.jnutbio.2010.08.002 17. Watkins D.J., Besner G.E. The role of the intestinal microcirculation in necrotizing enterocolitis. Semin. Pediatr. Surg. 2013;22:83-87. doi: 10.1007/s00383015-3697-9