Carotid atherosclerosis (CA) and, especially, carotid artery stenosis (CAS), are associated with a high risk of cardiovascular events in subjects with type 2 diabetes (T2D). In this study, we aimed to identify risk factors and biomarkers of subclinical CA and CAS in T2D individuals. High-resolution ultrasonography of carotid arteries was performed in 389 patients. Ninety-five clinical parameters were evaluated, including diabetic complications and comorbidities; antihyperglycemic, hypolipidemic, and antihypertensive therapy; indices of glycemic control and glucose variability (GV); lipid panels; estimated glomerular filtration rate (eGFR); albuminuria; blood cell count; and coagulation. Additionally, serum levels of calponin-1, relaxin, L-citrulline, and matrix metalloproteinase-2 and -3 (MMP-2, -3) were measured by ELISA. In univariate analysis, older age, male sex, diabetes duration, GV, diabetic retinopathy, chronic kidney disease, coronary artery disease, peripheral artery disease, and MMP-3 were associated with subclinical CA. In addition to these factors, long-term arterial hypertension, high daily insulin doses, eGFR, and L-citrulline were associated with CAS. In multivariate logistic regression, age, male sex, BMI, GV, and eGFR predicted CA independently; male sex, BMI, diabetes duration, eGFR, and L-citrulline were predictors of CAS. These results can be used to develop screening and prevention programs for CA and CAS in T2D subjects.

Among the reasons of primary lymphedema development, a certain role belongs to genetic factors. The specific molecular products participate in remodeling of blood and lymphatic vascular networks. Vascular endothelial growth factors (VEGFs) are key regulators of endothelial functions of the cells, which are responsible for lympho- and vasculogenesis. Moreover, matrix metalloproteinases (ММР) may act as regulators of both lymphangiogenesis, and angiogenesis. Since the regulatory regions of VEGFA gene, as well as of ММР genes are polymorphic, one may suggest, that their different expression level, determined by these polymorphisms, could be associated with development of swellings typical for lymphedema.We have analyzed gene polymorphisms in two regulatory regions of vascular endothelial growth factor-A VEGF-A (rs 699947 and rs 3025039), and matrix metalloproteinase genes MMP2 (rs 2438650), MMP3 (rs 3025058), MMP9 (rs 3918242), and their combinations in the patients with primary lymphedema.A group of patients with primary lymphedema included 72 subjects (55 women and 17 men) at the age of 18 to 81 years. Control group included 526 inhabitants of Novosibirsk (153 men, 373 women) without chronic diseases, comparable for age with lymphedema patients. We have performed typing of regulatory regions in VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 genes (rs 3918242). Fifteen complex genotypes have been revealed that were positively associated with disease. Analysis of the gene network topology has outlined the main intergenic interactions upon primary lymphedema development. MMP2 -1306 CC, MMP9 -1562CC and VEGF +936CC arrange the basic knots in the gene network (53% of total interactions). A number of significantly different complex genotypes was revealed at patients with primary lymphedema with normal body mass index (BMI < 25) and obesity (BMI < 30). Hence, frequency of complex genotype VEGF +936 CC: MMP3 -1171 5А6А:MMP9 -1562 CC in the patients with obesity is increased more 5.5-fold compared to the patients with normal BMI.The data obtained may presume a certain value of the analyzed gene polymorphisms in pathogenesis of primary lymphedema. Topological analysis of gene networks allows to study the structural and functional organization of gene-gene interactions for development of approaches to individyal preventive maintenance and therapy of the disease.