[Clinical importance of evaluation of circulating miRNA expression and epicardial adipose tissue thickness as predictors of cardiovascular pathology in young patients with type 1 diabetes mellitus].

Cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM) is preceded by asymptomatic changes in the geometry of the heart. The only symptoms of the beginning of cardiac remodeling and concomitant predictors of an unfavorable cardiovascular prognosis are: thickening of epicardial fat (EAT), secreting a number of adipokines, and cardiospecific miRNAs. To improve the effectiveness of prevention of CVD in young patients with DM1, a search was made for structural-functional and epigenetic markers. AIM: To assess the state of the cardiovascular system according to MRI-heart with T1 mapping in T1DM without CVD. To reveal the relationship of epigenetic markers (circulating miR-126-5p, miR-21-5p) and adipokines with cardiovascular system in T1DM. Suggested personalized approach to patients with T1DM with initial manifestations of joint remodeling and/or exclusion of cardiospecific microRNA. MATERIALS AND METHODS: The study included 40 patients: 30 with T1DM (age 26.2±7.4 years), 10 without T1DM (26.4±8.2). The patients underwent a general clinical examination, bioimpedancemetry, electrocardiography, MRI of the heart with T1 mapping, determination of adiponectin, resistin, visfatin, NT-proBNP, miR-126-5p, miR-21-5p. RESULTS: Patients with T1DM had lower levels of cardioprotective miR-126-5p (p=0.046). According to MRI of the heart in T1DM, signs of vascular remodeling were revealed - thickening of the interventricular septum (p=0.001), posterior wall (p=0.012) and relative size of the walls (p=0.048) of the left ventricle, an increase in EAT density (p=0.001). Diffuse vascular fibrosis was found in 16% of patients from the T1DM group. Also, in T1DM, the expression of visfatin is increased (p=0.036) and adiponectin is reduced (p=0.043). CONCLUSION: Structural and functional changes in the cardiovascular system (including thickening of the EAT), shifts in miR-126-5p expression and adipokines profile are observed already at a young age in patients with T1DM. In T1DM, diffuse vascular fibrosis is detected in 16% of patients. The data obtained were used to identify the group increased risk of developing CVD in T1DM and served as the basis for determining the timing of the start of preventive therapy.

[Features of steroidogenesis and arterial hypertension in men in different types of "physiological" male hyperandrogenism].

AIM: To reveal the peculiarities of steroidogenesis and arterial hypertension in «physiological¼ hyperandrogenism in men. MATERIALS AND METHODS: One-stage simultaneous study. The groups of men with hyperandrogenism caused by increased total testosterone (n=34) and those with hyperandrogenism caused by increased dihydrotestosterone (DHT) (n=66) were compared. In determining the type of hyperandrogenism and allocating patients to groups, DHT and total testosterone levels were determined by enhanced chemiluminescence. Subgroups of men with and without arterial hypertension were compared in the group of patients with hyperandrogenism due to an increase in total testosterone. Body mass index, waist circumference, systolic and diastolic blood pressure, pulse, and LH, SBHG, estradiol, blood multisteroid levels by isotope dilution liquid chromatography/tandem mass spectrometry, glucose, blood lipid spectrum, uric acid, creatinine, renin, potassium, sodium, and blood chloride were assessed in all patients. Patients with arterial hypertension additionally underwent daily BP monitoring, albuminuria assessment, electrocardiography, ocular fundus examination. The baseline threshold level of significance was p<0.05. For multiple comparisons, the p significance level was calculated using the Bonferroni correction. RESULTS: Statistically significant differences were found in the levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione, which were higher in men with elevated levels of total testosterone. No statistically significant differences in other laboratory parameters were found. No cases of increased blood pressure were detected in the group of men with elevated DHT. In the group of men with elevated total testosterone, 23,5% of men with arterial hypertension without targetorgan lesions were identified, while hyperandrogenism was associated with 17,6% of cases. Arterial hypertension associated with hyperandrogenism was characterized by a rise in blood pressure in the early morning hours. Estradiol levels, while remaining within normal limits, were statistically significantly lower in patients with arterial hypertension compared with men with elevated testosterone but without hypertension. CONCLUSION: No cases of arterial hypertension were observed in «physiological¼ hyperandrogenism due to elevated DHT levels, whereas its incidence in «physiological¼ hyperandrogenism due to elevated total testosterone was 23,5%. The features of steroidogenesis were increased production of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione in men with testosterone hyperandrogenism and decreased estradiol production in patients with arterial hypertension compared with patients without testosterone hyperandrogenism.

[Adipokines and the cardiorespiratory system in young patients with type 1 diabetes mellitus].

Early screening of complications of diabetes mellitus (DM) is one of the priorities for public health. Most patients with type 1 diabetes mellitus (T1DM) are patients of working age. New strategies for the primary prevention of cardiovascular disease (CVD) are needed to prevent their early disability. AIM: To assess the predictive value of adipokines in relation to a personalized approach to the need for an in-depth examination of young patients with T1DM. MATERIALS AND METHODS: The study included 98 patients without CVD: 70 patients with T1DM (mean age 26.4±8.1 years) and 28 patients without DM (mean age 27±9 years). All patients underwent a general clinical examination, the levels of adipokines were determined, ergospirometry, echocardiography, and bioimpedancemetry were performed. RESULTS: Changes in the cardiorespiratory system in patients with T1DM were revealed, in comparison with persons without T1DM: anaerobic threshold was reached faster (p=0.001), maximum oxygen consumption was lower (p=0.048), metabolic equivalent was reduced (p=0.0001). Signs of myocardial remodeling were found in the T1DM group: there was an increase in the relative wall thickness (p=0.001), the posterior wall of the left ventricle (p=0.001), myocardial mass index (p=0.049), in comparison with persons without T1DM. Changes in the adipokines system were revealed: higher levels of resistin (p=0.002) and visfatin (p=0.001), lower level of adiponectin (p=0.040) in T1DM. A positive correlation was found between posterior wall of the left ventricle and visfatin (p=0.014) and a negative relationship between adiponectin and relative wall thickness (p=0.018) in T1DM. CONCLUSION: In T1DM, even at a young age, there are multifactorial changes in the heart, which can be detected even at the preclinical stage. The data obtained can be used to identify groups of patients at high risk of developing dangerous CVD in T1DM, which can form the basis for determining the timing of the start of preventive therapy.

[MiRNAs in the diagnosis of cardiovascular diseases associated with type 2 diabetes mellitus and obesity]. / MikroRNK v diagnostike serdechno-sosudistykh zabolevanii, assotsiirovannykh s sakharnym diabetom 2-go tipa i ozhireniem.

Worldwide, the number of patients with type 2 diabetes mellitus (T2DM), obesity, and cardiovascular diseases (CVD) continues to increase steadily. Despite long-term studies of obesity and concomitant diseases, the molecular genetic bases for the development of these pathological conditions have remained the subject of numerous investigations so far. Recent investigations point to the involvement of miRNAs as dynamic modifiers of the pathogenesis of various pathological conditions, including obesity, T2DM, and CVD. MicroRNAs are involved in various biological processes underlying the development of CVDs, including endothelial dysfunction, cell adhesion, and atherosclerotic plaque formation and rupture. Some of them are considered as potential sensitive diagnostic markers of coronary heart disease and acute myocardial infarction. Approximately 1,000 microRNAs are found in the human body. It has been determined that miRNAs regulate 30% of all human genes. Among them there are about 50 circulating miRNAs presumably associated with cardiovascular diseases. This review provides recent data on the participation of some miRNAs in various pathological and physiological states associated with CVD in DM and obesity. An extended and exact understanding of the function of miRNAs in the gene regulatory networks associated with cardiovascular risk in obesity will be able to reveal new mechanisms for the progression of disease, to predict its development, and to elaborate innovative therapeutic strategies.

[Antithrombotic therapy after X-ray endovascular treatment: are there specific features in patients with diabetes mellitus?].

According to the current guidelines for the intervention treatment of patients with coronary heart disease, the primary and secondary prevention of cardiovascular events is long-termpharmacotherapy with platelet function inhibitors. Although undeniable progress has been made in the use of this group of medicaments, there are, however, issues calling for further investigation in the population of diabetic patients in particular. Along with the general principles of thrombosis, there are mechanisms that cause additional platelet hyperactivity in the presence of insulin deficiency and insulin resistance, metabolic and cellular disorders induced by hyperglycemia. The risk of resistance to standard antithrombotic therapy suggests a search for alternative ways to inhibit platelet aggregation, which is particularly relevant in diabetic patients.

[Multidirectional effects of exercise of various type and intensity on lipid transport system of blood in healthy subjects and patients with coronary heart disease].

AIM: To evaluate effects of dynamic exercise (DE) and static leg exercise (SE) varying by intensity on blood serum spectrum of lipoproteins and apolipoproteins in healthy persons and patients with coronary heart disease (CHD). MATERIAL AND METHODS: Healthy 12 men and 12 CHD patients of functional class I performed bicycle DE of maximal (for age) intensity (100%), submaximal (80, 70 and 60%), SE of maximal and submaximal intensity. Blood samples were taken before the exercise, after it and 3 hours after the exercise. RESULTS: DE of high intensity (80% and higher) and SE of maximal and moderate intensity (100 and 60%, respectively) produced atherogenic changes in the blood of both healthy subjects and CHD patients: a rise in total cholesterol, LDLP cholesterol, triglycerides, apolipoprotein (apo) B and apo B/ apo AI. Moderate (60%) DE gave rise to antiatherogenic changes in the blood: a fall in lipoproteins containing apoB and a rise in concentration of apo AI both in healthy and CHD subjects. CONCLUSION: To prevent atherosclerosis by correction of atherogenic lipid disorders, CHD patients and healthy persons should do DE of moderate intensity in addition to other prophylactic measures.

[Physical exercise and atherosclerosis: dynamic high intensity exercise as a factor inducing exogenous dyslipidemia]. / Fizicheskie nagruzki i ateroskleroz: dinamicheskie fizicheskie nagruzki vysokoi intensivnosti kak faktor, indutsiruiushchii ékzogennuiu dislipidemiiu.

Effect of dynamic exercise of various intensity (maximal 100% and submaximal -- 80, 70 and 60% of individual maximally tolerated work load) on blood lipids, lipo- and apolipoproteins (apo) was studied in healthy subjects and patients with coronary heart disease. Both in healthy persons and patients high intensity (100 and 80%) exercise was associated with atherogenic changes of lipid transport system: increases of levels of total and low density lipoprotein cholesterol, triglycerides, apolipoprotein B and apo B/apo-A1 ratio. On the contrary, changes after exercise of moderate (60%) intensity (lowering of apo-B containing lipoproteins in healthy subjects and patients and elevation of apo-A1 concentration in healthy subjects) were antiatherogenic.

[Physical exercise and atherosclerosis: proatherogenic effects of high and moderate intensity static exercise on blood lipid transport system]. / Fizicheskie nagruzki i ateroskleroz: proaterogennoe vliianie staticheskikh nagruzok vysokoi i umerennoi intensivnosti na lipidtransportnuiu sistemu krovi.

Effects of high (100 and 80 kg) and moderate (60 kg) intensity static leg exercise on blood serum lipoproteins and apolipoproteins (apo) A1 and B were studied in healthy subjects (n=11) and patients with coronary heart disease and class I angina (n=11). Static leg exercise with loads exceeding 60 kg were associated with atherogenic changes of blood lipid transport system: elevation of levels of triglycerides, apoprotein B and apo B/A ratio both in healthy subjects and patients, and of total and low density lipoprotein cholesterol in patients. These post exercise changes were more pronounced in the presence of fasting hyperlipidemia and their severity increased with increase in duration of exercise. Static leg exercise did not increase concentration of high density lipoprotein cholesterol. For prevention of post exercise atherogenic dyslipidemia it is expedient to supplement strength training programs with dynamic exercise of moderate intensity.