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Obesity is a chronic disease, heterogeneous in etiology and clinical manifestations, progressing with a natural course, characterized by excessive deposition of fat mass in the body. This pathological condition has taken on the scale of a global epidemic in recent years, which continues to progress steadily, currently affecting more than 2 billion people worldwide. Due to its heterogeneity, obesity has a negative impact on the work of almost all organs and systems of the body, contributing to the emergence of new concomitant diseases and pathological conditions that significantly worsen the quality of life of these patients. Thus, a close relationship between type 2 diabetes mellitus and cognitive impairment has long been known, as well as with a number of other somatic diseases: coronary heart disease, atherosclerosis, non-alcoholic fatty liver disease, dyslipidemia, malignant neoplasms and other associated pathological conditions against the background of overweight and obesity.Currently, the problem of the relationship of cognitive impairment in patients with overweight or changes in the glycemic profile is very relevant, due to the high prevalence and insufficient study of this issue.

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Background: Chronic brain dyscirculation is one of the frequent type 2 diabetes mellitus (DM) complications and leads to patients' disability. Sodium-glucose co-transporter type 2 inhibitors (SGLT-2i) have been proven to have advantages for cardiovascular system, but their effect on the central nervous system (CNS) has not been studied enough., Aim: To study empagliflozin effect on CNS damage functional and laboratory parameters in patients with type 2 DM and, under experimental conditions, to investigate the mechanisms of the drug neurotropic effect., Materials and Methods: The clinical part of the study included patients with type 2 DM on metformin monotherapy (n=39). Patients with a target glycated hemoglobin level formed the "MET" group (n=19), in patients with a non-target glycated hemoglobin level empagliflozin was co-administered for the following 6 months (the "MET+EMPA" group, n=20). Healthy volunteers comprised the control group (n=16). The cognitive status and neuron-specific enolase (NSE) and neurofilament light chains (NLC) concentration were studied. DM was modeled in rats, thereafter the rats were treated with empagliflozin for 8 weeks. Microglia activation was assessed using anti-Iba-1 antibodies and morphological changes in neurons when stained by the Nissl method., Results: Both in the "MET+EMPA" and the "MET" groups cognitive deficits were observed, according to the Montreal Cognitive Assessment (MOCA) (24.0 (23.0; 27.0) and 25.0 (21.0; 27.0) points) and the Mini-Mental State Examination (MMSE) (23.75 (23.0; 27.0) and 25.0 (21.0; 27.0) points). Empagliflozin therapy led to the cognitive status normalization after 6 months (26.5 (24.0; 27.0) points according to the MOCA scale and 27.5 (24.0; 28.0) points according to the MMSE). Initially, all patients had a significant increase of NSE (3.60 (2.66; 3.76) ng/ml in the "MET" group, 3.22 (2.94; 3.54) ng/ml in the "MET+EMPA» group, 2.72 (2.13; 2.72) ng/ml in the «Control» group) and NLC (4.50 (3.31; 5.56) ng/ml in the «MET» group, 5, 25 (3.75; 6.25) ng/ml in the «MET+EMPA» group comparing with 3.50 (2.25; 3.50) ng/ml in the «Control» group). Empagliflozin therapy led to a significant decrease in NLC already after 3 months (3.80 (3.25; 3.87) ng/ml), without significant influence on the NSE level. In the experiment, DM was characterized by an increased number of activated microgliocytes and destructured neurons and a decreased number of neurons with a normal structure. Empagliflozin therapy was accompanied by a decrease in the number of immunopositive microgliocytes in the CA1 zone of the hippocampus and an increase in the number of structured neurons., Conclusion: Type 2 diabetes mellitus is characterized by functional and biochemical changes in the central nervous system even under satisfactory glycemic control. Therapy with empagliflozin has a neuroprotective effect, manifested in an improvement in cognitive status and a decrease in NLC level. Empagliflozin reduces neuronal damage and abnormal microglial activation.

Background: Patients with diabetes mellitus (DM) are at risk for a higher incidence and severity of COVID-19, as well as its adverse outcomes, including post-Covid syndrome., Aim: to assess the incidence of cardiorenal complications in patients with type 1 and type 2 diabetes (T1DM/T2DM) who have had COVID-19, and to analyze the structure and severity of disorders according to examination data at the Diamobil mobile medical diagnostic and treatment center., Materials and Methods: a cohort of T1DM and T2DM patients examined in Diamobil (n=318), with a confirmed anamnesis of COVID-19 (n=236). The time interval between COVID-19 and the visit to Diamobil was 8.7/8.2 months for T1DM/T2DM. The parameters of the last visit before COVID-19 recorded in the Federal Register of Diabetes (FRD) were used as initial data., Results: Clinical characteristics of patients with T1DM/T2DM: age - 49.2/64.5 years, duration of DM - 22/11 years, proportion of women - 64/73%, respectively. After analysis the data from visits before and after COVID-19 there weren't statistically significant differences in HbA1c levels for both types of DM (before 9.0/8.3%; after 8.4/8.2%, respectively), there was the intensification of glucose lowering therapy (the proportion of patients with T2DM on 2 and 3 component therapy increased by 4.3% and 1.6%, the proportion of patients on insulin therapy by 16%). After COVID-19, there was a statistically significant decrease in glomerular filtration rate (GFR) in T1DM from 88.1 to 62 ml/min/1.73 m2; with T2DM from 74.7 to 54.1 ml/min/1.73 m2. When assessing acute diabetic complications, there was an increase in the frequency of coma in T1DM by 1.5 times, severe hypoglycemia in T1DM by 3 times, and in T2DM by 1.7 times. Analysis of the frequency of cardiorenal complications before and after COVID-19 showed a total increase of 8.5% in T1DM, by 13.2% in T2DM, of which myocardial infarction, ischemic heart disease, and CHF increased in T1DM in the range from 1.5 to 5 times, with T2DM by 1.3 times, the frequency of CKD with T1DM by 1.5 times, with T2DM by 5.6 times., Conclusion: There was a decline of kidney filtration function (decrease in GFR) and an increase in the frequency of cardiovascular complications in both types of diabetes in post-Covid period while patients achieved a stable HbA1c levels by intensifying therapy during the COVID-19 infection. This fact reflects combined damage to the kidney and cardiovascular system as a part of the post-Covid syndrome and determines a key set of measures for the development of preventive strategies.

Aim: To study the impact of type 2 diabetes mellitus (DM2) on the severity of liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD)., Materials and Methods: To conduct a paired case-control study 2989 patients were examined at the Federal Research Center of Nutrition, Biotechnology and Food Safety. Pairs were matched by gender and age and distributed into groups: NAFLD + DM2+ ( n =313), NAFLD + DM2- (n=313) and a control group of patients without NAFLD and without DM2 ( n =313). The severity of liver steatosis was determined by measuring the controlled attenuation parameter. The severity of liver fibrosis was determined by measuring the liver stiffness measurement. Body composition of the patients was determined using bioimpedance measurements. Indicators of lipid and carbohydrate metabolism, and the serum activity of liver enzymes was determined by standard biochemical methods., Results: In NAFLD + DM2+ group compared to NAFLD + DM2- group, and in NAFLDM + DM2-compared to the control group, weight, BMI, waist and hip circumference, waist-to-hip ratio were higher, while in all. In NAFLD + DM2+ and NAFLD + DM2- groups the volume of fat mass directly correlated with the level of blood triglycerides ( r =0.21), HbA 1 с ( r =0.32) and fasting blood glucose ( r =0.35), and inversely correlated with high-density lipoproteins ( r =-0.19). In NAFLD + DM2+ group versus NAFLD + DM2- group severe steatosis (S3, 78% versus 59.4%; p< 0.001) and severe fibrosis (F4, 8% vs 2.6%; p< 0.001) was more common; 70% of patients in the NAFLD + DM2- group had no liver fibrosis according to elastography (F0), while in the NAFLD + DM2+ group only 43.2% of patients had no liver fibrosis ( p< 0.0001)., Conclusion: When NAFLD is accompanied by DM2, there is an increase in total fat mass, the severity of steatosis and liver fibrosis, and an associated deterioration of lipid metabolism. More than half of these patients have various stages of liver fibrosis, which indicates the progressive nature of the disease.

Aim: To evaluate the efficacy and safety of azilsartan medoxomil for preoperative preparation and improving the long-term prognosis of elective percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD), arterial hypertension (AH), and type 2 diabetes mellitus (DM)., Material and Methods: The study sample included patients with type 2 DM referred for elective PCI who had poor blood pressure (BP) control according to 24-hour BP monitoring (24-BPM) (mean daily systolic BP ≥130 mmHg, mean daily diastolic BP ≥80 mmHg). The data were collected from 2018 through 2020. A total of 75 patients was included and distributed by simple randomization into two groups: group 1 (main, n=37) received azilsartan medoxomil as an antihypertensive drug at a dose of 40 mg/day (previously prescribed angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ARB) were discontinued); group 2 (control, n=38) continued on their previous antihypertensive therapy. The follow-up period was 6 months. During each of 5 consecutive follow-up visits, the patient was examined, 24-BPM was recorded, and urinary markers of renal dysfunction (glomerular filtration rate, GFR; neutrophil gelatinase-associated lipocalin, NGAL; urine albumin-creatinine ratio, UACR; kidney injury molecule, KIM-1; and interleukin-18, IL-18) were measured., Results: During the azilsartan treatment, GFR decreased by 7.4%, while in the control group, it decreased by 18.9% (p&lt;0.001). For 6 months of follow-up, no changes in the NGAL concentration were found in the main group, while the NGAL concentration in the control group increased by 12.9%. With azilsartan, there was a decrease in the urinary concentration of IL-18 (16.9%), while in patients of the control group, IL-18 increased (7.14%). Proteinuria progressed in both groups, which was expectable given the presence of DM; however, in patients receiving azilsartan, the UACR value increased by 37.5%, while in patients of the control group, it increased by 96.15%. These differences were statistically significant. No statistically significant differences were found in the concentrations of cystatin C and KIM-1., Conclusion: This study demonstrated two important facts: the possibility for diagnosing contrast-induced acute kidney injury (CI-AKI) using new, more sensitive markers of kidney damage, which is important for assessing the effectiveness of prevention, and the possibility of using ARBs, in particular azilsartan, for the prevention of CI-AKI in patients with IHD in combination with AH and DM.

Aim: To compare the frequency of cardiovascular events (CVE), to assess the risk of cardiovascular death using the mSCORE and the development of type 2 diabetes mellitus (DM) using the FINDRISC in patients with rheumatoid arthritis (RA) with and without hypothyroidism., Materials and Methods: The study included 149 patients (125 women, 24 men) with RA (median age - 57 [52; 61] years). In all patients, traditional factors of cardiovascular risk and glucose metabolism disorders (age, smoking status, total blood cholesterol, blood pressure, overweight, abdominal obesity - AO, heredity burdened by diabetes, insufficient physical activity, the lack of the necessary amount of berries, fruits and vegetables in the daily diet, history of hyperglycemia episodes), the 10-year risk of death from cardiovascular causes according to the mSCORE and the risk of developing type 2 DM according to the FINDRISС were assessed, a history of CVE (myocardial infarctions, and its revascularization, stroke) was recorded., Results: Hypothyroidism was diagnosed in 17.4% of RA patients. Patients with hypothyroidism (group 1) were more likely to have AO and less likely to consume unsufficient dietary fiber than patients with euthyroidism (group 2). Moderate, high and very high risk of development according to the mSCORE and FINDRISC was detected in 61.5% of hypothyroid patients and 48.8% euthyroid patients, according to mSCORE alone - in 30.8 and 44.7%, according to FINDRISC - in 0 and 2.4%, respectively (p>0.05 in all cases); 11.5% of patients in group 1 and 6.5% in group 2 suffered from CVE (OR 1.875, 95% CI 0.462-7.607; p =0.63)., Conclusion: It is necessary to evaluate the thyroid gland function, especially in patients with AO due to the high frequency of hypothyroidism in RA. Hypothyroidism did not have an independent effect on the severe CVЕ rates, as well as risk assessment according to the score and FINDRISC in RA patients. Theses, with and without hypothyroidism, were predominantly in the moderate, high, very high risk groups according to both scales.

Aim: To analyze the results of screening of the population older than 40 years for early detection of risk factors for cardiovascular diseases in real clinical practice of family clinics in the Aral Sea region., Material and Methods: The results of screening of the population older than 40 years were analyzed for a total of 2,430 respondents from family clinics of the district (Republic of Uzbekistan, Republic of Karakalpakstan, Ellikkala district) according to the modified WHO PEN protocol. 1,020 of the respondents with blood pressure ≥140/90 mm Hg were included in the study (mean age, 57.68±8.06 years; women, 61.4%; men, 38.6%). Additionally, the following parameters were determined: salt-taste threshold using the R. Henkin method, echocardiography, ultrasonography of the brachiocephalic arteries, blood lipid spectrum, microalbuminuria, serum creatinine and uric acid. Statistical data are presented as mean±SD. The prevalence of signs in the study group was assessed using the Pearson's chi-square test, and the Pearson correlation coefficient was used., Results: Among the patients with elevated blood pressure included in the study, 24 (2.4%) were younger than 40 years, 847 (81%) were 40-65 years old, and 169 (16.6%) were older than 65 years. Low cardiovascular risk was twice more common among women compared to men: 11.3% vs. 5.6% (χ²=8.990; p=0.003); almost 75% fewer patients with ischemic heart disease, 7.4% vs. 28.9% (χ²=14.939; p=0.0001); however, the incidence of type 2 diabetes mellitus was twice higher, 13.7% vs. 7.4% (χ²=9.205; p=0.002); the female group had significantly fewer cases of postinfarction cardiosclerosis (PICS) (χ²=5.313; p=0.021). Among women, there were no tobacco users or regular alcohol drinkers whereas among men these risk factors were identified in 59.4% (χ²=178.848; p=0.0001) and 35% (χ²=82.238; p=0.0001), respectively. 85.6% of the respondents had a high salt-taste threshold, 96% had left ventricular hypertrophy, 76% had microalbuminuria, 21% had proteinuria, and 92% of both men and women had a common carotid artery intima-media thickening &gt;0.9 mm., Conclusion: The study showed a broad prevalence of cardiovascular risk factors in the population of hypertensive patients in the Aral region, a high salt-taste threshold, and significant damages to target organs, which differed from other regions of Uzbekistan. Among hypertensive men, there was a significant prevalence of tobacco and alcohol use, and a significantly more frequent detection of ischemic heart disease, PICS and hyperuricemia compared to women; in the female population, the prevalence of type 2 diabetes mellitus was significantly greater.

In a number of clinical studies, Recognan (citicoline) has demonstrated its effectiveness in patients with ischemic stroke, traumatic brain injury, cognitive disorders of various origins, in the complex therapy of asthenic and anxiety-depressive disorders, showing neuroprotective and neuropreparative properties. In recent years, emphasis has been placed on citicoline appointment in the complex therapy of patients with type 2 diabetes mellitus (DM2). In experimental (induced DM2) and clinical studies of patients with cerebrovascular diseases (CVD) and DM2, the effectiveness of Recogan (citicoline) against diabetic retinopathy and diabetic polyneuropathy in more significant clinical changes and negative dynamics absence of important laboratory parameters (blood glucose levels) in acute and stroke recovery periods in patients with DM2. The analysis of research materials allows Recogan to recommend to patients with CVD and DM2.

Non-alcoholic fatty liver disease (NAFLD) is considered to be metabolically determined and alimentary condition, one of the components of metabolic syndrome. Therefore, dietary patterns of patients with different clinical types of the disease are worth to be studied . The aim of the research was to study the dietary patterns in patients with NAFLD and with type 2 diabetes mellitus (T2DM) (group T2DM+) compared to the control group without T2DM (T2DM-). Material and methods . A retrospective analysis of the database (n=316) of patients with NA FLD, formed in the period from 202 1 to 2023, was carried out. A total of 79 sex- and agem atched pairs of T2D+ and T2D- pat ients were selected for the case-control study. Hepatic steatosis and fibrosis stage assessment was performed using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). Actual nutrition was evaluated using a semi-quantitative method of assessing consumption frequency during a personal interview. Consumption of 100 grouped food items was assessed. Blood parameters characterizing lipid and carbohydrate metabolism were assessed. Results . Among patients with T2DM+, patients with NASH (24.1 vs 8.9%, p=0.005) and patients with severe liver fibrosis F3-F4 (32.9 vs 10.1%, p<0.0001) were significantly more common. There were no differences between the T2DM+ and T2DM- groups in energy consumption (1969 [1492; 3098] vs 1870 [1380; 2593] kcal/day; p=0.4), proteins (90.5 [71.5; 130.3] vs 81.0 [59.4; 116.0] g/day; p=0.1), fats (83.0 [66.7; 144.9] vs 78.8 [59.2; 116.4] g/day; p=0.3), carbohydrates (220 [156; 312] vs 209 [155; 282] g/day; p=0.9). The study of dietary patterns revealed greater consumption of meat and meat products (1.23 [0.84; 1.73] vs 0.96 [0.71; 1.37] times a day, p=0.03), fish and seafood (0.37 [0.17; 0.89] vs 0.27 [0.13; 0.51] times a day, p=0.01) in T2DM+ group. It was found that in patients with T2DM the intake of calories and the following nutrients from meat and meat products was more, then without: energy (289.6 [174.9; 420.3] vs 191.9 [148.2; 336.5] kcal/day, p=0.006), proteins (25.8 [17.2; 36.5] vs 18.6 [12.6; 29.6] g/day, p=0.008) and fats (18.9 [10.8; 31.4] g/day vs 13.7 [10.3; 23.6] g/day, p=0.01). Similar data was obtained for fish and seafood, with energy (59.7 [28.3; 117.3] vs 45.2 [20.5; 70.1] kcal/day, p=0.03), proteins (8.1 [6.9; 16.8] vs 6.3 [6.7; 10.2] g/day, p=0.02) and fats (3.0 [1.5; 6.4] vs 1.9 [0.9; 3.8] g/day, p=0.01) consumed more in T2DM+ group. Conclusion . In the traditional analysis of actual nutrition in NAFLD patients with and without T2DM, no significant differences were found. However, the structure of the patients' diet differs significantly due to meat and meat products, fish and seafood. The identified differences may indicate the need to change dietary recommendations for patients with T2DM, and may also become the basis for the development of innovative food for special dietary uses aimed at improving the quality of nutrition of patients and, as a result, remission of the underlying disease., Competing Interests: The authors have no conflict of interest to declare., (Copyright© GEOTAR-Media Publishing Group.)

Early detection of diabetic retinopathy (DR) is an urgent ophthalmological problem in Russia and globally., Purpose: This study assesses the prevalence of asymptomatic retinopathy and attempts to identify risk groups for its development in patients with type 1 and 2 diabetes mellitus (T1DM and T2DM)., Material and Methods: The study involved clinics from 5 cities in the Russian Federation and it included 367 patients with DM, 34.88% men and 65.12% women, aged 50.88±20.55 years. 34.88% of patients suffered from T1DM, 65.12% suffered from T2DM, the average duration of the disease was 9.02±7.22 years. 58.31% of patients had a history of arterial hypertension, 13.08% had a history of smoking. The primary endpoint was the frequency of detection of diabetic changes in the eye fundus of patients with T1DM and T2DM in general; the secondary endpoint - same but separately, and for T2DM patients depending on the duration of the disease. The exploratory endpoint was the assessment of the influence of various factors on the development of DR. The patients underwent visometry (modified ETDRS table), biomicroscopy, mydriatic fundus photography according to the «2 fields» protocol., Results: The average detection rate of DR was 12.26%, primarily observed in patients with T2DM (13.81%), women (9.26%), in both eyes (8.17%). Among patients with DR, 26 (19.55%) had glycated hemoglobin (HbA1c) level exceeding 7.5% ( p =0.002), indicating a direct relationship between this indicator and the incidence of DR. Logistic regression analysis showed that the duration of diabetes of more than 10 years has a statistically significant effect on the development of DR. In the modified model for odds estimation, the likelihood of developing DR is increased by the duration of DM for more than 10 years; increased blood pressure; HbA1c level >7.5%., Conclusion: The obtained results, some of which will be presented in subsequent publications, highlight the effectiveness of using two-field mydriatic fundus photography as a screening for DR.

Almost 90% of patients with type 2 diabetes mellitus (DM2) are obese. Obesity increases the risk of developing DM2 several times. The calculation of anthropometric indices is used to diagnose the severity of obesity, as well as to assess the risk associated with obesity. The aim of the study is to study the relationship between Body Mass Index (BMI), waist circumference to hip circumference ratio (waist-to-hip ratio, WC/HR), Body Roundness Index (BRI) and Visceral Adiposity Index (VAI) with the risk of hypoglycemia in elderly and senile patients with DM2. The study included 122 elderly and senile patients (mean age 71±6,18 years) with DM2. The study participants were divided into 2 groups: patients with cases of hypoglycemia (n=65) and patients without a history of hypoglycemia (n=57). We have found that lower BMI, WC/HR, BRI, and VAI values are significantly associated with an increased risk of hypoglycemia in patients with DM2 of older age groups.

Type 2 diabetes mellitus is one of the most common non-infectious diseases in the world. Among people with type 2 diabetes, patients of the older age group. An in understanding of the early cardiovascular manifestations of diabetes occupies an important place in international research and prevention programs, given that cardiac vascular complications are the cause of death in patients with diabetes. Recent studies evaluating left ventricular diastolic dysfunction as a characteristic predictor of diabetic cardiomyopathy by echocardiography. In accordance with the recommendations for diastolic dysfunction, have shown that the algorithm of the informative algorithm is used to determine left ventricular diastolic dysfunction in patients with prognosis in predicting cardiovascular complications.

Mucormycosis is a disease caused by fungi of the Mucorales family, widespread in the environment, with pronounced angiotropism and the ability to angioinvasion, leading to thrombosis with surrounding necrosis. The main triggers for the development of mucormycosis are: immunodeficiency states, use of glucocorticosteroid drugs, decompensation of diabetes mellitus, concomitant diseases, age > 65 years. We present a clinical case of rhinocerebral mucormycosis in a 79-year-old patient against the background of uncontrolled type 2 diabetes mellitus with ketoacidosis, a condition after previous glucocorticosteroid therapy for COVID-19 (according to the severity of the disease). After suffering a new coronavirus infection caused by the SARS-CoV-2 virus, she was admitted to the hospital with complaints characteristic of mucormycosis. On the 5 th day of hospital stay, the patient's condition worsened significantly, despite the correction of the therapy, and on the 12 th day the patient died. According to the results of the autopsy, it was established that the rhinocerebral mucormycosis was complicated by thrombosis of the anterior and posterior left cerebral arteries with subsequent infarctions in the frontal lobe and parieto-occipital region of the brain left hemisphere, cerebral edema, which was the immediate cause of death.

With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic coma of the "pre-insulin era" to severe vascular complications in the modern period. The key risk factors for diabetic angiopathies in diabetes mellitus are poor glycemic control in combination with a long course of the disease. Over the past 30 years, there has been a downward trend in the incidence of late vascular complications of diabetes both worldwide and in Russia. In particular, the frequency of cardiovascular events (myocardial infarctions, strokes, amputations) decreased, and the incidence of several other complications, such as diabetic retinopathy and neuropathy, stabilized. However, the incidence of chronic kidney disease and chronic heart failure is still increasing. The Joslin Medal, awarded to patients over 50, 75 and even 80 years of life with diabetes, reflects success in the fight against this disease.

Aim    To study the incidence and effect of non-alcoholic fatty liver disease (NAFLD) on clinical outcomes in patients with decompensated chronic heart failure (DCHF).Material and methods    The study included 338 patients with NYHA functional class III-IV DCHF (51.2% men, mean age 72.8±11.7 years), arterial hypertension (AH) in 90%, myocardial infarction in 37%, atrial fibrillation in 64%, chronic kidney disease (CKD) in 42%, type 2 diabetes mellitus (T2DM) in 35%, left ventricular ejection fraction (LVEF) &lt;40% in 27%. NAFLD was diagnosed based on the 2021 Clinical Guidelines of the Russian Scientific Medical Society of Therapists and the Scientific Society of Gastroenterologists of Russia. The stage of liver steatosis was determined using transient elastometry with assessment of the controlled attenuation parameter (CAP) of ultrasound (S, dB/m) using a FibroScan device. Threshold CAP values &lt;294 dB/m corresponded to the degree of steatosis: S0; S1, 295-309 dB/m; S2, 310-330 dB/m; S3, ≥331 dB/m.Results    NAFLD was diagnosed in 28.9% of patients. The patients were divided into two groups: group 1 included patients with CHF and NAFLD (n=98 (28.9%), 50.0% men) and group 2 included patients with CHF without NAFLD (n=240 (71.0 %), 51.6% men). A multivariate regression analysis showed that independent predictors of NAFLD were systolic blood pressure ≥130 mm Hg (odds ratio (OR), 3.700; p &lt;0.001), history of T2DM (OR, 2.807; p &lt;0.005), and waist circumference &gt;111 cm (OR, 2.530; p &lt;0.012). Patients with CAP ≥331 dB/m (S3) had a worse prognosis during the 2-year follow-up for the composite adverse outcome (all-cause mortality + readmission) (Kaplan-Meier curves - Log-Rank p=0.035).Conclusions    NAFLD was detected in almost one-third of patients hospitalized for DCHF. AH, T2DM, and abdominal obesity were associated with a high risk of NAFLD. However, only severe steatosis (S3) was an independent predictor of adverse clinical outcomes during a 2-year period after adjustment for known risk factors.

Aim: To identify the features of the course of COVID-19 in patients with type 2 diabetes mellitus (T2DM), depending on the intake of hypoglycemic therapy at the prehospital stage, in conjunction with the functional state of the kidneys., Materials and Methods: A retrospective analysis of 291 case histories of patients with COVID-19 and T2DM hospitalized in the infection department of Semashko Regional Clinical Hospital from January to December 2021, including the main clinical and laboratory parameters. Results. Among hospitalized patients with COVID-19, patients with T2DM had a higher mortality rate. An analysis of the case histories of deceased patients with COVID-19 and T2DM showed that at admission, body mass index (BMI), C-reactive protein, and creatinine were higher than those of survivors and amounted to BMI - 33 [30; 39] and 33 [28; 36] kg/m3; p=0.039, C-reactive protein - 77 [47.5; 106.0] and 57 [27.0; 89.0] mg/l; p=0.015, in terms of creatinine level - 89 [70.0; 144.0] and 82 [66.0; 101.0] µmol/l; p=0.039, respectively. It was found that in the second week of hospitalization in the group of deceased patients with COVID-19 and T2DM, the creatinine level was statistically significantly higher than in surviving patients and amounted to 94.5 [71.5; 141.0] and 72.5 [57.0; 88.0] µmol/L; p<0.001, respectively. The probability of death in hospitalized patients with type 2 COVID-19 and T2DM depended on BMI and creatinine levels at the second week of hospitalization. Patients with prehospital correction of hyperglycemia dipeptidyl peptidase-4 inhibitors (iDPP-4)/ glucagon-like peptide-1 receptor agonists (agGLP-1)/ sodium-glucose co-transporter 2 inhibitors (iSGLT-2) had significantly lower creatinine levels at week 2 of hospitalization., Conclusion: In patients with moderate to severe COVID-19 with concomitant T2DM, special attention should be paid to the combination of high BMI and creatinine in the second week of hospitalization, which is a prognostically unfavorable predictor of death in such patients.

Against the background of the rapid increase in the prevalence of obesity worldwide, the frequency of the development of metabolic disorders associated with it is increasing. Non-alcoholic fatty liver disease (NAFLD) is recognized as the main hepatic manifestation of metabolic syndrome. Currently, NAFLD affects about 25-30% of the world's population and, in most cases, is associated with obesity and type 2 diabetes, as well as with increased cardiovascular risk. Diagnosis of NAFLD includes laboratory and instrumental research methods, various non-invasive tests, and the "gold standard" for confirming the diagnosis is a liver biopsy. Due to the greater availability and sufficient information content, ultrasound methods of research come to the fore in the examination of patients at risk. Lifestyle modification remains the cornerstone in the management of such patients, however, given the complex pathogenesis of the disease, treatment of NAFLD may include several therapeutic strategies. In the treatment of comorbid patients, some groups of hypoglycemic drugs are used, including ar-GLP-1, i-NGL-2, pioglitazone, lipid-lowering drugs, drugs for the treatment of obesity. The so-called hepatoprotectors, including essential phospholipids (EFL), have demonstrated their effectiveness in reducing liver damage due to antioxidant, antifibrotic, and lipid-regulating effects. According to a number of studies, EFL helps to reduce the severity of steatosis, improving both objective and subjective manifestations of hepatic dysfunction. In this connection, the guidelines of various countries include EFL group drugs in the protocol of treatment of patients with NAFLD both in monotherapy and in combination with other drugs.

Polycystic ovary syndrome (PCOS) is one of the most pressing problems in endocrine gynecology. The main signs of the disease are hyperandrogenism, menstrual and/or ovulatory dysfunction, and polycystic ovarian structure according to ultrasound. Women with PCOS are at risk for developing metabolic syndrome, type 2 diabetes, cardiovascular disease, and endometrial cancer. In this connection, the pathogenetic mechanisms of the occurrence of this syndrome are continuously studied and new methods of treatment are being sought. PCOS is characterized by a wide range of various disorders of the neuroendocrine regulation of the reproductive system. The main focus of the review is aimed at summarizing information about the etiological role of neuropeptides and neurotransmitters, such as phoenixin, galanins, orexins, GABA, in the pathophysiology of PCOS and about the possibility of their use for diagnostic and therapeutic purposes. In recent decades, the interest of scientists has been focused on the study of KNDy neurons, because it is the kisspeptin synthesized by them that is one of the main regulators of the hypothalamic-pituitary-ovarian axis. This article discusses data on the significance of KNDy neurons in the pathogenesis of the syndrome. Information is provided on the effect of elevated levels of androgens and anti-Müllerian hormone on GnRH neurons. Also analyzed are studies on functional and structural disorders in the hypothalamus in PCOS. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1998.

Background: Diabetes mellitus (T2DM) is a serious medical and social problem. Now they are studying the possibility of a new stratification of diabetes. The possibility of cluster analysis for different durations of diabetes, in different cohorts to identify phenotypic clusters of T2DM and validation by reproducing clusters is relevant., Aim: Identify clusters of type 2 diabetes mellitus in patients with different disease duration based on five variables: HbA1c, age at diagnosis, BMI, HOMA-IR, HOMA-B and study the clinical features and complication rates in each cluster in the Novosibirsk region., Materials and Methods: Cluster analysis of K-means was performed in 2131 patients with T2DM, aged 44 to 70 years, with a duration of diabetes of 6.42±5.66 years, living in the Novosibirsk region based on 5 variables - HbA1c, age at -diagnosis, BMI, HOMA-IR, HOMA-B. All patients a complete clinical and laboratory examination. The insulin resistance index in the HOMA (HOMA-IR, u) and the β-cell function assessment index (HOMA-B) were calculated using the calculator -version 2.2.3 at www.dtu.ox.ac.uk., Results: Cluster analysis revealed: Cluster 1 included 455 patients with preserved β-cell function (HOMA-B 82.97±23.28%), moderate insulin resistance (HOMA-IR 5.57±4.72) and higher diastolic BP; Cluster 2 in 1658 patients with reduced function of β-cells (HOMA-B 21.71±12.51%), the lowest indices of insulin resistance (HOMA-IR 3.50±2.48) and was characterized by a longer duration of diabetes, high fasting glycemia , HbA1c, higher eGFR and MAU, men compared with women had a 31% higher risk of developing diabetic neuropathy and 28% more diabetic nephropathy; Cluster 3 in 18 patients with high function of β-cells (HOMA-B 228.53±63.32%), severe insulin resistance (HOMA-IR 6.92±4.77), features were high incidence of men, shorter duration of diabetes, lower fasting glycemia and HbA1c, lower diastolic BP and eGFR, high incidence of early development of diabetic retinopathy after 4.00±3.6 years., Conclusion: Cluster analysis in patients with different durations of diabetes mellitus confirmed the possibility of using cluster analysis to identify T2DM phenotypes in the Russian population. The clusters differed in the clinical characteristics of patients, the frequency and risk of diabetic complications. These results have potential value for early stratification of therapy.

Aim: To evaluate the effect of pleiotropic (anti-inflammatory and antifibrotic) effects of a lipophilic statin (atorvastatin) in the treatment of heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF)Material and methods. This observational study included 80 patients with HFpEF; 40 of them received atorvastatin 20-80 mg/day in addition to a standard treatment. 40 patient who refused of the statin treatment or had intolerance of the drug received only the standard treatment. The follow-up period was 12 months and included 5 visits. At the visits, the general condition of patients was evaluated; electrocardiography and echocardiography were performed at rest and during dosed physical exercise (PE); anthropometry was analyzed; and office blood pressure (BP), heart rate (HR) and parameters of systolic and diastolic LV function were recorded., Results: Among the patients included into the study, women aged 60-70 years prevailed who had pronounced obesity (n=46; 57.5% with class II-II obesity), severe arterial hypertension (AH) (n=65; 81.2% with grade 3 hypertension), dyslipidemia, type 2 diabetes mellitus, and chronic kidney disease. The administration of atorvastatin in addition to standard therapy was associated with regression of HF symptoms and increased PE tolerance; these effects were more pronounced after 6 months of observation. Furthermore, during a 12-month follow-up, significant multidirectional changes in LV global longitudinal strain were noted; in the main group, the LV global longitudinal strain increased indicating an improvement in the LV systolic function while in the control group, it decreased reflecting early, preclinical manifestations of HF progression. A diastolic stress test in combination with a cardiopulmonary stress test was performed in 64 patients with HFpEF at enrollment and at 6 and 12 months of follow-up. When the load reached 50 W in the atorvastatin treatment group after 12 months, a significant increase in tissue Doppler velocity parameters was revealed, specifically in e' septal and e' lateral. This led to a significant decrease in the E / e' ratio while in the control group, no time-related changes in these parameters were noted. Similar changes were also detected at higher levels of PE., Conclusion: Long-term use of the lipophilic statin (atorvastatin) in addition to a standard therapy was associated with regression of clinical manifestations of HFpEF, provided preservation of the systolic function, and some improvement in the LV diastolic function both at rest and during dosed PE.

A review of publications devoted to the analysis of genetic polymorphisms and features of the functioning of genes that affect the pharmacokinetics and pharmacodynamics of sodium-glucose cotransporter-2 inhibitors (SGLT2i) is presented. Objective of the study was to reveal information about genes whose polymorphism may affect the effectiveness of SGLT2i. The review was carried out in accordance with the PRISMA 2020 recommendations, the search for publications was carried out in the PubMed databases (including Medline), Web of Science, as well as Russian scientific electronic libraries eLIBRARY.RU from 1993 to 2022. Polymorphisms in the structure of several genes ( SLC5A2 , UGT1A9 , ABCB1 , PNPLA3 ) have been described that may affect the treatment of type 2 diabetes mellitus complicated by diseases such as chronic heart failure, chronic kidney disease, or non-alcoholic fatty liver disease. The information found on the genetic features of the development of the effects of SGLT2i is limited to a description of the differences in their pharmacokinetics. The relevance of currently available pharmacogenetic studies is largely constrained by small sample sizes.

Background: The problem of recurrent urinary tract infections (UTI) in patients with type 2 diabetes mellitus (DM 2) is relevant, especially when there is a combination of predisposing factors, such as female gender, history of UTI episodes, and therapy with sodium glucose cotransporter type 2 (SGLT-2) inhibitors, and the choice of effective and safe means could cause some difficulties, including ina terms of the burden of antibiotic resistance., Aim: To evaluate the effectiveness and safety of the phytoproduct Canephron ® N for the prevention of exacerbations of recurrent cystitis and the effect on metabolic parameters in patients with type 2 diabetes taking SGLT-2 inhibitors., Materials and Methods: Prospective, randomized, open, parallel group study in 60 women. The main group took the drug Canephron ® N for 3 months. The main parameters for evaluating were the frequency of recurrence of cystitis, level of albuminuria and LDL-cholesterol peroxidation product - malondialdehyde., Results: Within 3 months of taking Canephron ® N, exacerbations of chronic cystitis were diagnosed 2 times less often, a decrease in albuminuria was found in the form of an increase in the proportion of patients with an optimal level of albuminuria by 20%, a 50% reduction in the frequency of the initial increase in albuminuria, and the absence of moderate albuminuria in all patients at the end of course of therapy. A decrease in the level of MDA by 1.4 times was noted ( p= 0.019)., Conclusion: Thus, the herbal drug Canephron ® N can be used for accompanying therapy and prophylactic treatment in patients with recurrent cystitis on the background of DM 2, taking SGLT-2 inhibitors. The course of therapy should last at least 3 months.

Aim: To compare the efficiency of two surgical methods, holmium laser enucleation of prostate (HoLEP) and laparoscopic retropubic simple prostatectomy with clamping of internal iliac arteries and vesicourethral anastomosis [LPA+CIIA+VUA]) for treating of patients with benign prostatic hyperplasia (BPH) and type 2 diabetes mellitus (T2DM)., Materials and Methods: A total of 56 men with T2DM who underwent surgical treatment of BPH in the National Research Centre for Endocrinology of the Russian Ministry of Health (director - corresponding member of RAS Mokrysheva N.G..) in a period from 2021 until 2022 were included in the study. Patients with T2DM received two types of antidiabetic drugs: basal-bolus insulin therapy and metformin (1000 mg/day per os). Patients were divided into the group of LPA+CIIA+VUA (n=28) and HoLEP (n=28). Preoperative, intraoperative and postoperative examinations with an evaluation of intraoperative and early postoperative complications (I, II, III, IV grades according to the Clavien-Dindo scale) were performed. After 1 year of follow-up, International Prostatic Symptom Score (IPSS), "Quality of Life" score (QoL), International Index of Erectile Function-5 score (IIEF-5), maximal urine flow rate (Qmax), and postvoid residual volume (ml) were assessed. Efficiency of surgical procedures was estimated according to "trifecta": absence of postoperative complications, urine continence, maximal urine flow (Qmax) >15 ml/sec., Results: In the group of HoLEP, shorter postoperative bladder catheterization time but higher risk of urinary incontinence, bladder neck contracture and urethral strictures was found. LPA+CIIA+UVA leaded to a two-fold decrease in intraoperative hemoglobin loss with no necessity of repeat procedures., Conclusions: Our preliminary results demonstrated higher efficacy of LPA+CIIA+VUA for treatment of BPH in patients with T2DM than HoLEP. Patients who underwent LPA+CIIA+VUA were more often achieved the "trifecta". In order to implement LPA+CIIA+VUA into clinical practice, multi-center, large-scale, double-blind, placebo-controlled ("scar-surgery") randomized studies are required.

Aim: To evaluate the results of using Sildenafil in the form of an oral spray (Gent) for the treatment of erectile dysfunction (ED) in men with type 2 diabetes mellitus (DM) and prediabetes., Material and Methods: A total of 60 patients were divided into two groups of 30 people. The group 1 included patients with prediabetes, while group 2 consisted of patients with type 2 DM. All men had proven ED. The severity of ED was assessed using the International Index of Erectile Function (IIEF-5). To assess the state of penile blood flow, all patients underwent Doppler ultrasound before and after treatment. Patients with prediabetes used Sildenafil in the form of oral spray (Gent) 25 mg (2 doses) 1 time per day for 1 month, patients with type 2 diabetes received 50 mg (4 injections) every other day for 1 month. In addition, most of the subjects took metformin and followed diet therapy., Results: In patients of both groups, the administration of Sildenafil oral spray led to a decrease in body weight, waist circumference, a decrease in insulin and Hemoglobin A1C level without changing of hypoglycemic therapy in those with type 2 DM. In men with prediabetes, a decrease in fasting insulin levels was found. During treatment, half of the persons with impaired glucose metabolism had an increase in the testosterone level. According to IIEF-5, a decrease in the severity of ED in both groups of patients was seen. In men with prediabetes, the average IIEF-5 score increased from 15.98 to 21.57 points (p<0.05), while in patients with type 2 DM it improved from 12.18 to 18.44 points (p<0.05). Doppler ultrasound indicated a significant increase in the maximum systolic blood flow velocity and arterial resistivity index after treatment with Sildenafil oral spray in patients with both prediabetes and type 2 diabetes., Conclusion: Sildenafil oral spray can be effectively used for the treatment of ED in men with type 2 DM and prediabetes.

Aim    To study renal hemodynamics in patients with resistant arterial hypertension (RAH) in combination with type 2 diabetes mellitus (DM2) and to identify factors involved in the increase in intrarenal vascular resistance.Material and methods    This study included 59 patients (25 men) with RAH in combination with DM2. Mean age of patients was 60.3±7.9 years; 24-h blood pressure (24-BP) (systolic, diastolic, SBP/DBP) was 158.0±16.3 / 82.5±12.7 mm Hg during the treatment with 4.3 [4.0;5.0] antihypertensive drugs; glycated hemoglobin (HbA1c) was 7.5±1.5 %; estimated glomerular filtration rate (eGFR) was 73.1±21.8 ml/min / 1.73 m2 (CKD-EPI equation). Measurement of office BP, 24-h BP monitoring, renal artery (RA) Doppler, routine lab tests including determination of GFR (CKD-EPI), 24-h urine albumin excretion, and ELISA measurement of blood lipocalin-2, cystatin C, high-sensitive C-reactive protein (hsCRP), and asymmetric dimethylarginine (ADMA) were performed for all patients.Results    Incidence of increased RA resistive index (RI) was 39% despite the high rate of vasodilator treatment (93% for renin-angiotensin-aldosterone system inhibitors, 78% for calcium antagonists). According to a correlation and regression analysis, RA RI values were correlated with the kidney function (r=-0.46, p&lt;0.001 for eGFR, r=0.56; p=0.006 for lipocalin-2), age (r=0.54, p&lt;0.001), increases in concentrations of hsCRP (r=0.35, p&lt;0.001) and ADMA (r=0.39, p=0.028), the increase in vascular stiffness (r=0.59, p&lt;0.001 for pulse BP (PBP) as well as DM2 duration, and HbA1c (r=0.33, p&lt;0.001 for both). The independent association of RA RI with the age, PBP, and duration of DM2 was confirmed by the results of multivariate regression analysis. According to the ROC analysis, the threshold level of RA RI corresponding to a decrease in GFR &lt;60 ml / min / 1.73 m2 was ≥0.693 conv. units.Conclusion    In more than one third of patients with RAH in combination with DM2, increased renal vascular resistance was documented, which was closely associated with impaired kidney function, age, DM2 duration and severity, and markers of low-grade inflammation, endothelial dysfunction, and vascular stiffness. The value of RA RI ≥0.693 conv. units was a threshold for the development of chronic kidney disease (CKD).

Overweight and obesity are a worldwide common problem and are diagnosed with a body mass index (BMI) value in the range of 25.0-29.9 kg/m2 and ≥30.0 kg/m2, respectively. Obese patients are at high risk of developing concomitant diseases, such as hypertension, type 2 diabetes mellitus (DM2), hyperlipidemia, stroke and even some types of cancer. In the Russian Federation in 2016, the proportion of overweight people was 62.0%, with obesity - 26.2%. The authors performed an electronic search in the PubMed information database. Two search elements were used: «Semaglutide» and «Obesity». The search included studies published from the date of foundation of the database to August 2022. The search was limited only to the results of clinical trials. The authors obtained 26 results, but only the studies of SUSTAIN, PIONEER (Peptide Innovation for Early Diabetes Treatment) and STEP were considered, since they were original, randomized, controlled clinical trials conducted before the approval of semaglutide for the treatment of DM2 and obesity.

Aim: To investigate the effect of ursodeoxycholic acid (UDCA) on the degree of steatosis, indicators of carbohydrate, lipid metabolism, body weight in patients with type 2 diabetes mellitus (DM) in combination with non-alcoholic fatty liver disease (NAFLD)., Materials and Methods: A prospective cohort comparative study included 36 patients with DM and NAFLD. Patients received UDCA at a dose of 15 mg/kg/day for 6 months, and also followed the recommendations for lifestyle changes through diet and exercise. To compare the results obtained during the study, a control group of patients was recruited that met the criteria for inclusion in the study. The statistical analysis included an assessment of the normality of the distribution of quantitative indicators, followed by the determination of the mean values and standard deviation or medians and quartiles, depending on the nature of the distribution, the reliability coefficient was determined by the Student, by Wilcoxon. Statistical processing was carried out in the Statistica 10 program., Results: According to the results of the study, a positive trend was noted in the change in the severity of fatty hepatosis. During the study, a statistically significant decrease in the level of ALT, AST was achieved in the group receiving UDCA (Ursofalk). The results of our study showed that the inclusion of UDCA (Ursofalk) in complex hypoglycemic therapy provides an additional improvement in carbohydrate metabolism. The obtained indicators in the course of the study demonstrate the positive effect of UDCA on weight loss. The greatest result was achieved in reducing waist, which is a positive prognostic factor in reducing the development and progression of NAFLD, diabetes and cardiovascular diseases. Positive changes were observed in relation to the lipid profile., Conclusion: The study demonstrated the positive effect of the drug UDCA (Ursofalk) on reducing the degree of liver steatosis, on carbohydrate, lipid metabolism, body weight in patients with DM in combination with NAFLD.

Aim: To study myocardial perfusion in patients with coronary artery disease (CAD) with and without type 2 diabetes mellitus (DM) using volumetric computed tomography (VCT) of the heart with a pharmacological test with adenosine triphosphate (ATP)., Materials and Methods: The study included 93 patients, of which 18 had CAD with DM, and 50 had CAD without DM. All patients underwent one of the stress tests, cardiac VCT with ATP test, invasive coronary angiography, or CT coronary angiography. Left ventricle (LV) myocardial perfusion was evaluated for hypoperfusion zones and the calculation of semi-quantitative indices: decrease of LV myocardial density, LV myocardial perfusion index, transmural perfusion coefficient, and our proposed new indicator - myocardial perfusion reserve (MPR)., Results: The MPR index value in the hypoperfusion zones in patients with CAD and DM was 0.64 [0.62-0.66], in patients with CAD without diabetes 0.65 [0.63-0.66]; p =0.4; the value of the transmural perfusion coefficient in the areas of abnormal LV myocardial perfusion in patients with CAD and DM was 0.81 [0.80-0.86] versus 0.83 [0.80-0.85] in patients with CAD without DM ( p =0.6). More hypoperfusion segments were observed in patients with CAD and DM (33.3%) compared to those without DM (14%; p =0.029). The MPR index in the hypoperfusion zones in patients with CAD with intact coronary arteries (CA) and DM was 0.56 [0.54-0.60] versus 0.55 [0.54-0.62] in patients with CAD with intact CA without DM; p =0.2., Conclusion: In patients with CAD and type 2 DM, according to the VCT with ATP test, more foci hypoperfusion areas were detected, regardless of the severity of coronary artery involvement, compared with patients with CAD without DM, which may be due to the microangiopathy in the myocardium. The similarity of the MPR parameters in the hypoperfusion zones associated with hemodynamic stenosis of the CA and with intact CAs indicates the ischemic genesis of these zones. For citation: Soboleva GN, Minasyan AA, Gaman SA, Rogoza AN, Molina LP, Soboleva TV, Shariya MA, Ternovoy SK, Karpov YuA. Type 2 diabetes mellitus and coronary artery disease: features of perfusion volume computed tomography of the heart in a pharmacological test with adenosine triphosphate. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(4):309-315. DOI: 10.26442/00403660.2023.04.202158.

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high. To date, current medications for CKD haven't reduced enough the residual risk associated with inflammation and fibrosis in patients with type 2 diabetes. Here, in this review we present the results of FIDELIO-DKD, FIGARO-DKD trials and their pooled analysis FIDELITY, aimed to evaluate the effectiveness and safety of selective non-steroidal mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes with wide range stages of CKD. Modern pathophysiological aspects of mineralocorticoid receptor hyperactivation and features of their blockade by steroidal and nonsteroidal mineralocorticoid receptor antagonists are considered, differences in pharmacological effects between them are also discussed, finerenone benefits and its adverse events, demonstrated in randomized clinical trials are considered here. The probable mechanisms of early and delayed action of finerenone, which were realized in beneficial cardiovascular and renal outcomes in patients with type 2 diabetes with CKD, are presented here. Practical points for finerenone initiation and titration are indicated, aimed to minimize the hyperkalemia risk. Current guidelines for CKD treatment in patients with type 2 diabetes are analyzed, the finerenone placement in combined nephroprotective therapy is determined.

Administration of high doses of atorvastatin 80 mg/day and rosuvastatin 40 mg/day is a part of a standard algorithm for the treatment of patients at high and very high cardiovascular risk. This treatment allows reducing atherogenic low-density lipoprotein cholesterol (LDL-C) by approximately 50 % and decreasing the risk of cardiovascular diseases. Results of prospective studies with atorvastatin and rosuvastatin demonstrated a significant (45-55 %) decrease in LDL-C and triglycerides (11-50 %). This article focuses on analysis of evidence-based retrospective database for atorvastatin and rosuvastatin in prospective studies; reviewing a retrospective database of the VOYAGER study, including subgroups of patents with type 2 diabetes mellitus or hypertriglyceridemia; evaluation of the variability of the hypolipidemic response; and analysis of the risk for development of cardiovascular diseases and their complications with the statin treatment. Rosuvastatin at the highest daily dose of 40 mg/day was superior to atorvastatin 80 mg/day by the capability for decreasing LDL-C. Both statins showed a great variability in the degree of reducing triglycerides and exerted a minimal effect on high-density lipoprotein cholesterol. According to results of completed studies, rosuvastatin 40 mg/day also was superior to high doses of atorvastatin by tolerability and safety.

Background: Myocardial infarction (MI) in patients with diabetes type 2 (T2DM) occurs 1.5-3.0 times higher than in general population. Metformin is contraindicated for patients with T2DM and acute coronary syndrome due to the risk of developing lactic acidosis. Using metformin more than 48 hours of MI is a topical question, which will help to improve patient's safety., Aim: To evaluate the safety and quality of glycemic control using metformin in patients with T2DM during inpatient treatment for MIMATERIALS AND METHODS: The study included 161 patients with T2DM, who were hospitalized consecutively with acute MI with ST-elevation and underwent percutaneous coronary intervention (PCI). Average time of metformin initiation was 5th day from admission. Creatinine was assessed at admission and 48 hours after PCI. The acid-base balance and lactate were assessed at admission and on the 3rd day after the start of using metformin. Criteria for the effectiveness of glycemic control was the proportion of glycemic measurements in target range of 6.1-10.0 mmol/l during hospitalization ("hospital time in range", hTIR). hTIR >55% was considered to be a critical level. The long-term outcome was estimated at 365 days after hospitalization., Results: Metformin was prescribed to 99 patients (61%) ("M+"group) during the hospitalization, 62 patients were in "M-"group. Use of metformin was accompanied with better glycemic control in the «M+» group compared to the «M-»: mean glycemia 9.3 ± 1.6 vs 10.3 ± 2.3 mmol/l (p=0,002), SD 2.87 ± 1.1 vs 3.26 ± 1.8 (p=0,049), hTIR 60 ± 18% vs 48 ± 23% (p<0,001). There were clinically insignificant changes in acid-base balance on the 3rd day from the start of metformin use in the "M+" group, the lactate level did not increase. Use of metformin before to hospitalization with MI was not associated with an increased risk of developing acute kidney injury (AKI): RR 0.85 (0.37-1.96), p=0,691., Conclusion: Use of metformin in patients with T2DM and acute MI is associated with better glycemic control. Carrying out angiography in patients, treated with metformin before the hospitalization, is not accompanied by an increased risk of developing AKI. Appointment of metformin in 3-7 days after angiography does not lead to an increase level of lactate and significant deviations in acid-base balance.

Background: Numerous studies indicate a high incidence of various disorders of carbohydrate metabolism against the new coronavirus infection. These disorders aggravate the course of infection and increase mortality. Thereby, analysis of risk factors for unfavorable outcomes and assessment of the long-term consequences of COVID-19 in patients with impaired carbohydrate metabolism is of great importance., Aim: To investigate the association between carbohydrate metabolism disorders in COVID-19 patients and mortality, course of infection, long-term consequences, as well as to identify risk factors for an unfavorable disease course., Materials and Methods: A retrospective analysis of data from the combined multicenter non-interventional real-world AKTIV and AKTIV 2 registries was performed. The sample included 9290 patients who had COVID-19 with varying severity from June 29, 2020, to November 29, 2020 (AKTIV) and from October 01, 2020, to March 30, 2021 (AKTIV 2). The patients were divided into 3 groups: Group 1 - patients with intact carbohydrate metabolism, n=6606; Group 2 - patients with newly diagnosed hyperglycemia (NDH), n=1073; Group 3 - patients with a history of type 2 diabetes mellitus (DM2), n=1611. The groups were assessed for clinical and laboratory parameters, comorbidities, mortality, carbohydrate metabolic status, and well-being during the infection and at 12 months., Results: The prevalence of carbohydrate metabolism disorders (CMD) was 28,9%, with DM2 patients accounting for 17,3% and patients with newly diagnosed hyperglycemia (NDH) for 11,6%. The mortality rate of patients with hyperglycemia of any origin was 10.6%, which was significantly higher compared to patients without hyperglycemia (3,9%). The probability of lethal outcome increased 2,48-fold in the group of patients with DM2 and 2,04-fold in the group of patients with NDH. At the same time, the probability of a lethal outcome decreased 2,94-fold in patients without CMD. At 12 months, patients with CMD showed a significantly higher frequency and longer persistence of complaints. This trend was more pronounced in patients with DM2 than in those with NDH. Only 1,7% of patients from the NDH group had type 2 diabetes and were receiving oral hypoglycemic medications one year after the infection. A prognostic model was developed to determine the risk of lethal outcome. The model included such known predictors as concomitant ischemic heart disease, history of myocardial infarction or stroke, blood glucose level, and age., Conclusion: Carbohydrate metabolism disorders aggravate the course of COVID-19 and increase mortality. One year after infection, patients with DM2 and NDH were more likely to have symptoms typical for post-COVID syndrome, and NDH resolved in most cases after the infection.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) and considered one of the leading causes of vision loss worldwide. The choroid supplies blood to the retina, photoreceptors and the retinal pigment epithelium, it is essential for metabolic exchange in the retina. Many experimental studies have reported that choroidal pathology in diabetic patients may play a role in the development of DR. Choroidal thickness (CT) can be used to assess the vascularization of the choroid. Choroidal vascularity index (CVI) is also used as a marker in assessment of choroidal vascularization. Many studies have been conducted to evaluate choroidal changes in various eye diseases. However, the data on CT in DM patients, especially in those with DR, are conflicting. Thus, the choroidal status in diabetic patients with or without DR remains controversial. In this systematic review we analyze a number of articles dedicated to the relationship between structural changes in the choroid in patients with diabetes mellitus and diabetic retinopathy of different stages, paying particular attention to choroidal thickness and certain other parameters that allow assessment of choroidal changes.

Objective: The purpose of the present double-blind, placebo-controlled, randomized clinical trial was to evaluate the efficacy and safety of Cytoflavin in patients with diabetic polyneuropathy (DPN)., Material and Methods: Investigational therapy was administered in two steps: intravenous infusions of experimental drug/placebo for 10 days followed by oral administration for 75 days. In 10 clinical centers, 216 patients aged 45-74 years with a diagnosis of type 2 diabetes mellitus, symptomatic distal sensorimotor DPN, confirmed no earlier than 1 year before screening, on stable therapy (no change of drugs and doses) by oral hypoglycemic drugs, intermediate-acting, long-acting or extra-long-acting insulin, and/or GLP-1 receptor agonists., Results: By the end of treatment, the change of the Total Symptom Score (TSS) in the experimental group was -2.65 points, in the placebo group -1.73 points ( p <0.001). Improvement of symptoms in the experimental group was achieved regardless of the degree of compensation for type 2 diabetes (both in those with Hb1Ac <8.0% and in those with Hb1Ac ≥8.0%), but demonstrated better results in patients with less severe baseline symptoms (TSS <7.5). Improvement in the components of the TSS scale «paresthesia» and «numbness» occurred as early as on day 11 of therapy; by the end of treatment, a significant decrease in the «burning» component was also demonstrated. The experimental drug had a positive safety profile., Conclusion: Cytoflavin, intravenous solution and enteric-coated tablets (SPTF Polysan Ltd.) is indicated for the symptomatic treatment of DPN.

The aim of work is identification and evaluation of clinical factors influencing the dynamics of progression of chronic kidney disease in elderly patients with type 2 diabetes. In a population sample of elderly patients with type 2 diabetes, a cross-sectional observational study of clinical indicators of the standard program of dispensary observation was performed. Primary medical data were collected using the AWPE 2.0 program. 118 protocols of outpatient consultations, including 69 clinical indicators, were selected according to the compliance criteria. To assess the dynamics of the progression of chronic kidney disease, the original calculated diagnostic parameter «Glomerular filtration rate reduction index» (GFR RI) was used. A detailed clinical justification of the calculated diagnostic parameter GFR RI is given; correlations between quantitative and qualitative clinical indicators and GFR RI in a sample of elderly patients with type 2 diabetes are determined; statistically significant differences in clinical factors were revealed in groups identified by the rate of progression of CKD with a threshold value of 3,83 ml/min on 1,73 m2 per year, including medicamental. The proposed diagnostic parameter GFR RI allows us to give an objective assessment of the dynamics of the progression of CKD in elderly patients with type 2 diabetes; when identifying the groups of «slow» and «fast» progression of CKD, significant differences in the following clinical factors were revealed: the level of glycemia, BMI, the experience of diabetes and insulin therapy, the total dose of insulin and sulfonylureas, the presence of concomitant hypertension.

Objective: To analyze the results of emergency surgery in COVID-19 patients with viral pneumonia., Material and Methods: A retrospective study included 75 COVID-19 patients who underwent emergency surgical interventions. Comorbidities included cardiac diseases, nonspecific lung diseases, type 2 diabetes, kidney diseases, overweight, and cancer. Various combinations of these diseases were also noted., Results: We carried out emergency surgeries for abdominal, thoracic, soft tissue and venous diseases. Postoperative mortality was 42.6%. The best results were obtained after minimally invasive interventions without mechanical ventilation. Extended surgery with mechanical ventilation was followed by fast progression of pneumonia according to clinical and CT data., Conclusion: Surgical interventions undoubtedly worsen prognosis of treatment in patients with COVID-19. Emergency minimally invasive surgery without mechanical ventilation can reduce the risk of unfavorable outcomes in patients with viral pneumonia, especially in case of concomitant cancer and other severe comorbidities.

Diabetic retinopathy (DR) occupies a special place among the causes of progressive decline and loss of visual acuity, it significantly impairs the quality of life and viability of elderly patients, and allostatic load is considered its integral indicator. However, the allostatic load in patients suffering from diabetic retinopathy, as well as in other ophthalmological diseases, has not been extensively studied, so biomarkers characterizing the allostatic load of patients with diabetic retinopathy remain unknown., Purpose: This study investigates the allostatic load in patients with diabetic retinopathy and attempts to identify the biomarkers that determine it to the fullest extent., Material and Methods: Allostatic load was studied in 78 elderly patients with diabetic retinopathy and type 2 diabetes mellitus, and in 62 patients with type 2 diabetes mellitus without diabetic retinopathy. Allostatic load was evaluated by analyzing systolic and diastolic blood pressure, body mass index, glycated hemoglobin, total cholesterol, triglycerides, albumins, C-reactive protein, homocysteine in the blood and glomerular filtration rate., Results: It was found that in patients with diabetic retinopathy the most pronounced and statistically significant excess was in the content of glycated hemoglobin in the blood up to 10.2% versus 7.4%, and homocysteine up to 15.5 mmol/L versus 7.9 mmol/L compared to patients with diabetes mellitus without diabetic retinopathy, respectively. The value of the allostatic index was significantly higher in patients with diabetic retinopathy, amounting to 4.6±0.4 points, versus 2.9±0.3 points in patients with diabetes mellitus without the studied ophthalmic pathology ( p <0.001). Factor analysis made it possible to identify biomarkers of allostatic load in patients with diabetic retinopathy - glycated hemoglobin, homocysteine, triglycerides and albumins., Conclusion: The identified biomarkers can be used for assessing the viability and the effectiveness of rehabilitation measures carried out in patients with diabetic retinopathy.

Sleep disorders are very common in patients with type 2 diabetes (T2DM) and psychiatric disorders. Sleep disturbances can be both an independent condition and are one of the symptoms in the structure of a psychopathological syndrome. The negative impact of sleep disorders and mental disorders on the course of T2DM is known from numerous publications. This article presents current information on the mutual influence of mental disorders and sleep disorders on the course and prognosis of T2DM.

Objective: To study the effect of the combined drug Cytoflavin on the mechanisms of nonspecific inflammation in the treatment of diabetic polyneuropathy (DPN) with an assessment of the dynamics of the TNF-α index., Material and Methods: An open comparative prospective observation of patients with a history of DPN for more than 5 years and a high level of TNF-α was carried out. All patients underwent basic oral combined hypoglycemic therapy, the main group used the combined drug Cytoflavin 10 ml (per 200 ml 0.9% NaCl) for 10 days, followed by the transition to the enteral form of the drug, 2 tablets 2 times a day for 1 months The main indication for the appointment of Cytoflavin was the presence of comorbid pathology in the form of cerebrovascular disease in all studied patients. The severity of clinical symptoms of DPN, the quality of life (QOL) of patients, as well as the dynamics of the level of TNF-α as an indicator reflecting the process of inflammation were assessed., Results: As a result of the treatment in the study group, there was an improvement in QoL, a decrease in the severity of sensory complaints and a decrease in the level of TNF-α, which may indicate a possible anti-inflammatory mechanism of the combined drug Cytoflavin., Conclusion: Cytoflavin can inhibit inflammation and reduce the severity of sensitive disorders in patients with DPN.

Purpose: This study evaluates the diagnostic capabilities and the prognostic value of nailfold capillaroscopy data of patients with diabetic retinopathy (DR) to develop an algorithm of monitoring patients with type 2 diabetes mellitus., Material and Methods: The study involved 90 patients (mean age 67 years), among them 31 with nonproliferative diabetic retinopathy, 29 patients with proliferative DR and 30 patients without retinopathy. In addition to conventional ophthalmological examination, optical coherence tomography angiography (OCTA) on the Optovue RTVue-100 device (USA) was performed using en face vessel density protocol to examine the state of the microvasculature of the superficial and deep layers of the vascular plexus of the central retinal zone, as well as nailfold capillaroscopy using computerized capillaroscope KK-01 (ZAO Centr Analiz veshhestv, Russia)., Results: The cut-off points for detecting the presence of non-proliferative DR (capillary network density below 38.4%, arterial velocity below 512 mm/s and venous blood flow below 585 mm/s), and the presence of proliferative DR (capillary network density below 30.4%, the arterial velocity below 451 mm/s and the venous blood flow below 441 mm/s) were identified according to ROC-analysis of nailfold capillaroscopy data. In the diagnosis of proliferative DR the capillary network density parameter has a slightly higher diagnostic information value (AUC=0.963) than arterial blood flow velocity (AUC=0.941) or venous blood flow velocity (AUC=0.909). Using the identified critical parameters for predicting the initial and proliferative DR, we created a diagnostic algorithm involving a comprehensive assessment of all characteristics., Conclusion: The study revealed that nailfold capillaroscopy indicators (capillary network density, velocity of arterial and venous blood flow) have high diagnostic information value for detecting both non-proliferative and proliferative retinopathy. We constructed mathematical models for predicting DR with an accuracy of predicting the presence of a non-proliferative stage in 92.2% of cases and a proliferative stage in 94.4% of cases. For practical use in clinical environment, we created a computer program calculating the results of DR predictions according to nailfold capillaroscopy data.

Type 2 diabetes mellitus is one of the most common non-infectious diseases in the world. Among people with type 2 diabetes, patients of the older age group predominate: 60,5% of all patients are over 65 years old, and the peak prevalence is at the age of 65-69 years. The treatment of this pathology in elderly patients has certain features, which is associated with a high level of polymorbidity in these patients. Therapy for type 2 diabetes should be aimed not only at compensating the level of glycemia, but also at treating and preventing complications of diabetes, and improving the quality of life of patients. The choice of hypoglycemic therapy should take into account the effect of drugs on the cardiovascular system and kidney function, as well as the risk of hypoglycemia, which is more common in older people and affects the cognitive function of such patients. This review discusses the possibilities of using various groups of antidiabetic drugs in elderly and old patients.

Aim      To evaluate cardiometabolic effects of empagliflozin in patients with ischemic heart disease and type 2 diabetes mellitus (DM) following elective percutaneous coronary intervention (PCI).Materials and methods Patients meeting the inclusion/non-inclusion criteria were randomized into two groups of equal number using simple randomization with successively assigned numbers. Group 1 included 37 patients (18 men and 19 women) who gave their consent for the treatment with empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy. The drug administration started one month prior to the elective PCI and continued for the next 11 months (treatment duration, 12 months). Group 2 (comparison group) consisted of age- and DM duration-matched patients (37 patients; 18 men and 19 women) who continued on their hypoglycemic therapy previously prescribed by endocrinologists during the entire study period. Before the study, 36.11 % patients of the empagliflozin group and 27.03 % of the comparison group had unsatisfactory glycemic control as shown by the level of glycated hemoglobin (HbA1c).Results At 6 and 12 months of the study, fasting glycemia and HbA1c were significantly lower in the empagliflozin treatment group. The groups were comparable by the incidence of adverse outcomes: 8 (22.24 %) patients in the empagliflozin group and 10 (27.04 %) patients in the comparison group (р=0.787). The 12-month empagliflozin treatment reduced total cholesterol (C) by 5.56 % (p&lt;0.05), low density lipoprotein (LDL) C by 3.67 % (p&lt;0.05), visceral adipose tissue area (VATA) by 5.83 % (p&lt;0.05), and subcutaneous adipose tissue area (SATA) by 3.54 % (p&lt;0.05).Conclusion      The empagliflozin treatment for 30 days prior to and after elective PCI can enhance the effectiveness of myocardial revascularization due to the demonstrated beneficial cardiometabolic effects.

Aim      To study early manifestations of left ventricular (LV) and right ventricular (RV) myocardial remodeling in high-risk patients.Material and methods  Intracardiac hemodynamics was studied by equilibrium radionuclide ventriculography (ERVG) in 83 patients (mean age, 61.1±8.9 years) with preserved LV ejection fraction according to echocardiography data, a body weight index (BWI) &gt;25 kg /m2, obesity, and type 2 diabetes mellitus (DM2). Parameters of intracardiac hemodynamics were compared in patients with different degrees of obesity and DM2 durations in age groups of younger and older than 60 years.Results All patients had both LV and RV diastolic dysfunction. The diastolic dysfunction progressed with age and DM2 duration, primarily by the restrictive type. The increase in BWI, in contrast, was associated with increases in ventricular volumetric parameters. It was noted that specifically modifiable risk factors (obesity and DM2), but not the age, mostly facilitated the impairment of RV relaxation.Conclusion      The strategy of normalizing the body weight and carbohydrate metabolism is priority in combatting the development and progression of chronic heart failure in high-risk group patients.

Patients with diabetes mellitus (DM) and coronary heart disease belong to a group with a very high risk of developing cardiovascular disease. In patients with coronary atherosclerosis, DM increases the risk of ischemic events by 2-4 times. Apparently, increased antithrombotic therapy has an advantage in patients with DM who have had myocardial infarction. However, until recently it was not clear there is such an advantage in patients with DM and stable coronary artery disease without prior myocardial infarction. The addition of ticagrelol to monotherapy of acetylsalicylic acid reduces the risk of major cardiovascular events in patients with type 2 DM and stable coronary artery disease undergoing percutaneous coronary intervention, if patients have a high risk of ischemic events.

Sodium-glucose cotransporter inhibitors updated their position in the therapy of patients with type 2 diabetes mellitus due to proven nephro- and cardioprotective effects. The DAPA-CKD study, performed among individuals with CKD of various etiologies, was also conducted in a mixed population, including patients without type 2 diabetes, showed the ability of dapagliflozin to reduce the risk of the primary combined endpoint (eGFR<15 ml/min/1.73 m 2 , the need for chronic dialysis or kidney transplantation, time to renal or cardiovascular death), and certain secondary endpoints. Due to the inclusion of dapagliflozin into the treatment of the patients with CKD of not only the diabetic origin and the expected subsequent significant expansion of the patient population with indications for the use of this drug, the review of the results of the sub-analyses of DAPA-CKD study may be of interest to the clinicians.

Obesity and type 2 diabetes mellitus (DM 2) are two interrelated metabolic diseases widespread throughout the developed world. However, up to 30% of individuals with a long history of obesity do not have a carbohydrate metabolism disorder. This article presents the results of a multi-year study of adipose tissue biology in obese individuals with DM 2 compared with individuals with the same history of obesity without DM 2. Comparative analysis of hormonal, cellular, and genetic factors in two groups of patients showed that DM 2 occurs in individuals with abnormal proliferation and adipogenic differentiation of mesenchymal stem cells (MSCs) of adipose tissue. It leads to adipocyte hypertrophy and inflammatory infiltration of adipose tissue macrophages, resulting in increased insulin resistance and diabetogenic effects. These disorders are due to abnormal expression of genes responsible for the proliferation and adipogenic differentiation of MSCs. The study of the possible reversibility of abnormal changes in adipose tissue MSCs in obese patients after significant weight loss and DM 2 remission appears to be a promising research direction. The ability to control adipose tissue progenitor cells may represent a new target for treating and preventing metabolic disorders in obesity.

Aim      To study the incidence and clinical and pathophysiological features of diastolic dysfunction (DD) and chronic heart failure with preserved ejection fraction (HFpEF) in patients with resistant arterial hypertension (RAH) associated with type 2 diabetes mellitus (DM).Material and methods  A cross-sectional study that included 36 patients with RAH associated with type 2 DM (mean age, 61.4±6.4 years; 14 men) was performed. Measurement of office and 24-h blood pressure (BP), standard echocardiography with assessment of diastolic function (DF) and ventricular-arterial coupling, doppler ultrasound imaging of renal blood flow, and laboratory tests (blood glucose, glycated hemoglobin, blood creatinine, tumor necrosis factor α (TNF-α), brain natriuretic peptide (BNP), type 2 and type 9 matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of MMP 1 (TIMP-1), 24-h urine protein test, and 24-h urine volume test were performed for all patients. HFpEF was diagnosed according to criteria of the American Society of Echocardiography and the European Society of Cardiology 2019, and the Russian Clinical Guidelines on Diagnosis and Treatment of CHF 2017 and 2020.Results All patients had DD. Incidence of HFpEF detection according to the Russian Guidelines 2017 was 100%; according to the Russian Guidelines 2020, that included a required increase in BNP, and according to the criteria of the European Guidelines 2019, this incidence was 89 %. In 55.6 % of patients, DD corresponded to grade 2 (pseudonormal type). According to the correlation analysis, the DF impairment was associated with increases in pulse BP, myocardial mass, arterial and left ventricular elastance (arterial wall and left ventricular elasticity), basal glycemia and DM duration, MMP-2 level, proteinuria, blood creatinine, renal vascular resistance, and also with decreases in 24-h urine volume, MMP-9, TIMP-1, and TIMP-1/MMP-2. Significance of the relations of mean E / e' ratio with nighttime pulse BP, MMP-9, and 24-h urine volume were confirmed by results of multiple linear regression analysis. Increased myocardial and vascular wall stiffness, concentrations of MMP-2 and TNF-α and reduced 24-h urine volume were associated with progressive impairment of DF.Conclusion      The combination of RAH and DM-2 is characterized by an extremely high incidence of DD that determines a great prevalence of HFpEF. The development and progression of DD in such patients are closely related with a complex of metabolic, proinflammatory and profibrotic biomarkers, increased vascular wall stiffness, pronounced left ventricular hypertrophy, and with structural and functional alterations in kidneys.

Аim. To investigate the clinical characteristics and quality of treatment (according to the national guidelines) of patients with arterial hypertension (AH) and chronic kidney disease observed in primary health care., Materials and Methods: The study was carried out on the basis of the AH registry data (n=43 133; 20052019 years). Glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula; renal structure and albuminuria were not evaluated. The analysis was performed using the SPSS software (version 22; SPSS Inc)., Results: The creatinine level was assessed in 60% of patients, 23.6% of them had decreased eGFR60 ml/ min/1.73 m2. The incidence of co-morbid CVD and type 2 diabetes in patients with hypertension increased markedly with a decrease in eGFR (14 groups): the incidence of coronary artery disease increased 1.8 times (up to 72.5%), myocardial infarction 1.7 times (up to 20.6%), chronic heart failure 2 times (up to 84.0%), atrial fibrillation 10 times (up to 18.3%), history of stroke 3.7 times (up to 15.3%) and type 2 diabetes 2.4 times (up to 32.8%). Achievement of target goals of CV risk factors was not enough: systolic BP less than 50% of patients, triglycerides less than 7%, LDL-C in high and very high CVD risk patients less than 13%., Conclusion: Conducting timely assessment of renal function, drug therapy and lifestyle changes in patients with AH and decreased renal functional could prevent severe kidney damage, the development of CV complications, chronic renal failure and reduce mortality.

Metformin is a first-line antidiabetic drug for the treatment of type 2 diabetes mellitus (DM2); its molecular target is AMP-activated protein kinase (AMPK), which is involved in many metabolic processes. Metformin not only reduces blood glucose levels and improves insulin sensitivity, but also inhibits lipolysis and reduces cardiovascular risk in patients with DM2. In recent years, it has been proven that metformin slows down the aging process, stimulates hair growth, eliminates cognitive impairment, and also has an antitumor effect. Most basic studies have shown that metformin inhibits the growth of tumor cells and promotes cellular apoptosis, while clinical studies show contradictory results. This discrepancy can be explained by the difference in the concentration of metformin between basic and clinical studies. The maximum daily dose of metformin for patients with DM2 is 2500 mg / day, and the dose used in basic research was much higher. Metformin directly activates the AMPK signaling pathway, inhibits the production of reactive oxygen species, induces the activation of mTORC1, inhibits cyclin D1, which leads to a reduction in the risk of the occurrence and development of malignant neoplasms. In addition, metformin indirectly inhibits tumor growth, proliferation, invasion and metastasis by reducing the concentration of glucose in the blood, insulin resistance, as well as by reducing inflammation and affecting the tumor microenvironment. Glycolysis plays an important role in the energy metabolism of tumors, and metformin is able to have an inhibitory effect on it. Currently, studies of the mechanism of antitumor effects of metformin are becoming more extensive and in-depth, but there are still some contradictions.