BACKGROUND: Studies have shown a high incidence of metabolic disorders and cardiovascular diseases in patients with primary hyperparathyroidism (PHPT). PHPT is usually diagnosed in people of age over 50 years and therefore age-associated changes of metabolism should be excluded. Researching predictors of cardiovascular pathology contributes to choosing optimal approaches to personalized patient management.

AIM: To determine the features of metabolic disorders in patients of various age groups with confirmed active stage of PHPT.

MATERIALS AND METHODS: A single-center observational retrospective comparative study of patients with active PHPT at the age of 18-49 years (Group 1, n=66) and over 50 years (Group 2, n=290) was carried out. The exclusion criteria for both groups were: persistent PHPT or recurrence after surgical treatment of the disease in history; clinical/genetically confirmed multiple endocrine neoplasia syndrome; for Group 1 — pregnancy, lactation. The assessment of laboratory parameters of mineral, carbohydrate, fat and purine metabolism obtained during a hospital examination was carried out, the frequencies of various metabolic disorders were determined and compared between age groups.

RESULTS: There were no significant differences in parathyroid hormone and serum calcium levels between age groups, however, there were more severe hypercalciuria, a tendency to active bone metabolism and lower vitamin D level in Group 1. Patients of Group 2 had statistically significantly lower glomerular filtration rate and a higher frequency of bone complications. In the same group glycaemia and triglycerides levels were higher (the latter difference has the level of a statistical tendency). These patients also had a higher body mass index and, as a result, a higher incidence of obesity (37% vs 20%, p=0.006) and diabetes mellitus type 2 (12.5% vs 3%, p=0.013). At the same time, patients did not significantly differ in the rates of hypercholesterolemia (62% in Group 1 vs 70% in Group 2, p=0.228), hypertriglyceridemia (27% vs 32%, p=0.433) and hyperuricemia (42% vs 50%, p=0.302), significantly exceeding similar indicators in the general Russian population.

CONCLUSION: Carbohydrate disorders are more often observed in patients older than 50 years, providing an increased prevalence of diabetes mellitus type 2 among patients with PHPT compared with the general population. The high incidence of various types of dyslipidemia and hyperuricemia in the primary parathyroid pathology has no age specific features. Thereby these disorders are significant risk factors of cardiovascular diseases, even in young people with PHPT.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which includes changes from hepatic steatosis and nonalcoholic steatohepatitis to fibrosis and cirrhosis. Attempts to find noninvasive markers of liver fibrosis have led to a variety of scales, diagnostic algorithms, and imaging techniques. Individual studies have analyzed the relationship between the FINDRISC scale and hepatic steatosis and concluded that this questionnaire can be used as part of population screening to identify individuals at risk for hepatic steatosis. However, our review of the literature did not reveal any clinical studies on the use and effectiveness of the FINDRISC in liver fibrosis screening.

AIM: To evaluate diagnostic value of FINDRISC for liver fibrosis detection.

MATERIALS AND METHODS: The study enrolled patients aged 40–60 years from unorganized outpatient population. The sample of patients was formed randomly according to the inclusion and noninclusion criteria. All patients were assessed with standard anthropometric parameters. The FINDRISC questionnaire was used. All patients underwent transabdominal ultrasound examination of the liver and transient liver elastometry. The degree of steatosis was evaluated using Hamaguchi ultrasound scale.

 RESULTS: The study included 100 patients. An increased risk of type 2 DM (≥7 points) was detected in 68% of patients using the FINDRISC scale. Liver steatosis was diagnosed in 41% of patients. Median values of hepatic elastic modulus by transient elastometry were 4.50 (4.00; 5.25) kPa. At the same time, liver elasticity modulus values ≥5.9 kPa were registered in 11 (11.0%) patients. When analyzing the array of sensitivity and specificity values using the ROC-curve, it was found that for the FINDRISC scale the maximum LR+ and the minimum LRvalues were observed when the number of points on the indicated scale exceeded 10. At this cutoff, the FINDRISC scale had a sensitivity of 81.8% and specificity of 61.8% for detecting liver fibrosis (liver modulus of elasticity ≥5.9 kPa). The scale was of good diagnostic value (AUC 0.699; 95% CI 0.530–0.815).

CONCLUSION: In an unorganized sample of patients aged 40–60 years the FINDRISC can serve as a diagnostic tool for liver fibrosis and steatosis. Sum of FINDRISC scores >10 allowed to diagnose liver fibrosis (liver elastic modulus ≥5.9kPa) with sensitivity 81.8% and specificity 61.8%. The probability of absence of hepatic fibrosis with FINDRISC scale values <10 was 96.5%.

BACKGROUND: The decisive importance of the sympathetic and parasympathetic nervous system in maintaining vegetative homeostasis requires the determination of sensitive non-invasive parameters of multidimensional outpatient monitoring of cardiorespiratory adaptation under various physiological and clinical conditions, taking into account the function of external respiration (FER), compound body composition and heart rate variability (HRV).

AIM: To identify concomitant changes in HRV, HR and compound body composition in young people as markers of cardiorespiratory adaptation and rehabilitation.

MATERIALS AND METHODS: On the basis of the Kuban State Medical University, a single-centre, interventional, cross-sectional, single-sample, comparative, uncontrolled study of a general group of young people in which respiratory parameters and parameters of the compound body composition were determined. Some individuals in this group additionally underwent Holter monitoring of the electrocardiogram (ECG) at short intervals.

RESULTS: In young people, a change in the compound body composition with an increase in total fat mass, visceral and body fat is associated with a decrease in respiratory function (a decrease in the Tiffno index, a decrease in the maximum middle-expiratory flow — MMEF), manifested by a decrease in HRV (according to the TI indicator), the absence of an increase in the autonomic regulation circuit (according to SDNN indicator), a decrease in parasympathetic activity (in terms of rMSSD) and the absence of sympathetic activation (in terms of SDANN). Positive shifts in the form of an increase in trunk muscles, the total amount of water and a decrease in the total fat mass are accompanied by an increase in lung capacity, forced expiratory volume in the first second and a change in HRV with sympathetic (in terms of LF / HF, SDANN) and parasympathetic activation (in terms of rMSSD), an increase in HRV (in terms of TI) and an increase in the autonomic regulation circuit of the vegetative nervous system (in terms of SDNN).

CONCLUSION: Accurate and rapid diagnostics of vegetative homeostasis requires a comprehensive correlative analysis of the parameters characterizing HRV in short recordings, the compound composition of the human body and respiratory function.

BACKGROUND: Obesity and androgen deficiency (AnD) are characterized by similar disturbances in metabolic parameters, the presence of signs of insulin resistance, metabolic syndrome, the risk of developing cardiovascular diseases (CVD) and vascular complications. These facts indicate the possibility of the presence of common mechanisms that determine the predisposition to the development of obesity and AnD, which may include genetic factors, in particular, the rs4646994 polymorphism of the ACE gene, which, according to recent data, is associated with the risk of developing CVD, hypertension, and obesity.

AIM: To study the association of the carriage of polymorphic variants of the rs4646994 locus of the ACE gene with the features of anthropometric and androgenic status in men.

MATERIALS AND METHODS: In the period from April 2020 to October 2021 there were observed male patients aged 18–75 years old, who were hospitalized in a therapeutic hospital because of comorbid somatic pathology (hypertension, coronary heart disease, dorsopathy, vegetative-vascular dystonia, gastroesophageal reflux disease, and others). Anthropometry, a study of the content of hormones of the reproductive system in the blood serum using enzyme-linked immunosorbent assay (ELISA), as well as a genetic study for the carriage of polymorphic variants of the rs4646994 locus of the ACE gene by the polymerase chain reaction (PCR) method, followed by electrophoresis of PCR products, were carried out. 

RESULTS: 82 patients took part in research. According to the results of genetic analysis, 17 people were assigned to the group of homozygotes for the wild type (I/I, G1), 41 people were assigned to the group of heterozygotes (I/D, G2), and 41 people were assigned to the group of homozygotes for the mutant allele (D/D, G3) 24 people. Body weight, chest circumference, waist and hips, body mass index in patients carrying the D allele of the rs4646994 polymorphism were statistically significantly higher than in I/I homozygotes. Differences in hormonal status also turned out to be statistically significant: patients from G1 compared with G2 and G3 had higher levels of total testosterone; from G1 compared to G3 — a higher level of free testosterone.

CONCLUSION: An association of the carriage of the D allele of the rs4646994 polymorphic locus of the ACE gene with overweight and ADI was revealed.

BACKGROUND: The problem of metabolic syndrome is considered a demographic catastrophe. According to WHO experts,

«by 2025, the prevalence of metabolic syndrome (MS) in the world will amount to more than 300 million people, and in the next 25 years it is expected to increase by 50%.» The pathophysiological mechanisms of MS formation and the role of unhealthy diet on the development of intestinal dysbiosis, mitochondrial insufficiency remain unclear.

AIM: To study the effect of unhealthy diet on the state of the intestinal microbiota and the development of metabolicmitochondrial insufficiency in the formation of a multi-organ metabolic syndrome, evaluation of ways of correction.

MATERIALS AND METHODS: Clinical picture assessment, anthropometric data (body mass index), laboratory results (glucose, cholesterol and fractions) were carried out in patients with MS, triglycerides, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, lipid peroxidation indicators: malondialdehyde, diene conjugates, schiff bases, hydroperoxides, catalase, superoxide dismutase, succinate dehydrogenase (ASDH), α-glycerophosphate dehydrogenase (α-AGFDH). Hemorheological parameters were evaluated by the apparent viscosity of blood, the yield strength, the aggregation coefficient of erythrocytes and platelets. The microbiota and microbiome of the intestine were evaluated by species, strain composition and the level of metabolites-propionic, butyric, acetic acid, lipopolysaccharides, peptidoglycans. A questionnaire was conducted to study the nature of nutrition.

RESULTS: The study included 128 patients with MS and 25 healthy individuals. According to medical outpatient records from anamnesis, questioning of each patient, complaints and clinical picture, 26.2% of patients had type 2 diabetes, 3.74% of men had erectile dysfunction, 7.5% of women had polycystic ovaries, 15.1% had night apnea syndrome, 8.7% hyperuricemic syndrome, 96.5% of patients had metabolic fatty liver steatosis. According to the results of the survey, it was revealed that 99.8% of patients adhered to an unhealthy and unbalanced, high-calorie diet, 46.4% of patients had a low level of physical activity, 48.7% had an average. The revealed disorders of lipid, carbohydrate metabolism, microbiota and intestinal microbiome were associated with increased lipid peroxidation, decreased levels of antioxidant defense enzymes, indicators reflecting mitochondrial function against the background of hemorheological disorders.

CONCLUSION: In multi-organ MS, unhealthy diet can be considered as a targeted risk factor triggering pathophysiological mechanisms at the level of the intestinal microbiota, followed by a cascade of metabolic disorders in the form of activation of lipid peroxidation with inhibition of antioxidant defense enzymes, the development of multi-organ mitochondrial insufficiency and the development of latent hemorheological syndrome. The revealed metabolic complex obviously constitutes a multiorgan morphological cluster underlying the development of multi-organ metabolic syndrome. Based on the identified disorders, pathogenetically justified correction of MS should include a balanced diet with mitochondrial protective therapy.

The literature review presents the results of modern studies of the relationship between diet and intestinal microbiota in the regulation of metabolic disorders. Metabolic syndrome, which is a symptom complex that combines abdominal obesity, insulin resistance, hyperglycemia, dyslipidemia and arterial hypertension, remains an important problem, being a risk factor for cardiovascular, neurodegenerative, oncological diseases and the development of type 2 diabetes mellitus. Although the pathogenesis of the metabolic syndrome has not yet been fully elucidated, it is known that visceral obesity and its associated complications, such as dyslipidemia and increased levels of pro-inflammatory cytokines, play a central role. The article presents data on the impact of the consumption of certain food products, the inclusion of plant biologically active substances (flavonoids, polyphenols, etc.) in the diet, as well as the use of elimination diets with the exclusion of carbohydrates or fats from the diet, on reducing the risk of cardiovascular accidents, levels of fasting glucose, total cholesterol, LDL, triglycerides, C-reactive protein, leptin, insulin, reduction in body weight and waist circumference, reduction in the level of circulating endotoxins and changes in the activity of immunocompetent cells. Data are presented on the possible influence of the intestinal microbiota in maintaining inflammation and the formation of degenerative changes in the body. The role of changes in the ratio of the levels of pathogenic microflora, bifidobacteria and lactobacilli in the formation of a pathological condition is shown.

Obesity and type 2 diabetes mellitus (T2DM) are major problems for public health all over the world. According to retrospective research, the prevalence of obesity has doubled in more than 70 countries since 1980, as well as the prevalence of obesity complications (atherosclerotic cardiovascular diseases, nonalcoholic fatty liver disease and their complications. There are many drug therapies for T2DM, but it is difficult to achieve a stable, clinically relevant effect on a long-term basis. The fact that a patient has both conditions makes it difficult to optimize carbohydrate metabolism and to achieve normal body weight. Many antidiabetic drugs cause weight again, which, in turn, contributes to the growth of insulin resistance (IR) and requires further intensification of therapy.

In the last few years, there is a growing evidence of the relationship between the gut microbiota (GM), obesity and T2DM. There has been a steady growth of interest in such medical technology as fecal microbiota transplantation (FMT) in the world. Since there is data on the association of the gut microbiota (GM) with the development of IR and T2DM, the possibility of FMT can potentially be one of the new methods of treatment. This review presents the current state of the problem and discusses the possibility of modifying GM as a therapeutic strategy in obesity and T2DM with an accent on autologous fecal microbiota transplantation.

The medical and social significance of cardiovascular diseases remains high. One of the factors that determine cardiovascular risks is metabolic syndrome. As a result of excessive accumulation of lipid and carbohydrate metabolism products in metabolic syndrome, oxidative (oxidative) stress develops. The article considers both domestic and foreign scientific studies, which highlight various aspects of the influence of reactive oxygen and nitrogen species, as well as other free radicals on the formation of oxidative stress in pathological conditions that are part of the metabolic syndrome complex. This describes the mechanisms of the formation of chronic inflammation through excessive secretion of pro-inflammatory cytokines and adipokines, activation of the transcription factor NF-kB, as well as damage to the antioxidant system in obesity. Separately, a number of mechanisms of the stimulating effect of adipokines: leptin, adiponectin, chimerine, omentin 1, resistin, on the formation of oxidative stress have been noted. The ways of activating the polyol pathway, as well as diacyl-glycerol — protein kinase C — the signaling pathway of oxidative stress, the formation of mitochondrial dysfunction is described. As a result of which there is an excessive production of free radicals in insulin resistance, diabetes mellitus and macroand microvascular complications of diabetes. In addition, the influence of oxidative stress directly on the formation of cardiovascular diseases of atherosclerotic genesis, as well as arterial hypertension, has been shown.

The article presents data of the influence of cytokines of different directions of glucose and lipid metabolism in obesity. A change of the basic paradigm regarding adipose tissue has contributed to a number of recent discoveries. This concerns such basic concepts as healthy and diseased adipocytes, and, as a consequence, changes of their metabolism under the influence of cytokins. Distinguishing the concept of organokines demonstrates that despite the common features of cytokine regulation, each organ has its own specifics features of cytokine regulation, each organ has its own specific an important section of this concept is the idea of the heterogeneity of adipose tissue. Knowledge of the function of adipose tissue localized in different compartments of the body is expanding. There are date about the possibility of transition of one type of adipose tissue to another. A possible mechanism linking adipose tissue inflammation and the formation of insulin resistance (IR) is presented in this paper. The mechanism of IR development is closely connected with to proinflammatory cytokins disordering the insulin signal, accompanied by a decrease of the work of glucose transporters. A decrease of the income of glucose into cells leads to a change of glycolysis level to an increase of the fatty acids oxidation. Cytokins are able to participate in the process of the collaboration of some cells with others, that occurs both during physiological and pathological process.

There is a great worldwide trend in the incidence of obesity, which is increasing with each passing year among all populations, including women of reproductive age. Given the impressive list of diseases associated with obesity, as well as the negative inverse correlation of the severity of obesity with fertility, this problem is global not only in the social sphere, but it also becomes demographically significant.

Along with other pathogenetic mechanisms leading to persistent anovulation, an imbalance in adipokine production by adipose tissue can also serve as one of the important links in the development of reproductive dysfunction. Despite apparent interest in this topic, a large number of previously discovered adipokines are still not studied. Among adipokines, the effects of adiponectin and leptin on reproductive function are best known. Alterations in adiponectin and leptin levels can affect hypothalamic-pituitary-gonadal signaling, folliculogenesis, oogenesis and steroidogenesis. In addition, leptin is involved in the initiation of puberty, regulation of the menstrual cycle, and changes the balance between proliferation and apoptosis in ovarian cells. The leading causes of reduced fertility, infertility, and IVF failure in obese patients are mechanisms that promote the formation of chronic anovulation, delay the maturation of oocytes, reduce their quality, and/or lead to changes in endometrial susceptibility. These effects can be caused by an imbalance in the concentrations of leptin and adiponectin (leptin excess and adiponectin deficiency), lead to endometrial dysfunction, disruption of implantation and early embryogenesis. These changes, in turn, can affect just as the likelihood of spontaneous conception, so the effectiveness of assisted reproductive technologies and subsequent gestation.

Thus, the study of potential pathogenetic pathways of fertility regulation in obesity, one of which is the subject of this review, is an important area for further study.

Irisin is a polypeptide hormone of muscle tissue (myokine), the synthesis and secretion of which increase against the background of physical exertion, which plays a significant role in the metabolism of fat, muscle and bone tissues. It is known that irisin promotes the transformation of white adipose tissue into brown adipose tissue. It has also been experimentally proven that the introduction of irisin contributed to an increase in bone mass and the prevention of osteoporosis and muscular atrophy. There are works indicating a positive effect of irisin in the functioning of bone, fat and muscle tissues in humans. Diabetes mellitus (DM) is an independent risk factor for osteoporotic fractures and the development of specific diabetic myopathy, at the cellular level similar to the aging of muscle tissue, and type 2 diabetes is also associated with the presence of obesity. Thus, it is of particular interest to study the effect of irisin on the state of bone, muscle and adipose tissues and glucose homeostasis in patients with diabetes. This literature review highlights the biological functions of irisin in healthy people and patients with DM.

Water balance in the body is achieved by balancing renal and non-renal water losses with corresponding water intake. It is under the control of both the central nervous system, which integrates many parameters of water and electrolyte balance in the body, including inducing important adaptive behavioral responses, and three hormonal systems: vasopressinergic, renin-angiotensin-aldosterone and apelinergic. A lot of research is devoted to the regulation of water-electrolyte metabolism. However, this process is still quite difficult to understand, especially since more and more of its regulators are being discovered over time. One of them is the hormone apelin, an endogenous ligand for the APJ receptor. As is known, the receptor is highly expressed in many organs, such as the brain, heart, liver and kidneys, lungs, and has multidirectional effects.

This literature review discusses the main characteristics and features of the regulation of these systems in relation to water-electrolyte metabolism, as well as issues of intersystem interaction and modulation of the effects of apelin.

Gout is a disease characterized by deposition of sodium monourate crystals in tissues which is the reason of inflammation among persons with hyperuricemia (HU). The prevalence of HU, which can be considered the first stage of gout formation, varies in different countries. Despite this, only a small number of persons with HU have been shown to develop symptoms of gout. Recent data suggest that HU is an independent risk factor for cartilage and bone damage. UA, both in the form of crystals and in a dissolved form, activates damage and potentiates cell death by releasing reactive oxygen species, activating the necroptosis pathway, neutrophil traps, synthesis of pro-inflammatory cytokines, and other pathogenetic mechanisms that cause the negative effects of HU and gout on articular cartilage and subchondral bone. The association of HU and osteoarthritis (OA) is well known and based on the common pathogenesis, but the direction of this relationship is still a debatable issue. The accumulated data suggest the need for a deeper study of the relationship of gout and asymptomatic HU with pathological processes leading to the development and progression of OA and disorders of bone metabolism.