The level of ROS (fluorescent probe 2’,7’-dichlorodihydrofluorescein diacetate) and lipid content (fluorescent lipophilic dye Nile Red) in the peripheral blood monocyte fraction from patients with type 1 diabetes mellitus and healthy volunteers were assessed by flow cytofluorimetry. The number of CD36+ monocytes was assessed using specific antibodies. In patients with type 1 diabetes mellitus, the levels of ROS and intracellular lipids in monocytes and the number of cells expressing CD36 fatty acid translocase were elevated. These results indicate metabolic changes in the peripheral blood cells of patients with carbohydrate metabolism disorders and can be considered as possible prognostic markers for the development of type 1 diabetes mellitus complications.

INTRODUCTION: The development of iron overload syndrome may be due to both hereditary and acquired factors. The danger of this condition is manifested in the irreversible loss of parenchymatous pool as a result of cirrhotic transformation and marked fibrosis, caused by the consequent accumulation of iron complexes, of such important internal organs as the liver and heart. The amount of iron in the body is assessed by detecting serum ferritin concentration or by measuring liver and heart iron concentration by biopsy (LIC — liver iron concentration; HIC — heart iron concentration). Insufficient diagnostic significance of the serum ferritin concentration criterion, as well as the invasiveness and traumatization of biopsies, are limitations to the widespread use of these methods. OBJECTIVE: The purpose of this review is to present the main etio-pathogenetic factors of iron overload, the impact of this metabolic disorder on the body, and to reflect the basic principles of diagnosis and the leading role of quantitative MRI in the assessment of iron overload of vital internal organs. MATERIALS AND METHODS: Performed literature search in Russian and English languages for the period from 2001 to 2022 years in Medline/PubMed, RINC/Elibrary, CyberLeninka, Google Scholar databases by keywords: iron overload syndrome, liver, liver cirrhosis, ferritin, hemosiderin, MR diagnostics iron overload, MR relaxometry, R2*/T2*, thesaurismoses, magnetic resonance tomography, SIR (signal intensity ratio), LIC (liver iron concentration), biopsy, chronic diffuse liver diseases, DIOS. RESULTS: The final analysis included 27 publications devoted to various etio-pathogenetic aspects of iron overload syndrome. The forms of iron complexes residence in liver parenchymatous tissue are presented. Characteristics of MR-signal behavior depending on the severity of inhomogeneity of the magnetic field created by iron complexes are characterized. The areas of application of magnetic resonance imaging scanning modes for detection and quantitative diagnostics of iron overload are reflected. CONCLUSION: The ferritin-iron complex, also called ferrihydride, has high paramagnetic properties that provide high contrast MR images in the state of tissue iron overload. The leading methods for quantitative assessment of iron overload are the signal intensity ratio (SIR) method and T2*/R2*-relaxometry. Advantages and disadvantages of these methods, consisting in the limits of determining the degree of overload, make it possible to cover a wide range of overload values by complementing each other. Also the influence of parenchyma architectonics disturbances and concomitant accumulation diseases contribute to the formation of diagnostic inaccuracies. Therefore, the development of complex qualitative-quantitative MR diagnostics in order to isolate highly selective biomarkers will play an important role in MR diagnostics of iron overload syndrome.

Aim: to assess the dynamics of laboratory parameters (total calcium, inorganic phosphorus, albumin, and alkaline phosphatase levels) and parathyroid hormone (PTH) concentrations after administrating local injections of vitamin D receptor activators into the parathyroid glands of patients with secondary hyperparathyroidism in chronic kidney disease. The intial PTH concentration ranged from 300 to 600 pg/ml. This range was chosen to explore a more active strategy for managing the disease at its early stages and preventing the induction and progression of cardiovascular complications associated with secondary hyperparathyroidism.Methods: the study included 48 patients diagnosed with end-stage of chronic kidney disease, who were treated in the nephrology and dialysis department. The main group consisted of 34 patients who received two consecutive injections of a vitamin D receptor activator (Paricalcitol) into the most enlarged and technically accessible parathyroid gland under ultrasound guidance. The control group included 14 patients who continued with conservative treatment due to technical infeasibility of performing the injections. Effectiveness was assessed by comparing laboratory parameters before the intervention and six months after the injections in the main group, and among patients continuing standard medical therapy for secondary hyperparathyroidism.Results: the results showed a statistically significant reduction in parathyroid hormone levels after 3 and 6 months of treatment. In the control group, which continued to receive standard drug therapy, PTH and blood phosphate levels continued to rise. No undesirable effects or complications, such as hypocalcemia, bleeding, allergic reactions, and recurrent laryngeal nerve paralysis, were not observed throughout the observation period.Conclusion: this research confirms the efficacy of local injections of vitamin D receptor activators (Paricalcitol) in reducing PTH levels without significant complications or changes in calcium levels. This method could be employed to correct and prevent secondary hyperparathyroidism complications in early stages among patients with end-stage chronic kidney disease, offering a safer and more effective treatment option.

In this review, information is presented within the triad: obstructive sleep apnea/hypopnea syndrome (OSA), glycemic variability, and cardiac arrhythmias in patients with type 2 diabetes mellitus (DM2). Epidemiological aspects, pathogenetic relationships, possible instrumental and laboratory diagnostic methods, as well as approaches to personalized therapy are analyzed. Research is being actively conducted in certain areas of the designated triad, however, no studies have been found that include simultaneous monitoring of indicators reflecting these disorders in patients with DM2. Many issues are still controversial. Sleep disturbances in patients with DM2 are actively studied, but more often questionnaires are used for diagnosis, rather than instrumental methods. There is insufficient data examining the effect of hypoxia on the progression of complications in patients with DM2. Rhythm disturbances are being actively studied in patients with DM2 in combination with various cardiological problems. Of greatest interest is the study of rhythm disturbances in patients with DM2 without concomitant comorbid conditions of the cardiovascular system, in order to identify early signs of diabetic cardiovascular autonomic neuropathy and cardiomyopathy, as well as additional early risk factors for the development and progression of cardiovascular diseases. Most of the studies are devoted to the study of the association of OSA and various arrhythmias in cardiac patients. However, there is no data on the combined effect of glycemic variability and OSA on the development of cardiac arrhythmias in patients with DM2. Additional studies are needed to identify the features of the effect of OSA on cardiac arrhythmias in patients with DM2.

AIM: To evaluate the impact a fixed-ratio combination of insulin glargine(100U/ml) and lixisenatide(iGlarLixi) on the glycemic control in Russian study T2D population uncontrolled on OAD ± insulin therapy in real-world settings.MATERIALS AND METHODS: The Russian subanalysis of international, multicentre, prospective, observational SUCCESS study included 160 T2DM patients who had initiated iGlarLixi within 1 month prior to study inclusion from 11 regions of the Russian Federation. The primary endpoint — HbA1c change from baseline to month 6. Secondary endpoints: HbA1c change after 12 months, achievement of target HbA1c levels after 6 and 12 months; change in FPG and PPG, change in body weight after 6 and 12 months, iGlarLixi dose dynamics. Safety endpoints: adverse events, serious adverse events, adverse events of special interest, frequency of hypoglycemia during the study period.RESULTS: The average age of patients in the Russian population was 60.8±9.4 years; average duration of T2DM was 11.4 years, mean HbA1c — 9.3±1.5%; mean BMI 33.3 kg/m2. Prior to the study, most patients were on 2 (36.3%) and 3 OADs (27.5%), 32.5% — on insulin therapy. The mean change of HbA1c at month 6 was -1.81%, and -2.03% at month 12. 51.3% patients achieved individual HbA1c targets at month 12, 46.7% of patients achieved the HbA1c target without hypoglycemia and weight gain. The decrease of body weight in 12 months was -3.3±4.4 kg. During the study period, 17 cases of hypoglycemia were recorded (0.11 events per patient-year); 1 severe hypoglycemia (0.01 events per patient-year). The total number of adverse events (AEs) was 43(26.9%), serious AEs - 10 (6.3%).CONCLUSION: According to the results of this prospective real world sub-group analysis, initiation of iGlarLixi in Russian adults with T2DM uncontrolled on OADs ± insulin significantly improves glycemic control with low risk of hypoglycemia and no body weight increase.

Сахарный диабет — это заболевание, для лечения которого в большинстве случаев требуется назначение комбинации гипогликемических лекарственных средств. Одной из часто назначаемых комбинаций является сочетание ингибиторов натрий-глюкозного ко-транспортера (SGLT-2) с метформином. Эти препараты оказывают различное влияние на метаболизм углеводов и жирных кислот и обладают редким, но опасным побочным эффектом в виде метаболического ацидоза, механизм возникновения которого и лабораторные маркеры различаются. При приеме метформина возникает риск лактацидоза, а при применении SGLT-2 возможно возникновение эугликемического кетоацидоза. В клинической практике отмечается учащение случаев метаболического ацидоза при совместном применении метформина и ингибиторов SGLT-2 у пациентов с хронической болезнью почек. В статье рассмотрены механизмы действия ингибиторов SGLT-2 и метформина на липидный и углеводный обмен, соотношение эффектов при совместном приеме данных препаратов, а также их роль в развитии ацидотических состояний у пациентов без- и с хронической болезнью почек при монотерапии и при комбинированной терапии данными группами препаратов.

Disorders of calcium and phosphorus metabolism can cause severe complications that require changing of therapeutic strategies and a long treatment in a hospital. The prevalence of diseases accompanied by calcium metabolism disorders varies from low to moderate. For example, primary hyperparathyroidism, as one of the most common causes of pathological changes in calcium metabolism due to parathyroid hormone hypersecretion, occurs with a frequency of 85 to 233 cases per 100 thousand people. In countries where blood calcium measurements are not routinely carried out, this disease and similar conditions are diagnosed less frequently, and at later stages, with a predominance of manifest and complicated forms. However, calcium metabolism disorders require timely detection and correction in order to prevent complications. At the same time, in a number of clinical situations, standard laboratory analysis is not the optimal diagnostic option due to the duration and complexity of its implementation. In particular, the development of acute hyper- and hypocalcemia requires faster obtaining of blood test results. It is promising to apply technologies allowing to quick assess the current level of calcium directly at a doctor's appointment especially in cases of drug doses adjustment for patients with chronic disorders of calcium metabolism. In this regard, when long-term monitoring of calcemia is required or in emergency situations, the potential benefit can be obtained by using portable Point-of-Care (POC) devices or wearable biosensors. This review examines the clinical and methodological aspects of monitoring calcium levels, their capabilities and practical limitations, and also highlights the prospects for the development and implementation of POC devices and biosensors for ionized calcium.

Background: Hyperferritinemia associated with obesity and insulin resistance is a link between the components of the metabolic syndrome and a possible triggering factor in the pathogenesis of carbohydrate metabolism disorders and dyslipidemia.Aim: To establish possible relationships between ferrokinetic parameters, parameters of lipid and carbohydrate metabolism in overweight and obese patients, and to analyze the possibility of using iron metabolism parameters (ferritin and serum iron) as predictors of carbohydrate metabolism disorders in this cohort of patients.Material and Methods. The study included 52 overweight or obese patients. In the course of the study, patients were stratified into groups depending on the presence of carbohydrate metabolism disorders (CMD), and depending on the state of iron metabolism. Among all patients included in the study, an assessment of anthropometric data, a study of glycated hemoglobin, a standard glucose tolerance test with 75 g of glucose, a study of hematological parameters, as well as biochemical parameters of iron metabolism – the concentration of serum iron, transferrin and ferritin, was carried out.Results. Patients with CMD – impaired glucose tolerance or impaired fasting glycaemia – had significantly higher serum ferritin levels than obese patients without CMD (p = 0.019). In persons with a high level of ferritin, CMD developed significantly more often than in patients with a ferritin content in the range below the 75th percentile (χ2 = 5.278, p = 0.022). According to the ROC analysis, ferritin showed a rather high sensitivity – 75%, and specificity – 84.4% at a diagnostic threshold of 126.65 ng/ml (area under the curve = 0.738; p = 0.016) in the diagnosis of prediabetes (IGT/IFG) in overweight and obese individuals.Conclusion. High concentrations of iron and ferritin are positively associated with CMD, with ferritin being a promising predictor of prediabetes and type 2 diabetes mellitus.

The purpose of the study was to evaluate the severity of changes in the values of markers-candidates for the differential diagnosis of anemia of chronic diseases in patients with type 1 and type 2 diabetes mellitus. The total number of leukocytes, erythrocyte sedimentation rate, content of C-reactive protein, TNFa, ferritin and hepcidin were evaluated. 50 people with type 1 diabetes mellitus and 81 people with type 2 diabetes mellitus were examined. The diagnosis of anemia was established on the basis of data on the level of hemoglobin, the content of erythrocytes in the blood, ferritin and serum iron. Next, the type of anemic syndrome was determined. The patients were divided into groups: 14 patients with diabetes mellitus and anemia of chronic diseases, 15 people with diabetes mellitus and iron deficiency anemia, 38 patients with diabetes with latent iron deficiency and 64 patients with diabetes mellitus without anemia. The comparison group consisted of 17 healthy volunteers. It was shown that in the general sample of patients with diabetes mellitus anemia of chronic diseases was distinguished only by the erythrocyte sedimentation rate, which was higher than in iron deficiency anemia, latent iron deficiency and in patients without anemia. The severity of inflammation in diabetic patients was analyzed depending on its type. The concentration of hepcidin in the blood of diabetic patients, regardless of type, exceeded its content in the blood of healthy individuals. Elevated serum concentrations of TNFα were characteristic of inflammation in type 1 diabetes mellitus. Diabetes mellitus type 2 was characterized by an increase in: erythrocyte sedimentation rate - relatively healthy individuals; concentrations of C-reactive protein - in comparison with healthy volunteers and patients with type 1 diabetes mellitus; ferritin levels compared with patients with type 1 diabetes mellitus. Taking into account the type of diabetes and the type of iron metabolism disorder, it was found that in type 1 and type 2 diabetes mellitus, only the erythrocyte sedimentation rate in patients with anemia of chronic diseases was significantly higher than in patients with iron deficiency anemia and without anemia. The article discusses the reasons for the difficulties in using inflammatory markers (ferritin and hepcidin) as parameters for verifying anemia of chronic diseases in patients with diabetes mellitus. It is pointed out that it is necessary to take into account the differences in the mechanisms of inflammation development in type 1 or type 2 diabetes mellitus when trying to use cytokines and C-reactive protein as additional diagnostic markers in practice. The rationale is given for the prospects of determining the erythrocyte sedimentation rate, with the recommendation of a certain threshold value, for the detection of anemia of chronic diseases in patients with type 1 and type 2 diabetes mellitus.

For clinical medicine the problem of complications associated with the metabolic syndrome is significant and requires a multidisciplinary approach, since the metabolic syndrome itself has long since moved from the sphere of interest of endocrinologists and cardiologists to general medical practice. Most commonly, the metabolic syndrome leads to cardiovascular and cerebrovascular complications. One of the topics currently under discussion is the question of the influence of the components of the metabolic syndrome on the condition of the respiratory system. An epidemiological association between visceral obesity and insulin resistance with chronic obstructive pulmonary disease, bronchial asthma, and obstructive sleep apnea/hypopnea syndrome has been established. Although respiratory disorders are common in patients with clinical equivalents of the metabolic syndrome, their pathogenesis is not well understood. Aim of the study was to analyze the role of individual most significant components (pathogenetic factors) of the metabolic syndrome in the pathogenesis of respiratory disorders. Conclusion . Clinical and laboratory equivalents of the metabolic syndrome, such as obesity, hyperglycemia, and hyperinsulinemia, contribute to respiratory function impairment. The most discussed process that combines the components of the metabolic syndrome and its associated complications is chronic systemic inflammation. The review presents a conceptual scheme of the pathogenesis of respiratory disease in the metabolic syndrome and highlights the role of its factors in the development of qualitative changes in the air-blood barrier and a decrease in the diffusion capacity of the lungs. The authors pointed out a number of unresolved issues in the pathogenesis of respiratory disorders in the metabolic syndrome and also emphasized the relevance of experimental studies of early mechanisms of lung disease development using animal models.

Type 1 diabetes mellitus was modeled in Wistar rats by intraperitoneal injection of streptozotocin (25 mg/kg for 5 days), which led to the appearance of the main symptoms of insulin-dependent diabetes. In peripheral blood mononuclear cells isolated by centrifugation on a Ficoll density gradient, the production of ROS and the level of intracellular lipids were evaluated by flow cytofluorimetry. In rats with type 1 diabetes mellitus, an increase in ROS levels in isolated peripheral blood monocytes, but not in the lymphocytic fraction was revealed. Incubation of isolated monocytes in a medium containing 1 mM oleic acid led to a 1.5-fold increase of intracellular lipid levels. After incubation of the lymphocyte fraction in this medium, no differences from the control were revealed. Disorders of carbohydrate and lipid metabolism in type 1 diabetes mellitus leading to an increase of free fatty acids and ROS levels can be detected ex vivo in isolated peripheral blood mononuclear cells.

Objective: identify differences or comparability of constitutional-morphological characteristics and indicators of the fatty constitution between patients with schizophrenia and people with MetS and without mental disorders. Materials and methods. We examined 63 patients with schizophrenia and MetS (25 women, 38 men), aged 30 [33;52], and 50 mentally healthy individuals with MetS (28 women, 22 men) aged 57 [49; 60]. The main criterion for inclusion in the study was the presence of a verified MetS according to the criteria of the International Diabetes Federation. Anthropometric examination was performed according to the method of V.V. Bunak (1941) with the underlying calculation of integral indices. The determination of the fat component included: measuring waist circumference; non-invasive bioimpedancemetry – body weight, BMI, total and visceral fat content; determination of the total fat fold (electronic caliper). In the blood serum, the concentration of glucose, total cholesterol, HDL, TG was determined using standard commercial kits, the calculation of LDL and the Atherogenic Index. Results. Differences in the prevalence of the constitutional-morphological type and the type of somatic sexual differentiation were not established in the groups. The level of visceral fat and BMI were higher in mentally healthy individuals with MetS than in schizophrenic patients with MetS ( p = 0.005 and p = 0.0001, respectively). Patients with schizophrenia and MetS had low serum glucose levels compared with individuals without mental disorders ( p = 0.0001). An increase in the level of TG and the Atherogenic Index was found in patients with schizophrenia with MetS ( p = 0.026 and p = 0.03, respectively), and the level of HDL was reduced ( p = 0.022). Conclusion. The constitutional and morphological basis of MetS in patients with schizophrenia and persons without mental disorders is the same, however, changes in the fat constitution were determined for mentally healthy individuals. Changes in the lipid profile and glucose concentration may be associated with the presence of MetS-specific risk factors for patients with schizophrenia.

Obesity is considered as a chronic progressive disease, heterogeneous in its etiology and clinical manifestations, and characterized by excess in body fat mass and its deposition in the body. The term “morbid obesity” refers to excessive deposition of adipose tissue with a body mass index (BMI) ≥40 kg / m 2 or with a BMI ≥ 35 kg / m 2 in the presence of serious complications associated with obesity. Along with obesity, the frequency of type 2 diabetes mellitus and cardiovascular diseases closely associated with it has increased. It results from the progression of metabolic disorders, including insulin resistance, which is inextricably linked with the accumulation of visceral fat and plays a key role in the pathogenesis of obesity-related diseases. The study of lipidomic signatures in obesity and associated conditions is a promising branch of fundamental medicine, which makes it possible to significantly and at a new conceptual level stratify a cohort of obese patients into various phenotypes, including a metabolically healthy and metabolically unhealthy obesity phenotypes. Dynamic changes in the lipidome both in the context of diet, drug treatment, and after various bariatric surgeries are of great interest for developing personalized strategies for the treatment of this disease. Currently available studies and their results suggest that we are only at the very start of studying this promising biomedical field.

Iron affects the pathogenesis and clinical course of several chronic metabolic diseases such as obesity, atherosclerosis, non-alcoholic fatty liver disease and type 2 diabetes mellitus. High pro-oxidant iron activity is physiologically controlled by mechanisms regulating entry, recycling, and loss of body iron. These mechanisms include the interplay of iron with ferritin, transferrin, hepcidin, insulin, as well as with adipokines and proinflammatory molecules. An imbalance of these regulatory mechanisms results in both systemic and parenchymal siderosis. Iron overload has a toxic effect on the major tissues involved in lipid and glucose metabolism — pancreatic β cells, liver, muscle, and adipose tissue — as well as the organs affected by chronic hyperglycemia — brain, retina and kidneys. Hyperferremia leads to a decrease in insulin secretion, the formation of insulin resistance and increased liver gluconeogenesis. Molecular mechanisms for these effects are diverse. Elucidating them will implicate both for carbohydrate metabolism disorders prevention and for the pathogenesis of other diseases that are, like diabetes mellitus type 2, associated with nutrition, aging and iron. The literature review presents data from world studies on the mutual influence of glucose metabolism and iron overload, and discusses the differences between hereditary and acquired disorders of iron metabolism from the standpoint of their influence on carbohydrate metabolism.

There is a universal trend towards increase of patients with chronic kidney disease by 7% on average. In the Russian Federation, the annual increase is even higher, at about 10%. The average age of patients receiving renal replacement therapy is 60 years in the Tomsk region and 56 years in Russia, which is relatively lower than in European countries and the United States. With increasing age of patients receiving dialysis treatment, a progressive increase in the incidence of secondary hyperparathyroidism is recorded. Mineral and bone disorders, hyperphosphatemia, hypercalcemia all lead to premature vascular calcification, increase the risk of cardiovascular complications and death. At the same time, elderly patients are characterized by an increase in risks immediately after the start of dialysis therapy. There is a global tendency towards increase in the target level of parathyroid hormone. Parathyroidectomy is recognized as a gold standard for treatment of drug-resistant hyperparathyroidism across the world. As the development of hyperplasia in the parathyroid glands does not proceed synchronously, instead progressing at different rates and in the selective glands, methods of local influence on the altered glands have recently been developed in order to gradually control secondary hyperparathyroidism. Alternative to the total parathyroidectomy are minimally invasive non-surgical methods, attractive due to a smaller number of complications, such as bleeding and paresis of the recurrent laryngeal nerve. Examples of minimally invasive methods are local injections of preparations of the active form of vitamin D, which lead to apoptosis of parathyroid gland cells instead of their destruction, and are safer in relation to surrounding tissues. This article presents current data on the prevalence of secondary hyperparathyroidism in chronic kidney disease. An analysis of clinical trials was carried out based on articles indexed in the Scopus database, the Russian Science Citation Index, PubMed and Web of Science.

The problem of the relationship of nutritional status with the risk of development, course features and prognosis of chronic obstructive pulmonary disease is of considerable scientific and practical interest, but remains poorly understood. However, in clinical practice, it is customary to calculate only the body mass index, but this indicator cannot provide a complete characterization of the nutritional status. We have reviewed the data of publications indicating the conditionality of the course of chronic obstructive pulmonary disease by the value of the body mass index, the amount of muscle mass of the body and such parameters of adipose tissue as its distribution in the body, hormonal activity and production of systemic chronic inflammation markers. To assess the dynamics of body mass index and spirometric parameters in patients with chronic obstructive pulmonary disease, 76 publications that were selected by the keywords COPD, BMI in the Scopus, PubMed, eLibrary databases for 19952022, were analyzed. Correlation analysis was carried out using Spearman's test. As a result, there was a trend towards an increase in body mass index in patients with chronic obstructive pulmonary disease in different countries and an improvement in spirographic parameters in a cohort of patients with chronic obstructive pulmonary disease over time. The data of the reviewed studies indicate the presence of a relationship between chronic obstructive pulmonary disease and nutritional status. At the same time, the mechanisms of the relationship between the pathogenesis of chronic obstructive pulmonary disease and adipose tissue dysfunction, as well as the role of adipose tissue and body composition in the course of the disease and its prognosis, have not been sufficiently studied.