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BACKGROUND: To date, the results of Metformin, Gosogliptin and combination thereof have not been studied on a large patient population with type 2 diabetes mellitus (DM2), including comorbid patients, in real clinical settings in the Russian Federation.AIM: The aim is to evaluate the efficacy, safety, treatment adherence and satisfaction of patients with DM2 with the use of Metformin and Gosogliptin sugar-lowering drugs and combination thereof in routine clinical practice.MATERIALS AND METHODS: The nationwide PALITRA multicenter observational study was conducted among patients with DM2 who were prescribed therapy with Metformin or Gosogliptin or combination thereof in everyday clinical practice. Groups were formed according to the sugar-lowering drug administered; a total of 5741 patients aged 18 to 65 years with DM2 and a wide comorbidity profile participated. The observation period was 6 months. Body weight, body mass index (BMI), blood pressure (BP), glycated hemoglobin (HbA1c) level, glycemic parameters, and biochemical parameters (ALT, AST and plasma creatinine) were recorded initially and 3 and 6 months after the initiation of therapy with the study drugs. Adherence to therapy and patient and physician satisfaction with the treatment were assessed using Likert scale.RESULTS: HbA1c level decreased by 1.03% in the Metformin monotherapy group and by 0.95% in the Gosogliptin monotherapy and Metformin and Gosogliptin combination therapy groups by Week 24. By the end of the study, 49.6% of patients with DM2 reached the target HbA1c level (

Due to its effect on insulin resistance, ease of administration and favorable safety profile, metformin has been included in the recommendations of foreign medical communities for the management of pregnant women with hyperglycemia since 2008. However, in Russia, the use of any oral hypoglycemic agents during pregnancy is still contraindicated. However, recent studies demonstrate the safety and positive effects of metformin on pregnancy in patients with pregestational diabetes mellitus, polycystic ovary syndrome and gestational diabetes mellitus. In 2023, the Federal Service for Surveillance in Healthcare of the Ministry of Health of Russia updated the instructions for the medical use of Glucophage® and Glucophage®Long: pregnancy was excluded from the “Contraindications” section and moved to the “With caution” section. This resolution is intended to evaluate studies of the effectiveness and safety of metformin, as well as to study the experience of foreign colleagues and Russian legal aspects of prescribing metformin in the stages of preparation for pregnancy, during it and in the post-gravid period.

On March 20, 2024, an interdisciplinary meeting of the Expert Council on the current problem of B12 insufficiency/deficiency and the prevalence of this condition among endocrine patients was held at the Endocrinology Research Centre (Moscow). The purpose of the meeting was to assess the role of B12 deficiency in reducing the quality of life of patients of different groups and to outline a strategy for the management of patients with vitamin B12 insufficiency/deficiency by endocrinologists.The resolution of the expert council was developed by leading specialists in various specialties.

An erratum on « Insufficiency/deficiency of vitamin B12 in patients in the endocrinological practice» by Natalya G. Mokrysheva, Marina V. Shestakova, Alexander S. Ametov, Mikhail B. Antsiferov, Igor G. Bakulin, Tatiana V. Vavilova, Gagik R. Galstyan, Tatiana Y. Demidova, Fatima K. Dzgoeva, Tatiana L. Karonova, Elena A. Lukina, Ashot M. Mkrtumyan, Rodion V. Ponomaryov, Natalia A. Suponeva, Olga Y. Sukhareva, Minara S. Shamkhalova (2024). Diabetes mellitus. 27(3). doi: 10.14341/DM13181An error was made in the list of authors: Nina A. Petunina was not indicated as author of this article. The correct list of authors: Natalya G. Mokrysheva, Marina V. Shestakova, Alexander S. Ametov, Mikhail B. Antsiferov, Igor G. Bakulin, Tatiana V. Vavilova, Gagik R. Galstyan, Tatiana Y. Demidova, Fatima K. Dzgoeva, Tatiana L. Karonova, Elena A. Lukina, Ashot M. Mkrtumyan, Nina A. Petunina, Rodion V. Ponomaryov, Natalia A. Suponeva, Olga Y. Sukhareva, Minara S. Shamkhalova.The identifier in the ORCID system for F.K. Dzgoeva was also indicated incorrectly. The correct link is: https://orcid.org/0000-0002-0533-7652.The editorial board apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.

Metformin is a sugar-lowering drug that is actively used in long-term therapy of type 2 diabetes mellitus (DM2). The safety of metformin for different groups of DM2 patients is currently well studied. However, the drug is contraindicated for patients with severe renal impairment and should be used with caution in cases of moderate renal impairment. Since contrast agents as well as metformin are excreted by kidneys, patients with reduced renal function taking metformin require special attention due to the risk of lactic acidosis, a life-threatening condition resulting from functional renal failure and accumulation of metformin in tissues. Numerous studies have shown that the risk of lactic acidosis is relatively low and in most cases is not associated with metformin therapy per se, but rather with comorbidities. Initial versions of clinical recommendations related to the use of contrast agents strictly limited the use of metformin before and after examination, but as data on lactate acidosis and possible causes of this condition expanded, the recommendations gradually became less strict. For emergency contrast studies, they are currently unchanged, but data are gradually accumulating on the safety of continuing metformin in these clinical situations. There is no consensus among contrast manufacturers on whether and in what regimen metformin should be interrupted during contrast studies as well as on a number of other related issues. The best strategy for clinicians is to check the instructions for each specific drug before use.

Patients with type 2 diabetes mellitus (T2DM) are at high risk of adverse outcomes in coronavirus infection (COVID-19). Despite the gradual resolution of the pandemic, new strains of the virus are emerging, characterized by high contagiousness, and the risk of infection becoming a seasonal disease is increasing. In this connection, the issue of identifying risk factors that aggravate the course of COVID-19 in patients with T2DM, including the role of initial hypoglycemic therapy, remains relevant.The review presents and systematizes up-to-date information (according to randomized clinical trials and meta-analyses) on the effect of outpatient and inpatient use of metformin and innovative hypoglycemic drugs (glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors) on the course and outcome of COVID-19 in patients with T2DM. At the same time, the potential mechanisms of the pathogenetic effect of drugs on the course of COVID-19, positive and negative aspects of their administration are described.

In the contemporary reality pharmacological correction of the early carbohydrate metabolism disorders is the main method for the type 2 diabetes prevention. Taking into account the main role of insulin resistance in the prediabetes development it can be supposed that pharmacological agents directly activating the insulin receptor are the pathogenic-base therapy for prediabetes treatment. Such kind of this pathogenic therapy is Subetta® – a representative of the class of biological drugs created using the based graduated technology. Due to the absent of the direct comparative trials of Subetta® versus metformin in the efficacy of the type 2 diabetes prevention in prediabetes patients, was performed an analysis of the effectiveness of these two drugs using the adjusted indirect comparison method of the results of the randomized double-blind placebo-controlled clinical trial of Subetta® efficacy and safety in impaired glucose tolerance patients with the results of several metformin studies similar in inclusion and efficacy criteria. The results indicate greater Subetta® efficacy in the treatment of glucose intolerance and metformin's – in the impaired fasting glucose treatment, which can be explained by the differences in the action mechanisms of these two drugs for prediabetes treatment.

Background. It is known that the protective effect of adaptation and conditioning influence is weakened in animals with metabolic syndrome. Metabolic syndrome may be the basis for the failure of cardioprotection in clinical settings.The aim of the study. To identify the relationship between disorder in carbohydrate and lipid metabolism and a decrease in the effectiveness of the infarct-limiting effect of moderate chronic normobaric hypoxia; to check the possibility of correcting reduced cardioprotection by normalizing carbohydrate and lipid metabolism.Methods. The study included 64 Wistar rats. Metabolic syndrome was induced by feeding animals a high-carbohydrate, high-fat diet for 84 days. Chronic normobaric hypoxia was carried out for 21 days in the following mode: 12 % O2 : 0.3 % CO2. Metformin at a dose of 200 mg/kg/day or PPARα agonist WY14643 at a dose of 1 mg/kg/day were added to the drinking water of rats with metabolic syndrome during adaptation period to hypoxia. A 45-minute coronary occlusion and 120-minute reperfusion were performed, and the infarct size was determined. Indicators of lipid and carbohydrate metabolism, leptin, and adiponectin were studied in the blood serum.Results. The infarct-limiting effect of chronic normobaric hypoxia was weakened in animals with metabolic syndrome. Infarct size showed a direct correlation with decreased glucose tolerance and serum triglyceride levels. Using metformin therapy did not lead to the restoration of the infarct-limiting effect of chronic normobaric hypoxia, while the normalization of lipid metabolism with the use of the PPARα agonist WY14643 corrected the impairment of adaptive cardioprotection in rats with metabolic syndrome.Conclusion. The lack of cardioprotection at chronic normobaric hypoxia in rats with metabolic syndrome is associated with impaired carbohydrate and lipid metabolism. The PPARα agonist restores impaired lipid metabolism and adaptive cardioprotection.

Metformin, known in the medical community as the drug of first choice for type 2 diabetes mellitus, belongs to the group of biguanides and has proven to be an effective treatment in clinical practice. Our knowledge of the pharmacodynamic properties of metformin has long been limited to the following well-known mechanisms: a decrease in hyperglycemia due to an increase in peripheral insulin sensitivity, glucose utilization by cells, inhibition of hepatic gluconeogenesis, an increase in the capacity of all types of membrane glucose transporters, activation of fibrinolysis, and a decrease in the levels of atherogenic lipoproteins. Recent studies show that the range of positive pleiotropic effects of metformin is not limited to the above, and that the molecular mechanisms of its action are more complex than previously thought. This article presents a less known, but equally important action of metformin, in particular, its anti-oncogenic, antiviral, and anti-aging effects. In our study, we highlight that the activation of 5’-adenosine monophosphate-activated protein kinase (AMPK) should be considered as the primary mechanism of action through which almost all beneficial effects are achieved. In the light of recent scientific advances in metformin pharmacology, together with the pathogenetic uncertainty of the term «biguanide», it seems fair and reasonable to apply a more relevant definition to the drugn, namely «AMPK activator».

BACKGROUND: In men, obesity is accompanied by a complex of metabolic and hormonal disorders, which leads to androgen deficiency and impaired spermatogenesis. Antidiabetic drugs, including metformin (MF), and luteinizing hormone receptor (LHR) agonists, which activate testicular steroidogenesis, can be used to correct reproductive dysfunctions. However, in diet-induced obesity (DIO), their effectiveness and mechanisms of action are poorly understood.AIM: In men, obesity is accompanied by a complex of metabolic and hormonal disorders, which leads to androgen deficiency and impaired spermatogenesis. Antidiabetic drugs, including metformin (MF), and luteinizing hormone receptor (LHR) agonists, which activate testicular steroidogenesis, can be used to correct reproductive dysfunctions. However, in dietinduced obesity (DIO), their effectiveness and mechanisms of action are poorly understood.MATERIALS AND METHODS: Obesity in male Wistar rats was induced by a 23-week diet enriched with saturated fats. MF treatment was carried out for 5 weeks at a dose of 120 mg/kg/day (orally), and the treatment with hCG and TP03 was carried out for 5 days at daily doses of 20 IU/rat (s.c.) and 15 mg/kg (i.p.), respectively. Using microscopy and histochemical analysis, the number and motility of spermatozoa (SP), the number of their defective forms and the morphology of the seminiferous tubules were assessed, and the levels of testosterone and other hormones in the blood were measured using ELISA.RESULTS: MF, hCG, and TP03 to varying degrees increased the number of SP and the proportion of their mobile forms, including those with forward movement, which were reduced in DIO rats, and also normalized the thickness of the epithelium of the seminiferous tubules and the number of spermatogonia and pachytene spermatocytes in them, but did not reduced the proportion of defective forms of SP, increased in DIO. In the case of MF, this was associated with the drug-induced normalization of body weight, glucose tolerance, and the insulin and leptin levels in DIO rats. The positive effect of hCG and TP03 on spermatogenesis was due to their stimulating effect on testosterone production.CONCLUSION: The use of long-term MF therapy and short-term courses of LHR-agonists normalizes impaired spermatogenesis in DIO, which indicates the prospects for their use to improve male fertility in obesity, and in the case of MF therapy, normalization of the metabolic and hormonal status is of great importance, while in the case of LHR-agonists the most important factor is their steroidogenic effect.

Introduction and purpose: PCOS is identified by the presence of underdeveloped follicles in the ovaries caused by a lack of ovulation, and it is linked to heightened production of androgens in the ovaries. The observable symptoms of PCOS encompass irregular or absent menstrual cycles, obesity, and indications of excess androgens such as acne or oily skin. Metformin could be advantageous for a specific group of women with PCOS. The aim of this study is to summarize the current knowledge regarding the effectiveness of metformin in the treatment of PCOS based on available scientific literature. A brief description of the state of knowledge: Metformin indirectly aids in enhancing ovulation and alleviating long-term metabolic issues, although its impact is considered moderate. Metformin also diminishes the levels of particular markers linked to arterial issues and chronic inflammation beneath the surface. This indicates a potential decrease in the continual risks of type 2 diabetes (DM) and cardiovascular disease (CVD) for women dealing with PCOS. Summary (conclusions): Managing PCOS involves personalized targets due to its diverse nature. In clinical practice, metformin is a recommended first step for managing PCOS in overweight or obese patients, particularly when oral contraceptives are not suitable or insulin resistance is evident.

BACKGROUND: Since the very first outbreak, scientists have been trying to determine the most critical pathogenetic mechanisms for the development of COVID-19 and related complications, analyze individual subpopulations of patients with chronic diseases and develop optimal tactics to combat not only the infection itself but also its acute and chronic complications.AIM: to assess the COVID-19 course among patients with Type 1 and Type 2 DM.MATERIALS AND METHODS: A retrospective cohort study of Tashkent inhabitants, who had COVID-19 from April to D ecember 2020, was performed. The data were obtained from the single electronic database of registered cases of COVID-19. All data were analyzed using a logistic regression in STATA 17.0 software. Further, the matched case-control study was performed for patients with type 2 DM and no DM based on age, gender, and BMI.RESULTS: Of the 5023 analyzed subjects, 72.63% had no diabetes mellitus (DM), 4.24% had type 1 DM, 15.19% had type 2 DM, and 7.94% was diagnosed with DM during the COVID-19 infection. DM, overweight, and obesity were associated with severe COVID-19; the most significant risk of a severe course was found in persons with type 2 DM. The risk of a lethal outcome and the need for prescription of glucocorticoids did not show a significant association with diabetes in Tashkent. The clinical features of COVID-19 were more common in patients with type 2 DM, especially for shortness of breath, chest pain, and arrhythmia. The persons receiving SU have complained of dyspnea significantly more often than matched patients without DM. Metformin and DPP4i were the groups of drugs that were not associated with significantly increased risk of hospitalization of patients because of COVID-19. The matched case-control study did not reveal statistically significant differences in the disease course severity, need for hospitalization and glucocorticoids, and death depending on the glucose-lowering therapy preceding the onset of COVID-19.CONCLUSION: Diabetes, age and overweight/obesity were associated with severe course of COVID-19 in Tashkent. There was no statistical difference in COVID-19 severity depending on initial glucose-lowering therapy.

BACKGROUND: The information available to date on the effect of metformin on the transcriptome and secretory capacity of adipocytes in human adipose tissue (AT) is scarce and contradictory. The study analyzed whether metformin in vitro modulates gene expression and secretion of adiponectin and leptin in the AT of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) localization of patients with ischemic artery disease (IHD).AIM: To assess the effect of metformin at various concentrations (1 and 10 mmol / L) on the level of expression of adiponectin and leptin genes and their content in adipocytes of subcutaneous, epicardial and perivascular AT of patients with IHD.MATERIALS AND METHODS: The study included 134 patients with IHD and indications for direct myocardial revascularization by coronary artery bypass grafting (CABG). During the operation, biopsies of SAT, EAT and PVAT were obtained for 3–5 gram, which served as a source of adipocytes. Isolated adipocytes were cultured for 24 hours with and without metformin (1 and 10 mmol / L). After a day of incubation, the expression of the ADIPOQ and LEP genes and the level of secretion of adiponectin and leptin in the culture medium of adipocytes were determined. Statistical processing was performed using the GraphPad Prism 6 software package (GraphPad Software, La Jolla, CA, USA) and Statistica software, 6.1 (Dell Software, Inc., Round Rock, TX, USA).RESULTS: The adipocytes of the EAT and PVAT of patients with IHD were characterized by an imbalance in the adipokine system, manifested by a low level of ADIPOQ expression and a high LEP expression in comparison with adipocytes of the SAT. Metformin increased the level of ADIPOQ expression and its secretion by adipocytes regardless of their location, while a low concentration (1 mmol / L) in adipocytes of EAT had a stronger effect compared to 10 mmol / L. Metformin had a multidirectional effect on the level of leptin in adipocytes, which depended on their localization: both in low (1 mmol / L) and high concentrations (10 mmol / L), the drug reduced the level of LEP expression and protein secretion in the culture medium of adipocytes of the SAT. EAT had no significant effect on adipocytes. In PVAT, metformin increased the expression and secretion of leptin regardless of concentration.CONCLUSION: Metformin has a direct effect on adipocytes in SAT, EAT, and PVAT and is able to modulate their activity, which is a promising strategy for maintaining the balance of adipokines in AT, especially epicardial and perivascular localization.

Antipsychotic drugs are widely used for many psychiatric disorders, such as schizophrenia, bipolar affective disorder, delusions and hallucinations due to neurological disorders, depression with severe psychotic symptoms. Metabolic disorders including weight gain, dyslipidemia and hyperglycemia are one of the most common side effects of antipsychotic therapy. Psychiatric patients have higher risk of cardiovascular disease, so that the development of metabolic side effects is an important clinical problem that should be solved. Antipsychotic-induced weight gain may cause distress that leads to antipsychotics withdraw and repeated hospitalizations.Lifestyle changes, correction of the antipsychotic treatment, additional medications and their combination are the possible solutions of antipsychotic metabolic side effects. Lifestyle modification is a first-line therapy that should complement other options, when it feasible. At the same time, it can be extremely difficult for patients receiving antipsychotic to adhere dietary and physical activity recommendations. Replacing an antipsychotic with a milder drug is not always possible and may not be enough effective. Metformin seems to be the most well-studied, safe and effective agent that is prescribed to deal with antipsychotic-induced weight gain and associated metabolic disorders. Glucagon-like peptide type 1 receptor agonists and thiazolidinediones are mentioned as alternative medications, but clinical data on their efficacy and safety in this patient group are extremely limited. Dyslipidemia can develop as an independent antipsychotic side effect even without an increase in body weight. The most effective treatment, as in the general population, is statin therapy. However, the joint appointment of statins and antipsychotic significantly increases the risk of adverse reactions, such as myalgia, myopathy, increased creatine kinase levels, due to the competition of drugs for the cytochrome system.It is still unknown what scales should be used for cardiovascular risk stratification in patients taking antipsychotic and whether it is possible to use metformin to prevent antipsychotic-induced weight gain, and if so, how to select patients for whom such therapy can be indicated. Finally, more clinical trials are needed to evaluate the efficacy and safety of other classes of hypoglycemic and lipid-lowering drugs in patients on antipsychotics.

Insulin resistance, which is a fundamental pathogenetic factor of prediabetes, is closely associated with abdominal obesity on the one hand and the development of cardiovascular diseases, heart failure (HF), on the other. The pathogenetic role of insulin resistance is multifaceted and consists in the acceleration of atherosclerosis, the formation of left ventricular myocardial hypertrophy, including through mechanisms that do not depend on blood pressure, as well as the development of its diastolic dysfunction. The latter is the starting point for starting HF with preserved ejection fraction (HFpEF).Compared with patients with HF with reduced ejection fraction, the presence of HFpEF determines a higher frequency of hospitalizations not due to decompensation of heart failure, but due to concomitant diseases, such as destabilization of the course of arterial hypertension, decompensation of type 2 diabetes mellitus, curation of which, in general, has a greater impact in terms of improving prognosis. Thus, in patients with prediabetes and HFpEF, the correction of insulin resistance as the underlying cause and trigger of cardiometabolic disorders can potentially improve not only insulin-glucose homeostasis, but also the parameters of myocardial diastolic function. This literature review is devoted to the accumulated experience of using metformin as a «strategic» antidiabetic drug in HFpEF and considering potential new points of its application as a protector of the cardiovascular system.

This review is devoted to the analysis of data on the study of the possible effect of metformin on the endocrine function of adipose tissue: the synthesis and secretion of adipocyte hormones – adipokines (leptin, adiponectin, resistin) and the gastrointestinal system (ghrelin). metformin is a biguanide class of hypoglycemic drugs used as a first-line therapy for the correction of carbohydrate metabolism. Currently, there has been a significant increase in interest in the pleiotropic cardioprotective and antiatherogenic properties of metformin. The molecular mechanisms of action of metformin on carbohydrate and lipid metabolism in adipose tissue are shown in the example of isolated adipocytes (in vitro) and in a living organism (in vivo). The key enzyme regulation in metformin action is с-AMPactivated protein kinase (AMPK). Activation of this enzyme blocks fatty acid synthesis, activates lipolysis and fatty acid oxidation; inhibits glucose production in the liver, reducing the expression of AMP-stimulated genes of enzymes of gluconeogenesis, increases insulin sensitivity, which ultimately contributes to the reduction of glucose. However, the dose-dependent effects of metformin are not well understood, there is no data on the long-term effects of the drug on the metabolism of adipose tissue, which requires careful attention to the study of this issue. Overall, metformin seems to be a promising drug to combat hyperglycemia, and dyslipidemia in diabetes mellitus type 2 and obesity, and for the prevention of cardiovascular risks associated with these diseases.

Today, prediabetes is regarded by the world medical community as early diabetes mellitus. The accumulated research evidence shows that prediabetes is characterized by a spectrum of complications that are similar to those of diabetes mellitus, which means that the deterioration of cardiovascular prognosis starts already at the stage of prediabetes. In the current timeframe, metformin is actually the only drug that is widely prescribed for the treatment of prediabetes to prevent type 2 diabetes mellitus and cardiovascular diseases associated with insulin resistance and hyperinsulinemia. Meanwhile, metabolically unhealthy obesity characterized by hyperinsulinemia and insulin resistance is associated with a significantly unfavourable course of prediabetes, as well as the highest risk of developing both type 2 diabetes mellitus and cardiovascular diseases, development/ progression of chronic kidney disease. The theme of this review is the priority of metformin for the management of the most prognostically unfavourable phenotypes of prediabetes. The review is also devoted to the description of the most significant mechanisms that provide effects of metformin underlying the management of key disorders that determine the unfavourable prognosis of prediabetes. In particular, it sets forth the role of unhealthy nutrition, its effects on the development of imbalance of the composition of gut microbiota, which, in turn, entails a cascade of metabolic disorders underlying the development of metabolic ill health. The review sets forth the key role of metformin as a drug that protects against the development of these disorders. The information presented in this review will be useful to personalize the choice of both the scope and nature of interventions in patients with different phenotypic characteristics.

Insulin resistance (IR) is an important problem of humanity, which leads to development of many metabolic disorders. Сurrently the pathogenic mechanism of the development of IR is not completely investigated. Nevertheless, there are some hypotheses explaining the development of this condition. These include such hypotheses as the hypothesis of thrifty genotype, thrifty phenotype, hormonal, stress, good and bad calories, chronic metabolic inflammation, microbiotic and integrated model suggested by Professor Rainer Straub. In this article, the microbiotic theory will be considered in detail, explaining the mechanism of the development of peripheral tissue insensitivity to insulin in dysbiosis due to amplification of transmission by proinflammatory molecules from the intestine to the bloodstream and activation of systemic inflammation, disruption of the “gut-brain-periphery” mechanism and impaired receptor interactions of active intestinal metabolites of the gut microbiota (GM) at the level of cells of metabolic organs. The value of this theory is that its factors affect all links in the pathogenesis of the development of IR, reflected in the integrated model of Professor Straub. In this review the influence of GM and metabolic processes of human body on the development of IR will be considered in detail, data from clinical studies about the influence of GM (its composition, active metabolites, individual bacterial strains) on the development of IR and the role of chronic metabolic inflammation in this process will also be presented. In addition, attention will be paid to bidirectional effects of GM and metformin, as well as to data from clinical studies on changes in GM in healthy people and people with IR under the influence of metformin and how GM affects the pharmacokinetics of this drug. The possibility of IR correction through the use of dietary fiber will also be considered.

BACKGROUND: Depending on the polymorphism of genes that that are involved in metabolism, the response of patients to different types of therapy may differ. Despite the potential effect of rs7903146 TCF7L2 and rs1042712 ADRB2 on changes in body composition in different types of therapy of early carbohydrate metabolism disorders, these associations haven’t been studied yet. AIM: To study the influence of rs7903146 TCF7L2, rs1042714 ADRB2 on changes in body fat composition in different types of therapy of early carbohydrate metabolism disorders.MATERIALS AND METHODS: The study involved patients with overweight or obesity and risk factors for Type 2 Diabetes development. All patients underwent genotyping with the real-time polymerase chain reaction, oral glucose tolerance test and bioimpedancemetry. Further, the patients were divided into two groups. First group kept a diet with the exclusion of simple and limitation of complex carbohydrates and fats. Second group took metformin in addition to the diet. Three months after bioimpedancemetry was performed again.RESULTS: The research involved 73 patients (the mean age 48±12 y.o., the mean BMI 34,27±6,18 kg/m2 ). The diet therapy group consisted of 47 people. Other 26 patients took metformin in addition to the diet. In group of diet, T allele carriers of rs7903146 TCF7L2 were characterized with more decrease in fat mass compared with CC homozygotes (- 7.90 ± 9.46% vs. -1.54 ± 8.98%, p = 0.027). CC genotype carriers of rs7903146 TCF7L2 in group of metformin and the diet had a tendency for more decrease in hip circumference compared with T allele carriers (-4.95 ± 3.34% vs. — 2.5 ± 2.96%, p = 0.064). Carriers of C allele in homozygous state of rs1042714 ADRB2, who took metformin with the diet, demonstrated more decrease in hip circumference (- 5.81 ± 3.00% vs. -2.50 ± 2.7%, p = 0.009), the tendency for decrease in fat mass (-8.28 ± 8.86% vs. — 3.20 ± 5.09%, p = 0.068) and waist circumference (-5.91 ± 4.29% vs. -3.03 ± 4.01 %, p = 0.091) compared with G allele carriers. The association of rs7903146 TCF7L2 and rs1042714 ADRB2 with changes in total body weight was not observed (p> 0.05).CONCLUSION: Single nucleotide polymorphisms rs7903146 TCF7L2 and rs1042714 ADRB2 influence on body fat composition in patients with early carbohydrate metabolism disorders in various types of treatment.

Type 2 diabetes mellitus is one of the most important independent risk factors for the development, progression and mortality from cardiovascular diseases (CVD). The world communities are faced with the question of developing the optimal management tactics for such comorbidity patients. Thus, the prescribed drug should not only have an adequate hypoglycemic effect, but also have a number of cardioprotective properties, be safe in patients with CVD, and possibly even improve the prognosis and reduce mortality rates. This review is devoted to a representative of the biguanide class - metformin, which is one of the earliest and most effective antihyperglycemic drugs, both as monotherapy and in combination with other antihyperglycemic drugs and insulin; while the evidence base for its cardiovascular profile is only gaining momentum. Thus, the purpose of this review is to highlight the cardiovascular effects of metformin in the context of recent research.

Metformin is one of the most commonly prescribed drugs for the treatment and prevention of type 2 diabetes mellitus (T2DM). Numerous evidence accumulates indicating that both genetic and environmental factors underlie adverse side effects of metformin, as well as individual differences in patient response to treatment The present review summarizes information on genetic factors and environmental modifiers determining patients’ individual response to metformin treatment. The data on the role of polymorphism of the most significant genes and protein products encoded by them both in the development of adverse effects and in determining the therapeutic response are summarized, and the place of metformin in the realization of the phenotypic effects of these genes is discussed.Endogenous conditions and exogenous effects modifying the response to metformin are considered. Among them are factors that affect the functional state of the genome (the level of methylation of genes, one way or another associated with the response to metformin, etc.), reflecting the biological characteristics of the organism (gender, age), health level (the presence of concomitant diseases, the supply of biometals and vitamins), taking other medications, etc. Thus, there is a wide range of factors modifying the response to metformin, which, unlike genetic characteristics, are largely controllable. At the same time, both genetic and environmental factors may differ in significance in different ethno-territorial groups of the population. This information should be taken into account when developing a personalized approach to prescribing metformin for the treatment of type 2 diabetes, as well as when recommending its use for the treatment of other diseases.

Objective: To study the effect of the rs1801282 PPARG polymorphism on changes in the body composition of patients with early carbohydrate metabolism disorders in groups with different variants of treatment.Materials and Methods: The study involved 64 patients (8 men and 56 women) with early carbohydrate metabolism disorders. At baseline, all patients underwent genotyping for the rs1801282 PPARG polymorphism and body composition determination with bioelectrical impedance analysis (BIA). Then, the patients were divided into two groups depending on the type of therapy. The patients from Group 1 (40 subjects, mean age 45.2±15.4 years) kept a generally accepted diet with the exclusion of simple carbohydrates and limitation of complex carbohydrates and fats. The patients from Group 2 (24 subjects, mean age 51.2±14.5 years) took metformin in addition to the diet therapy. The effects of different types of treatment on body composition changes were assessed with follow-up BIA 3 months after the start of treatment.Results: Carriers of the mutant G allele of rs1801282 PPARG in the metformin and diet therapy group showed a significant increase in the content of body cell mass (1.28±0.51% vs 0.36±0.37%; P = 0.021) compared with CC homozygotes in the absence of differences in body weight changes (P > 0.05).Conclusions: The presence of the mutant allele G of rs1801282 PPARG promotes the increase in body cell mass in case of adding metformin to the diet therapy in patients with early carbohydrate metabolism disorders.

The article is devoted to the actual gynecological problem of women of reproductive age-polycystic ovarian syndrome (PCOS) and the possibilities of its pharmacotherapy. Difficulties in choosing the treatment of the disease are the need to take into account all clinical manifestations, not limited to menstrual disorders and infertility. PCOS is usually accompanied by hirsutism, obesity, decreased glucose tolerance, and other manifestations in various organ systems associated with metabolic disorders. These manifestations significantly reduce the quality of life of patients and also require pharmacological correction. Currently, the first line of drugs in the treatment of PCOS remains combined oral contraceptives, which have been used by women for decades, but, unfortunately, have multiple adverse reactions. The latter is the reason for the search for other methods of pharmacotherapy that are highly effective and safe. Metformin is one these glucose-lowering drugs, which shows effectiveness in the treatment of PCOS. Drugs from such groups as glucagon-like peptide-1 receptor agonists are at the research stage, and the development of treatment tactics using glucose-lowering drugs that have antagonism to glucagon is continuing. Expanding the choice of pharmacotherapy, thanks to the search for new, more effective and safe drugs and combining it with other treatment methods, makes it possible to control PCOS taking into account the individual characteristics of patients.

INTRODUCTION AND PURPOSE: Metformin is one of the most frequently prescribed medications in the whole world. This lipophilic biguanide is widely used as a first-line medicine for patients suffering from type 2 diabetes mellitus because of its high effectiveness in monotherapy, and in connection with other antidiabetic drugs. Glucose-lowering properties of metformin were initially used only in the therapy of type 2 diabetes mellitus, but some data indicate that these properties might state an alternative in the prevention or treatment of some cancers both among diabetic and non-diabetic patients. STATE OF KNOWLEDGE: Metformin molecular mechanisms of action were thoroughly investigated, differentiated, and described, but in the context of the glucose-lowering effect. As a multiway drug, used mainly in diseases characterized by an increased level of glucose in the blood, numerous medical trials were conducted to find other treating properties of metformin. Recently, a few reports presented the potential connection between using metformin in the prevention and treatment of neoplasms in the same mechanisms. The scientists analyzed the influence of metformin’s action on various cancers and drew conclusions. The research on potential anti-cancer features of metformin was conducted for a relatively short period and still presents a challenge to scientists. CONCLUSIONS: The aim of this review is to gather current knowledge and present the latest discoveries about potential anti-cancer features of metformin. We discuss the potential underlying molecular mechanisms of metformin’s action in the human body and indicate the connection between the prevention and treatment of neoplasms. Additionally, we point out the exact cancers in which metformin might play a significant role.

The polycystic ovarian syndrome is an endocrine disorder with a high prevalence affecting reproductive-aged women and adolescent girls. The most common symptoms are infertility, numerous ovarian cysts, hyperandrogenism, menstrual cycle abnormalities. The disease has a great impact on patients, impairing their quality of life. Bearing that in mind, innovative therapeutic approaches are needed. We aim to describe current management and treatment concepts adopted in PCOS therapy. The analysis of previously published studies was conducted by using the PubMed, Google Scholar, and Scopus databases.Mentioned studies show that lifestyle changes may benefit PCOS therapy in multiple ways. Dietary and exercise interventions have a notable influence on women’s body composition as well as biochemical parameters. The reduction of body weight or BMI is a therapeutic achievement likewise patients’ contribution to managing PCOS. Pharmacotherapy provides plentiful treatment choices to adopt. Studies show that hormonal contraceptive has a significant impact on both hyperandrogenism and menstrual abnormalities. Metformin is proven to reduce BMI, improve LDL levels, and lower the risk of OHSS in women undergoing IVF/ICSI-ET. A meta-analysis proved metformin’s monotherapy superiority over clomifene citrate or their combination in treating infertility. However, both substances are not recommended as the first-line choice. Regrettably, many studies mention short of evidence, lack of larger sample sizes, or insufficient duration preventing further research.The conclusion we draw is that approaches of managing and treating PCOS are constantly advancing and updating. However, there is a necessity for future studies to expand their research by gathering more data and considering diverse cases.

Introduction: Life expectancy of human population is being constantly prolonged, hence there is a lot of research into drug that will prevent the effects of aging. There are many reports that metformin, which is a drug used in type 2 diabetes, has anti-aging effects. It belongs to the group of biguanides and has been used since the 1950s. It is a relatively safe, cheap and effective drug, which makes it a promising subject for many studies. The purpose of this review is to present the latest developments in this field. Material and methods: PubMed scientific base was searched using following keywords: metformin, aging, anti-aging, in years 2017-2021. Results: Numerous studies show that metformin has an impact on aging through the nutrient pathway, AMPK signaling pathway, and its effects on reactive oxygen species. In addition, it has an anti-cancer effect, inhibiting, among others, rectal cancer cells and p53 mutant colon cancer. Research in rodents has shown that this drug has anti-aging effects on many organs, including the CNS, ovaries, prostate, heart muscle and skin. Conclusions: Metformin, which is the most commonly used oral drug in type 2 diabetes, has many other mechanisms of action. Its anti-aging effect works on many organs in our bodies, which gives hope to find an anti-aging substance. However, multicentre, randomized trials are needed to determine the exact anti-aging dose, its possible side effects, and effects on various organisms.

In the world, the number of patients with carbohydrate metabolism disorders is steadily growing. Over the past 10 years, the number of patients with diabetes mellitus in the world has more than doubled. Moreover, there is not only an increase in the number of patients with diabetes mellitus, predominantly type 2 diabetes, but also with prediabetes. The term «prediabetes» means impaired glucose tolerance and impaired fasting glycemia. To date, it is obvious that the development of prediabetes lead not only to the higher risk of diabetes mellitus in the future, but also of cardiovascular diseases. Factors that increase the risk of cardiovascular events in patients with prediabetes includeare the following: insulin resistance, accompanied by arterial hypertension and dyslipidemia, and postprandial hyperglycemia. Therefore, it is very important to timely identify patients from the risk group, diagnose and treat carbohydrate metabolism disorders already at the stage of prediabetes. Also it is very important to identify the patients from the risk group, diagnose and treat carbohydrate metabolism disorders at the stage of prediabetes. Treatment of patients with prediabetes implies, first of all, lifestyle modification (moderate hypocaloric nutrition with predominant restriction of fats and simple carbohydrates and regular physical activity of moderate intensity) in order to reduce weight. If lifestyle changes are ineffective, drug therapy may be prescribed. The article discusses the studies conducted to assess the effectiveness of lifestyle modification, as well as various options for antihyperglycemic therapy (metformin, glucagon-like peptide receptor agonists, alpha-glucosidase inhibitors, orlistat) for the treatment of patients with prediabetes. It also provides data on long-term follow-up of patients with prediabetes who received different treatment options.

At the moment, lactate-acidosis coma in patients with diabetes mellitus is considered a rare and extremely urgent condition that occurs in patients with concomitant diseases as well as when taking the most widely used sugar reducing drug – metformin. This article describes a case of lactate-acidosis coma with a fatal outcome, which occurred against the background of taking metformin and alcohol abuse, in a woman with type 2 dia-betes mellitus aged 48 years.

Background: The prevalence of obesity and metabolic abnormalities is increased patients with mental disorders receiving psychopharmacotherapy, which significantly impairs their treatment adherence.Aims: To evaluate the efficacy and safety of metformin in prevention and treatment obesity and overweight in patients with mental disorders receiving antipsychotics.Materials and methods: This was an open-label, prospective, randomized, placebo-controlled study of female patients with mental disorders (age, 18 to 50). The patients were randomized into two groups in a 2:1 ratio: the treatment group received metformin and the control group received placebo. Metformin was administered at a starting dose of 500 mg daily, with subsequent up-titration every 2 weeks when necessary, up to 2000 mg daily. The treatment duration was 6 months.Results: Baseline BMI in the treatment group (N=62) was 27,3 [24,0; 30,4] kg/m2; it decreased to 26,0 [22,5; 30,5] kg/m2, p < 0.0001, Wilсoxon test) after 6 months of treatment. The patients receiving metformin decreased their body weight by 3 [-6; 0] kg, or -4,0 [-8; 0] %. In the placebo group (N=30), the baseline BMI was 27,5 [24,0; 32,0] kg/m2 and increased to 28,2 [25,8; 34,0] kg/m2 at 6 month (p=0.001, Wilсoxon test), or 3 [1; 6] kg. After 6 months of treatment, the difference in BMI between the metformin and placebo groups was significant (26,0 и 28,2 kg/m2, respectively, р=0,027, Mann-Withney test). Six (6) of 62 patients treated with metformin had side effects and were switched to an equivalent dose of prolonged release metformin, with reduction of side effects in 5 of them.Conclusions: The use of metformin in patients with mental disorders receiving antipsychotics allows for reduction or stabilization of body weight in 80% of cases, with ≥5% decrease of body weight in 44% of patients. It is recommended to start metformin at a dose of 500 mg daily with subsequent up-titration of up to 2000 mg if necessary.

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease. It is characterized by persistent pruritus, usually occurring after 30 weeks of pregnancy, and by elevated levels of bile acids and transaminases, which decrease over the course of 2-3 weeks postpartum. [1,2]The occurrence of ICP in the mother may be associated with significant complications in the fetus, such as: preterm labor, intrauterine asphyxia, or sudden fetal death. Currently, the treatment of choice is ursodeoxycholic acid (UDCA).[2,6] Recently, it was observed that the administration of metformin in cases not responding to standard therapy improved lipid disorders in pregnant women. The aim of the study: The aim of the study is to present the possibility of using metformin in the treatment of ICP in pregnant women not responding to standard treatment and to present a clinical case.. Material and methods: The work is a review of the literature on the management of ICP and the use of metformin in the treatment of lipid metabolism disorders, as well as a brief case report of a patient with intrahepatic cholestasis of pregnancy. Description of the state of knowledge: Metformin is an oral antidiabetic drug belonging to the group of biguanides. However, the latest observations show that metformin also has a beneficial effect on the liver function and on the lipid metabolism in pregnant women. In these patients, the levels of bile acids and liver enzymes decreased after the use of metformin. Summary: The mechanism of action of metformin explaining its beneficial effect on the lipid metabolism in pregnant women with intrahepatic cholestasis is not fully understood.

Introduction and purpose Insulin resistance is a state of decreased tissue sensitivity to insulin, despite normal or elevated levels of this hormone in the blood serum. People with insulin resistance for a long time do not show symptoms, which makes it particularly difficult to detect and treat in early stages. It mainly leads to impaired glucose homeostasis and the development of type 2 diabetes, which contributes to the exacerbation of the global problem that diabetes has become. This results in the search for innovative therapies that will help combat insulin resistance better and better. The purpose of this study is to highlight the complexity of the IR and review the current literature for non-pharmacological and pharmacological possibilities of treatment for insulin resistance. Description of the state of knowledge Due to the increase in obesity and the metabolic syndrome, the number of people suffering from insulin resistance is constantly increasing. In modern times, there are various diagnostic and therapeutic methods that affect the course of insulin resistance. Early detection and introduction of appropriate therapy become the main goal in preventing complications that may occur in the course of this disease. Summary Treatment methods for insulin resistance can be divided into two groups - non-pharmacological and pharmacological. Both of them are often used together in the form of combination therapy aimed at obtaining the best results in the treatment of insulin resistance. For people for whom known therapies do not work, researches for new treatments is becoming a hope.

Polycystic ovary syndrome (PCOS) is a known disease among endocrinologists and gynecologists. The aforementioned disease entity affects up to six to twelve percent of women of reproductive age. [1] In 2017, the incidence among women of childbearing age was 82.44 per 100,000 population. A decade ago, it was 1.45% lower.[2] PCOS is a disease in which we have abnormal hormone levels. The result may be a problem with regular menstruation, problems with becoming pregnant, acne or excessive body weight. [3] Most often, patients arediagnosed only when complications occur. It is closely related to asignificant reduction in living standards. There are problems such as hair loss, acne and infertility.

Type 2 diabetes mellitus is a serious medical and social problem. The danger of the disease is associated with epidemic growth rates and chronic complications, leading to early disability, decreased quality of life and mortality. The prevention of diabetes complications is based on the optimal glucose-lowering therapy with the achievement of target metabolic parameters from the date the diagnosis of T2DM was established and throughout the patient’s life. The complex pathogenetic mechanisms of T2DM are the underlying rationale for drug therapy with a simultaneous effect on various disorders, which will provide a greater hypoglycemic potential and maintain effective glycemic control as T2DM progresses. The main reasons for poor disease control include clinical inertia, untimely intensification of drug therapy, and the use of treatment regimens that are insufficiently effective given the progressive course of the disease. The therapy for T2DM is based on clinical guidelines. The pathogenetic therapy options associated with the use of vildagliptin and metformin are considered. Much attention in modern diabetology is paid to the study of the influence of various therapeutic approaches on the disease progression rates from the perspective of improving prognosis and long-term maintenance of target glycemic control. The advantages of combined glucose-lowering therapy at the onset of T2DM are considered in comparison with the stepwise intensification of glucose-lowering therapy. The VERIFY study examined the long-term efficacy and safety of two treatment approaches: early vildagliptin and metformin combination therapy versus the traditional stepwise approach starting with metformin as initial therapy. The combined glucose-lowering therapy is an important direction in the treatment of patients with newly diagnosed type 2 diabetes.

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Treatment difficulties of COVID-19 have determined the need to identify predictive risk factors for the development of a complicated disease course, critical conditions and death. Endocrine and metabolic abnormalities associated with obesity, including impaired insulin sensitivity, chronic inflammation and impaired lipid and fatty acid metabolism, increase immunological dysregulation and make these patients more susceptible to developing infectious diseases. Research data allows us to single out obesity as a risk factor for the aggravated course of COVID-19, as well as a longer period before the virus elimination, and, therefore, the risk of virus transmission. Potentiation of cardiovascular risk factors, an increase in the production of pro-inflammatory cytokines, coagulopathy are factors in the development of unfavorable outcomes in such patients.This review presents literature data on the features of the course and the mechanisms of development of complications in patients with new coronavirus infection and obesity. Taking into account the need to restore metabolic health to increase the adaptive and resistant capacities of the body in the face of the threat of a new increase in the prevalence of COVID-19, the possibilities of treating obesity using a combined preparation containing sibutramine and metformin in one tablet, are discussed.

The aim of our research is investigating the changes in the level of interleukin 1β in experimental animals, which were simulated diabetic retinopathy and against the background of its correction. The obtained indicate that already on the 30th day of the development of experimental diabetic retinopathy, a significant increase in the pro-inflammatory cytokine level draws attention. Analyzing the data of group No. 3, it was established that the correction of the pathological condition with hypoglycemic agents has a positive effect but requires the involvement of additional means of correction in addition to the normalization of the level of glycemia. The results of the 4th experimental group indicate that the involvement of a nitric oxide donor and aflibercept in the correction of diabetic retinopathy has a positive effect on the reduction of the level of Interleukin 1β, but it does not reach an approximation to the norm. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group No. 5) gives positive results, but less pronounced than involvement in the complex correction of L-arginine solution in the study of nitric oxide synthases, in the analysis of the pro-inflammatory cytokine level the results are better. It is also worth noting that this method of correction is not characterized by longevity and on the 180th day there is already a pronounced decrease in its effectiveness. It was found that in rats in which diabetic retinopathy was modeled with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group No. 6), there is a pronounced effectiveness of the proposed method of correction in comparison with the previously considered methods. As for the correction applied in the 7th group, in the first and second stages, the inflammation indicator is more elevated compared to the two previous groups (No. 5 and No. 6), but in the third stage, a marked decrease in the level of the marker was established, which indicates the effectiveness of the correction of the 7th group at more distant stages of the experiment.

Diabetes mellitus (DM) is a recent problem due to the high prevalence of the disease and the high mortality of patients. The most common complications of type I and II diabetes include heart and kidney damage. Metformin, as a first-line drug in the treatment of type 2 diabetes, are known to reduce the risk of cardiovascular and renal complications. Recently, metformin has been shown to increase H2 S in the organs of rats, which is a known cardio- and nephroprotector. However, the effect of metformin on H2 S metabolism in the heart and kidneys in experimental diabetes remains uncertain. The ability of H2 S donors to modify the antidiabetic effect of metformin is also unknown. Objective: to evaluate the effect of metformin and its combination with sodium hydrogen sulfide on H2 S system, the content of profibrogenic mediator galectin-3, the activity of free radical oxidation of lipids and proteins in the heart and kidneys of rats with streptozotocin-induced diabetes. Object and methods of research. The experiments were carried out on 40 white laboratory rats of both sexes, weight 220-280 g. DM model was initiated by a single intraperitoneal injection of streptozotocin (40 mg/kg) in three groups of animals. From the 3rd to the 28th day after streptozotocin injection, one group of animals was administered metformin (500 mg/kg) intragastrically once per day, and the other group along with metformin was administered a H2 S donor – NaHS • H2 O (3 mg/kg) once per day intraperitoneally. Peripheral blood glucose was measured using a glucometer, galectin-3 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit in myocardial and renal homogenates, H2 S content, cystathionine-γ-lyase (CGL) activity, levels of malonic dialdehyde (MDA group) and carbonic acid. Statistical processing of the results was performed using SPSS Statistica 17.0. Research results. According to our results, a single injection of streptozotocin caused a number of metabolic disturbances : an increase in blood glucose by 4.6 times (p

Almost half of deaths in Poland (approximately 49%) are caused by cardiovascular system diseases. It means that in 2018 it contributed to the death of over two hundred thousand people in our country. Myocardial infarction, stroke and heart failure are the most common of cardiovascular diseases (CVD). The main risk factor for progression of cardiovascular diseases is type 2 diabetes mellitus (T2D). It is estimated that almost 3 million people suffer from T2D in Poland. Metformin is a promising medicine that reduces cardiovascular risk in patients with T2D. It is currently used as the first line drug in patients suffering from T2D. The aim of the presented article is to review current research on the effectiveness of the metformin as a medicine that reduces cardiovascular risk in patients with T2D. Metformin is the oldest and most commonly used medicine that reduces the concentration of glucose in the peripheral blood in patients with T2D. Due to its very good safety profile, low cost and high effectiveness, metformin is used in the first-line treatment for T2D. Recent studies indicate its protective effect by vasodilation, reducing the size of myocardial infarction, inhibiting apoptosis of cardiomyocytes or reducing oxidative stress. Currently, metformin can be seen to have a great potential in the treatment of cardiovascular complications occurring in the course of T2D. Despite the fact that this medicine has been on the market for many years, the studies on its cardioprotective effects have been carried out for a relatively short period of time. It is possible that the detailed understanding of all mechanisms of action of metformin will lead to future advances in the treatment of not only T2D, but also cardiovascular and cancer diseases.

Type 2 diabetes mellitus (DM) is one of the most common diseases in the world. According to data of the International Diabetes Federation, there are more than 425 million people suffering from this disease in the world. The course of type II DM is accompanied by a progressive lesion of the macrovasculature, which is associated with an increase in the risk of developing atherosclerosis in this category of patients by 4-5 times in comparison with patients without diabetes. This in turn leads to some complications such as blindness, strokes, vascular damage of the limbs and chronic renal failure (CRF), which is often the leading cause of death. The occurrence of any inflammatory process against the background of diabetes is a significantly aggravating factor for the patient, as the body’s reserves are reduced, especially in the presence of CRF. The need for urgent surgical intervention in a patient with an inflammatory process against the background of diabetes is another stress factor. In addition, patients with DM are constantly taking hypoglycemic drugs, the effect of which in a stressful situation is not always predictable for the patient and therefore these drugs should be canceled. However, if the patient has CRF and long-term administration of drugs, their effect does not immediately stop. The combination of all the above points puts the patient with DM at a high risk group for the development of serious complications requiring intensive care (IT). Such complications in the early postoperative period may be lactic acidosis, persistent hypoglycemia, electrolyte disorders, cerebral edema. In the clinical case the pathogenesis of the development of these conditions and IT methods are described. Conclusions have been drawn regarding the need for close attention of anesthetists and intensive care physicians during perioperative therapy in patients with DM, complicated CRF, and which are receiving metformin.

The high prevalence of metabolic syndrome (MS) and subclinical hypothyroidism (SHypo) creates danger of integral cardio-metabolic risk (CMR). A concept is being developed to increase thyroid-stimulating hormone (TSH) levels as a component of MS with the key role of insulin resistance (IR). To identify groups of active intervention, the definitions of SHypo with age and gender characteristics are analyzed. The results of randomized clinical trials showed a higher incidence of prediabetes and type 2 diabetes mellitus (T2DM) in SHypo, as well as positive associations of autoimmune thyroiditis (AIT) with components of MS, especially in postmenopausal women. The association of SHypo with a systemic inflammatory response is analyzed, which can determine an increase in cardio-metabolic risk. At the same time, most of the thyroid dysfunction and the components of MS are associated with insulin resistance. The feasibility of SHypo treating with levothyroxine is discussed: the threshold parameters of thyroid-stimulating hormone (TSH) are not determined for initiating treatment; in old age, due to a decrease in the need for thyroid hormones, an increase in the upper reference range of TSH is discussed; there is no evidence of a decrease in cardiovascular risk and mortality. In parallel, data have been accumulated on a decrease in TSH levels in overt and subclinical hypothyroidism in patients with MS and T2DM with metformin therapy. The gender effect of metformin on the activity of the hypothalamus-pituitary-thyroid axis was suggested, its new antihyperglycemic mechanism of action, including the activation of the AMP protein kinase (adenosine monophosphate (AMP) -activated protein kinase) in the pituitary gland, was revealed. It is possible that metformin is a promising therapeutic agent not only for patients with type 2 diabetes and thyroid disease, but also for MS and obesity. The multifaceted capabilities of metformin, including the correction of peripheral and central insulin resistance and a decrease in TSH levels in patients with SHypo, emphasizes an integrated approach to the prevention of CMR. The prolonged release form of metformin has several advantages: better tolerance, greater efficiency in the correction of IR, lipid and carbohydrate metabolism, additional indication - treatment of prediabetes, the possibility of prescribing for creatinine clearance up to 30 ml/min.

The continuing growth in the prevalence of obesity in close connection with the tandem of a number of chronic diseases, each of which is in the nature of a non-infectious epidemic, indicates an obesity syndrome. This is one of the most complex and expensive diseases, taking into account its cardio-metabolic and oncological risk, chronic progressive course and recurrent nature. Such a situation dictates the necessity to clarify the pathogenetic approaches to the problem, based on the principles of early treatment, before the debut of comorbid nosology’s. With the multifactorial nature of obesity, it is difficult to single out the principal directions of intervention with the goal of not only reducing body weight, but especially its stabilization. The accumulated data on new pathogenesis links are analyzed: dysfunctions of the microbiota and entero-endocrine system of the gastrointestinal tract with impaired incretin synthesis, metainflammation, peripheral and central insulin resistance, which integrally changes intracellular energy metabolism through a change in the activity of the AMP-activated protein kinase and is associated with systemic inflammatory response. These links are interconnected by the axis: “intestine – brain – liver”, which explains the relationship of obesity with multiple multidisciplinary pathology and reflects the necessity for multidirectional effects. From the point of view of the definition of obesity as a brain disease, with an emphasis on the hypothalamus, the feasibility of an approach to weight loss only through lifestyle changes and the problem of the slipping effect is discussed. The necessity for weight loss is discussed along with the regulation of metabolic imbalance. The feasibility of combined pharmacological intervention is substantiated. ReduxinForte is considered as the drug of choice with a detailed analysis of its components, metformin and sibutramine, their ability to correct various parts of the pathogenesis of obesity and pleiotropic effects to achieve stable metabolic control and reduce the risks of complications.

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications. However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target. A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients.

The aim of the study was to analyze changes in erythrocyte diphosphoglycerate levels and Willebrand factor in the development of hypoxia and endothelial dysfunction in experimental diabetic retinopathy. The study was performed on white Wistar rats weighing 180-200 g. Our results indicate the development of hypoxia on the 30th day of development of experimental diabetic retinopathy with subsequent progression of pathological changes on the 60th and 180th day of the study, as evidenced by the decrease level of 2,3 diphosphoglycerate of erythrocytes in the 2nd group (p rd stage of the experiment (p rd stage of the experiment (p

To date, the key role of endothelial dysfunction in the occurrence and progression of diabetes mellitus and diabetic retinopathy has been proven. The study was performed on white Wistar rats weighing 180-200 g. According to the tasks, the animals were divided into 7 groups. Our results indicate a violation of vasodilation on the 30th day of experimental diabetic retinopathy with subsequent progression of pathological changes on the 60th and 180th day of the study, as evidenced by a decrease in the content of S-nitrosothiols in group 2 (p rd stage. When analyzing the data of group № 3, it was found that the correction of the pathological condition with the help of hypoglycemic agents has some positive effect, but does not allow to significantly adjust the pathological development of reduced vasodilatory potential. The results of the 4th group indicate that the involvement of nitric oxide donor and aflibercept in the correction of diabetic retinopathy corrects the pathological changes and helps to restore the physiological pathway of nitric oxide synthesis and vascular tone, the maximum effect is observed on the 180th day of the experiment, but normative cannot be achieved. It is observed that the correction of the simulated pathological condition by reducing hyperglycemia, administration of aflibercept and bromfenac (group № 5) gives positive results in the first stage, but less pronounced than involvement in the complex correction of L-arginine solution in subsequent stages. It was found that rats in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac (group № 6) have a pronounced tendency to normalize the studied marker of hypoxia in comparison with the previous methods in the second stage. nitrosothiols at the time of reaching the 3rd stage is reduced. The obtained data suggest that the method of correction chosen in group 7 (correction of hyperglycemia, aflibercept, L-arginine and citicoline solution) more pronouncedly normalizes the content of the vasodilation marker compared to other groups of our experiment, which is pronounced in long-term correction - on 180th day.

A rare case of the multiple myeloma is written. The patient developed the extramedullary lesions with a primary lesion of the duodenum as a massive plasmacytoma with the bleeding, as well as damage to the pancreas and lymph nodes. The patient received several lines of therapy, including proteasome inhibitors and antitumor immunomodulators before the onset of extramedullary lesions. Extramedullary relapse was detected by positron emission tomography combined with CT (PET/CT) before the appearance of obvious clinical signs, which emphasizes the advisability of including PET/CT in the diagnostic algorithm for such patients. Repeated therapy with the previously used bortezomib or lenalidomide was ineffective, there was a further increase in plasmacytoma in duodenum and its bleeding, which led to severe anemia. The combination of carfilzomib with pomalidomide and dexamethasone allowed to achieve complete remission after three cycles of treatment. In this clinical case, we additionally used clarithromycin and metformin to improve the anti-myeloma activity of combination of main treatment. In a brief review of the literature, the frequency of extramedullary lesions, the causes of the appearance of extramedullary lesions, and approaches to diagnosis and therapy are analyzed. Extramedullary lesions with multiple myeloma are a dangerous manifestation of the clonal evolution of the disease, in which the treatment options are still limited, therefore, the demonstration of successful treatment with carfilzomib shows the value of new methods of treatment, as well as the potential effects on the tumor cell when redesigning drug prescriptions.

BACKGROUND: Metabolic syndrome and obesity are often precursors of type 2 diabetes mellitus (DM), and current recommendations indicate the advisability of early initiation of drug therapy at the stage of prediabetes. Drugs with incretin activity are one of the priority groups for monotherapy of type 2 diabetes in the onset of the disease, and certain drugs are used to treat obesity. GPR119 agonists increase the secretion of endogenous incretins, and their effectiveness in the treatment of type 2 diabetes and obesity in mono- and combination therapy is currently being actively studied. AIM. To evaluate of the effect of administration of a GPR119 receptor agonist, its combination with metformin or sitagliptin on body weight, food intake and glycemia in rats under a high-calorie diet. MATERIALS AND METHODS: The study was conducted on 56 outbred female rats aged 7–8 months and an initial weight of 305–320 g. Compound ZB-16 is a highly active GPR119 receptor agonist (EC50 = 7 nM). For 12 weeks, the animals were kept on a high-fat and carbohydrate diet and at the same time received the compound ZB-16, metformin and sitagliptin, or its combination (ZB-16 + metformin and ZB-16 + sitagliptin). During the experiment, the weight of the animals, the mass of feed eaten, as well as the level of glycemia after 6 hours of fasting and with an oral glucose load were assessed. RESULTS: In animals of the control group that were on a high-calorie and fatty diet for 12 weeks, an increase in body weight, glycemia and a decrease in the rate of glucose utilization were observed. The introduction of the GPR119 agonist (ZB-16) for 12 weeks led to a significant reduction in the amount of food consumed, limited weight gain and prevented the development of carbohydrate metabolism disorders. The addition of sitagliptin and especially metformin to therapy with the GPR119 agonist significantly increased the effectiveness of therapy compared to the control group, which was expressed in the normalization of animal body weight and glycemia (p

Recent studies have shown that immune system cells take an active part in the regulation of metabolic homeostasis. Disruption of the interaction between the immune system and metabolic processes makes a major contribution to the current epidemic of a number of non-communicable metabolic diseases. Due to central and peripheral insulin resistance, obesity is closely associated with type 2 diabetes mellitus. Many mechanisms are involved in the genesis of insulin resistance including chronic inflammation in metabolically active tissues (adipose tissue, intestines, muscles, pancreas, liver), as well as in the central nervous system. Potential triggers of obesity-induced metainflammation are cellular hypoxia, mechanical stress of the fat cells, excess of free fatty acids and lypopolysaccharides. Weight loss is a key factor to eliminating inflammation and improving tissue insulin sensitivity. This review presents literature data on the mechanisms of metainflammation in obesity. Taking into account the contribution of metainflammation to the pathogenesis of the disease, the possibilities and prospects of obesity therapy are discussed.

Hyperglycemia stimulates the development of oxidative stress, which in turn is a powerful pathophysiological mechanism for the development of microvascular complications in diabetes. Increased production of reactive oxygen species is observed both during development and during the progression of diabetic retinopathy.The study was performed on white Wistar rats weighing 180-200 g. According to the tasks, the animals were divided into 7 groups: 1st group - 60 intact animals; Group 2 - 60 animals in which diabetic retinopathy was simulated without further correction. Group 3 - 60 animals, which simulated diabetic retinopathy with subsequent correction of hyperglycemia; Group 4 - 60 animals in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept and L-arginine solution; Group 5 - 60 animals in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept and bromfenac; Group 6 - 60 animals in which diabetic retinopathy was simulated with subsequent correction of hyperglycemia, administration of aflibercept, L-carnitine and bromfenac; Group 7 - 60 animals, which simulated diabetic retinopathy with subsequent correction of hyperglycemia, the introduction of aflibercept, a solution of L-arginine and citicoline.The results indicate the development of oxidative stress from the 30th and with subsequent progression on the 60th and 180th days of experimental diabetic retinopathy, which is confirmed by a decrease in peroxidase activity in the 2nd group, the maximum of which is observed in the 3rd stage. Correction with hypoglycemic agents in group 3 had a positive effect, but was not able to restore the activity of the antioxidant enzyme, so there was a need for additional drugs. The use of aflibercept and nitric oxide donor in group 4 to correct the development of diabetic retinopathy had a positive effect on increasing the activity of peroxidase, which peaked on the 180th day of the experiment, but did not reach the control values. The combined administration of bromfenac and aflibercept in group 5 was shown to significantly increase antioxidant activity, but not as significantly as in group 4. Administration of aflibercept, L-carnitine, and bromfenac to group 6 animals was shown to restore antioxidant protection as early as day 30 and was continued on days 60 and 180 of the study, but the results did not reach control values. The combination of metformin, aflibercept, L-arginine and citicoline in rats of the 7th group proved to be the most effective correction, as evidenced by the normalization of peroxidase activity on the 30th and 60th day of the experiment, and on the 180th recovery of marker activity to control values was recorded.

The aim of our study was to analyze the changes in the blood glucose level in experimental animals that simulated diabetic retinopathy and against the background of its correction. The obtained results show the development of experimental diabetes when streptozotocin is administered at a dose of 55 mg/kg of animal weight against the background of a high-fat diet. Correction with hypoglycemic agents in the 3rd group had a positive effect, but it was not able to completely normalize the level of glycemia, so the need arose for the use of additional agents. The use of aflibercept and a nitric oxide donor in the 4th group had a more pronounced positive effect compared to the 3rd group, but the result did not reach the control indicators. Combined administration of bromfenac and aflibercept in the 5th group showed itself to be less effective in the study of the blood glucose level at all stages in comparison with the data of the 4th group, in which the NO donor was involved in the correction. Administation of aflibercept, L-carnitine and bromfenac to the animals of the 6th group had a more pronounced positive effect in comparison with the group No. 5, but did not reach the values of the 4th group of the experiment. The most effective correction was the combination of metformin, aflibercept, L-arginine and citicoline in rats of the 7th group, which is evidenced by the normalization of the level of the studied indicators on the 30th and 60th days of the experiment, and on the 180th, the most pronounced decrease was recorded hyperglycemia.

Metformin is one of the oldest and at the same time relevant and effective drugs for the treatment of type 2 diabetes. At the same time, the mechanism of the hypoglycemic effect was not completely clear until recently. Current data suggest that the mechanism of action of metformin contributes to the development of an anti-inflammatory effect, as well as a decrease in the level of uric acid, and its use can be potentially useful in patients with hyperuricemia and gout.