В течение последних 15 лет в терапии сахарного диабета 2 типа (СД2) все шире используются агонисты рецепторов глюкагоноподобного пептида-1 (арГПП-1), ингибиторы дипептилпептидазы 4-го типа и инги- биторы натрий-глюкозного котранспортера 2-го типа (иНГЛТ-2). арГПП-1 и иНГЛТ-2 кроме сахароснижаю- щего действия демонстрируют кардио-нефропротективные эффекты. Вызывает интерес использование препаратов данных классов в реальной клинической практике в Москве в современных условиях. ЦЕЛЬ: изучить практику использования современных классов сахароснижающих препаратов у больных СД2 в Москве. МАТЕРИАЛЫ И МЕТОДЫ: с помощью выборок из Московского сегмента Федерального регистра са- харного диабета (ФРСД) был проведен анализ использования современных классов сахароснижающих препаратов у больных СД2, в частности препаратов с кардио-нефропротективными свойствами в когортах пациентов очень высокого сердечно-сосудистого риска. РЕЗУЛЬТАТЫ: На 01.01.2023 г. 136.869 чел. (41,4% от всех больных СД2) получали препараты новых классов [иНГЛТ-2 (70.773 чел. – 21,5%), иДПП-4 (57.153 чел. – 17,3%), арГПП-1 (8.943 чел. – 2,7%)]. Доля пациентов с ХСН, получающих иНГЛТ-2, за период наблюдения с 01.01.2021 по 01.01.2023 г. выросла в 3 раза (с 16,7% до 52,1%), абсолютное число - в 12 раз (с 1.209 до 14.527 чел.). Доля пациентов, перенесших ИМ, получающих иНГЛТ-2 и/или арГПП -1 выросла в 4 раза (с 10,4 до 42,3%), абсолютное число таких пациентов - 1.844 до 8.257 чел. Доля пациентов, перенесших ОНМК и получающих иНГЛТ-2 и/или арГПП -1 также выросла в 4 раза (с 6,2 до 25,7%), абсолютное число - с 1.095 до 4.448 чел. ВЫВОДЫ: проведенный анализ демонстрирует рост числа больных СД2, получающих иДПП-4, иНГЛТ-2 и арГПП-1 по данным Московского сегмента ФРСД.

Coding of the causes of death of patients with diabetes mellitus (DM) in the Russian Federation is one of the long-discussed problems, due to the comorbidity of diabetes and cardiovascular diseases (CVD) and a number of contradictions in the key regulatory documents regulating the statistics of mortality in this category of patients, which acquires particular relevance in the context of the coronavirus pandemic, due to its negative impact on the outcomes of the course of COVID-19 and mortality risks. In pursuance of the decisions of the Minutes of the meeting of the working group under the project committee of the National Project «Health» on identifying patterns in the formation of mortality rates of the population dated January 20, 2021 No. 1, chaired by Deputy Prime Minister of the Russian Federation T.A. Golikova, experts of two directions - endocrinology and pathological anatomy, prepared a Draft of agreed recommendations on the Rules for coding the causes of death of patients with diabetes, causing the greatest problems in terms of the use of ICD-10 when choosing the initial cause of death, including in the case of death from CVD and COVID-19.

the routine management of patients with pulmonary arterial hypertension (PAH). Like patients with other chronic cardiovascular diseases, PAH patients are not at higher risk of a new coronavirus infection. However, in the current epidemiological situation, the problems of managing high-risk groups are sharply indicated, in which the severe course of COVID-19 with a higher lethality is more often noted. Undoubtedly, рatients with different forms of pulmonary hypertension belong to the high-risk group, considering both the presence of severe life-threatening cardiovascular pathology and background pathology in cases of the associated forms of the disease. At the same time, the first foreign experience indicates a rather low incidence and relatively favorable course of COVID-19 in PAH, which allows to formulate a number of hypotheses that will be confirmed or rejected in the near future. The unique problems of managing patients with PAH are those associated with changes in generally accepted standards of medical care and patient routing, which is especially important for patients receiving PAH-specific drugs. The problems of a complex assessment of the risk of possible infection in the event of hospitalization or an outpatient visit of patients on the one hand, and on the other, the risk of PAH progression with a delay in starting treatment, are a dilemma that requires an individual solution. Based on an analysis of current data, this review summarizes the main approaches to managing patients with PAH in the current epidemiological situation.

BACKGRAUND: The need to create a national questionnaire for screening the population for disorders of carbohydrate metabolism. AIMS: Develop a highly specific and sensitive questionnaire-calculator of the risk of prediabetes (PreD) and diabetes mellitus type 2 (DM2T) based on depersonalized data of individuals who have these diagnoses confirmed in the national epidemiological study NATION . METHODS: The express method of prediabetes (PreD) and diabetes mellitus type 2 (DM2T) risks has been created, validated and proposed for clinical usage for the first time in the Russian Federation, it was based of NATION epidemiologic study database (more than 26 000 participants). The following mathematical instruments have been used: mathematic modelling, main components methodology, binary variables, correlation analysis and single-factor analysis of variance . RESULTS: Highest coefficients of logistic regression for PreD (p<0.05) were identified for age — ≥52 years old for women and ≥59 years old for men (1,48); body mass index ≥31 (0.75); waist circumference ≥100 сm for women and ≥112 cm for men (0.90). In the same time coefficients for DM2T were for for age — ≥52 years old for women and ≥59 years old for men (1,24); body mass index ≥31 (1,19), high blood fasting glucose analysis in the past (1,37); waist circumference / hip circumference ratio ≥0.85 for women and ≥0.92 for men (1,05), high blood pressure (0.69). Correlation coefficients were taken into account and score has been used for specialized questionnaire creation. Sensitivity and specificity for PreD were 83,8% and 59,3% accordingly, for DM2T — 85,4% and 73,6% accordingly. DM2T may be suspected when total score of questionnaire is 11 and higher, and PreD — when total score will be ≥7 and <11. CONCLUSIONS: The calculator based on questionnaire (DIARISK) allows to separate of potential patient for PreD and DM2T confirmation during first examination or dispanserization. A patent for innovation has been issued.

BACKGROUND: The number of patients with chronic metabolic disorders such as obesity, type 2 diabetes mellitus (T2D) and non-alcoholic fatty liver disease (NAFLD) is growing at an alarming rate worldwide in both developed and developing countries. In the world, the prevalence of NAFLD is approaching 25%. Among patients with T2D, 70–80% are diagnosed with NAFLD. Insulin resistance (IR) is recognized as one of the main pathogenetic factors in the development of the most common chronic liver disease — NAFLD. AIM: Our search work was aimed at determining the contribution of the degree of IR to the progression of NAFLD; compare the gold standard for the determination of IR (clamp) and the mathematical model (HOMA-IR). METHODS: An observational one-stage open comparative study was conducted on the basis of the case-control principle. The objects of the study were overweight and obese patients who had not previously been diagnosed carbohydrate metabolism disorders, without secondary causes of fat accumulation in the liver. During the examination, clinical and laboratory studies were carried out, IR indices (M-index, HOMA-IR index) were obtained, a diagnosis of carbohydrate metabolism disturbance (or its absence) was made, a liver biopsy was made, morphological and clinical diagnoses were made. RESULTS: The analysis included information about 60 patients, they are divided into 3 groups: without NAFLD (7 people), with steatosis (18 people), with non-alcoholic steatohepatitis (NASH) (35 people), groups are comparable by age, gender, and body mass index (BMI), glycated hemoglobin. When assessing the degree of IR using the hyperinsulinemic euglycemic clamp test, 19 showed a severe degree of IR, 28 had a moderate degree, 8 had a mild degree, and 5 had no IR. In the three studied groups, the median IR corresponded to an average degree and did not significantly differ. When comparing the gold standard for determining IR and the mathematical model (HOMA-IR) in the studied groups, an negative significant correlation was revealed (p = 0,0001). CONCLUSIONS: In the course of our study, no correlation was found between the degree of IR and the severity of NAFLD. This result allows us to think about other pathogenetic factors that affect the progression of NAFLD.

Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research. Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016. Materials and methods : The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters. Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUC ins0-T , and 85.43% - 115.64% for the PD-parameter AUC GIR0_T , which fall within the specified limits of 80% - 125% to establish comparability between drugs. Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®.

BACKGROUND: Diagnostic of diabetes mellitus type 2 (DM2T) in time is very actual for treatment and prevention of potential complications of illness. Fasting blood glucose test (FBG) is a widely used method of primary DM2T diagnose. Glycated hemoglobin (HbA 1c ) test is an alternative and used more rarely due to expensive. AIM: Modelling of comparative expenditures for DM2T control in cases of primary diagnostic by HbA 1c test or FBG test usage in 20-years horizon. METHODS: Retrospective analysis of aggregated epidemiological Russian NATION study data in 810 patients with prediabetes and DM2T with both analysis performed, with sensitivity and specificity of each is detected. The simulation model of DM2T outcomes has been used for Health Technology assessment (direct and indirect costs of Diabetes control during 20 years). Three algorithms of the DM2T treatment were investigated for understanding of expenditures in case on diagnostic on-time and case of late verification with metformin, gliflozines, gliptins, Glucagon-like peptide-1 receptor agonists, basal insulin analogs and their combinations. RESULTS: FBG test has more negative results for DM2T diagnostics in compare with HbA 1c analysis (77,4% and 36,5% accordingly). Amount of false negative results in FBG test in 3 times more often occurred in comparison with HbA 1c . HbA 1c test in 3 times more precisely than FBG test for carbon metabolism abnormalities detection. Diagnostic in time with HbA 1c test in compare with late process of illness detection by FBG can cut common expenditures on 26,3-27,7% depending on treatment option due to macrovasular complications decreasing. Disability rate is expected decrease on 21% to 20-th year in case of diagnostic with HbA 1c performing instead FBG test. CONCLUSION: HbA 1c test has diagnostic advantages in compare with FBG test for primary investigation (dispanserization). Direct and indirect expenditures in average for one patient with DM2T on 20-years horizon including cost of drugs, analysis, complications, disabilities are less in case of diagnostic in time with HbA 1c test in comparison with late diagnostics in case of FBG test execution.

Цель исследования. Сравнить овариальный резерв у здоровых женщин репродуктивного возраста - носительниц антитиреоидных антител (АТА) - и у здоровых женщин репродуктивного возраста, негативных по АТА. Материалы и методы. Обследовано 70 здоровых женщин молодого репродуктивного возраста (от 18 до 38 лет) в состоянии эутиреоза. Участницы разделены на равные группы (n=35) в зависимости от статуса по наличию АТА (к тиреопероксидазе, тиреоглобулину). На 2-4-й день менструального цикла определяли следующие маркеры овариального резерва: сывороточные уровни антимюллерова гормона (АМГ), фолликулостимулирующего и лютеинизирующего гормонов, эстрадиола, тестостерона, а также ультразвуковые параметры - количество антральных фолликулов и объем яичников. Кроме того, для выяснения предрасположенности к преждевременной недостаточности яичников проводили анализ на количество CGG-повторов в гене FMR1. Результаты и обсуждение. Статистически достоверно различались такие параметры, как уровень эстрадиола и тестостерона, при этом различия не были клинически значимыми. Все оцениваемые параметры оказались в пределах нормы, основные показатели овариального резерва (уровень АМГ, количество антральных фолликулов) оставались в нормальном диапазоне. Увеличения количества повторов CGG в гене FMR1 не выявлено ни у одной из участниц исследования. Заключение. У здоровых женщины молодого репродуктивного возраста статус по АТА не оказывает непосредственного влияния на овариальный резерв.

В последние годы идет активное обсуждение связи сахарного диабета (СД) и хронических заболеваний печени (ХЗП). С одной стороны, у пациентов с СД отмечается повышенный риск развития ХЗП, с другой - у пациентов с ХЗП очень часто выявляются нарушения метаболизма глюкозы, что в конечном счете приводит к нарушению толерантности к глюкозе и развитию СД. В настоящем обзоре освещены возможные причинно - следственные связи между некоторыми ХЗП и СД. Представлены механизмы, провоцирующие метаболические и аутоиммунные нарушения при развитии различных нозологий из группы ХЗП, приводящие к стеатозу, инсулинорезистентности, нарушению толерантности к глюкозе и развитию СД. Описаны определенные особенности оценки компенсации углеводного обмена у пациентов с нарушением печеночной функции, анемией и нарушениями белкового обмена.

Настоящая работа представляет собой обзор исследований, посвященных взаимосвязи применения новых технологий в лечении сахарного диабета (СД), а именно постоянной подкожной инфузии инсулина (ППИИ) и непрерывного мониторирования гликемии (НМГ), с психологическими характеристиками пациента. В статье обобщены как российские работы, так и исследования, выполненные за рубежом. В результате анализа было отмечено, что чаще рассматриваются психологические аспекты применения ППИИ и реже –НМГ. Большинство российских авторов сходятся в том, что использование технических средств ассоциировано с повышением психологического благополучия пациентов. Зарубежные исследователи в основном придерживаются той же точки зрения, но сообщают также и о менее однозначных взаимосвязях. Одним из наиболее значимых выводов, который можно сделать в результате проведенного анализа, является тот, что использование технических средств само по себе не гарантирует улучшения качества жизни (КЖ) и психологического благополучия. Такие технологии, как ППИИ и НМГ, несут в себе возможность для пациентов добиться повышения эффективности лечения СД, нормализации клинических и метаболических параметров и тем самым – изменения КЖ в лучшую сторону. Однако применение подобных устройств, как и многих других технических инструментов, сопряжено и с определенными психологическими трудностями как с точки зрения их освоения, так и влияния на субъективное благополучие пациентов. Своевременные диагностика и предупреждение подобных проблем должны стать одной из задач при подготовке пациентов к использованию рассматриваемых технологий. Только в сочетании с полноценным обучением (оптимально – по специализированным программам) и полноценной медицинской поддержкой они могут благоприятно воздействовать как на клинико-метаболические показатели, так и на психическую сферу и социальную жизнь пациентов.

Justification. The prevalence of type 2 diabetes is extremely high, and the number of such patients is constantly increasing. In 30-40% of patients, only insulin therapy can achieve compensation for the disease. Therapy with ready-made mixtures is considered as an alternative option in the initiation and intensification of insulin therapy. Rinsulin® mix 30/70 is a domestic biosimilar (bioanalogue) of Humulin® M3, a combination of a 30% solution of human insulin and a 70% suspension of insulin-isofan. The clinical research program for biosimilars of insulin preparations includes pharmacology studies: pharmacokinetics, pharmacodynamics and clinical safety research. Purpose. Evaluation of the biosimilarity of Rinsulin® mix 30/70 (bioanalog) and Humulin® M3 (original) preparations in the conditions of hyperinsulinemic euglycemic clamp in healthy volunteers. Materials and methods. The study was conducted on healthy male volunteers aged 18 to 50 years. Study design is a double-blind, randomized, crossover study of the comparative pharmacokinetics of drugs. The drugs were injected subcutaneously into the anterior abdominal wall at a dose of 0.4 IU / kg once. The duration of blood sampling to determine the pharmacokinetic parameters was 24 hours: the concentration of insulin in the blood was determined by enzyme-linked immunosorbent assay. Based on the level of glycemia, the glucose infusion rate was adjusted, the data of which were used to calculate the pharmacodynamic parameters. Results and discussion. Comparability of the main pharmacokinetic and pharmacodynamic characteristics of the Rinsulin® mix 30/70 and Humulin® M3 preparations in the conditions of hyperinsulinemic euglycemic clamp in healthy volunteers was noted. The confidence interval for the logarithmically transformed ratio of the values of the parameter C ins.max was 87.31-105.26%, and AuC ins.0-12 - 85.23-110.90%, which falls within the limits set by regulatory documents 80-125% to establish comparability between drugs. This confirms the high similarity of the reproduced Rinsulin® Mix 30/70 to the original drug. Of particular clinical significance is the synchronous onset of drug action, the time of onset of the maximum effect and duration of action. Adverse events in the study associated with the introduction of drugs were not recorded. Conclusions. Rinsulin® mix 30/70 and Humulin® M3 are equivalent.

Background : Despite the improvement in the quality of diabetes care in the Russian Federation (RF), coma remain one of the causes of death in patients with diabetes. Aim : To assess dynamic of epidemiological characteristic of acute complications in adult patients with T1D and T2D in 2013–16. Materials and methods : The database of the Russian Federal Diabetes register (81 regions). The indicators of coma for 2013–16 were estimated for 10000 adult patients with diabetes (>18 years). Results : In 2016, the prevalence of coma in RF was 225.9 with T1D and 11.6/10000 adults with T2D. For the period from 2007 the prevalence of ketoacidotic coma decrease three times in T1D, 4 times for T2D.Totally in 2016, 165 new cases of coma for both types of diabetes were registered, an average of 0.4/10000 adults. Interregional differences in the prevalence of coma were observed 0–4.2/10000 adults. The frequency of new cases of coma has a tendency to decrease: 0,9→0,4/10000 adults: T1D 5.7→3.4, T2D 0.6→0.2/10000 adults. When evaluating the structure of coma, redistribution is evident in their form. So in 2016 the proportion of hypoglycemic coma increased to 40.7%, and ketoacidotic coma decreased to 56.6% in T1D. With T2D, the difference expressed in a lesser degree. The mean duration of diabetes at the time of coma development increased with T1D from 3.8→9.1 years, with T2D 3.5→7.0 years. The maximum frequency of development of coma is recorded with the diabetes duration more than 30 years, regardless of the type. The patients’ age at the time of coma development in T1D increased to 27.5 years old, and in T2D it was 60.4 years, it didn’t change significantly. The assessment of glycemic control showed a significant improvement: a decrease in the proportion of patients with HbA1c≥ 9.0% (23% with T1D, 8.8% with T2D), an increase with HbA1c <7% (32.4% and 51.7%, respectively). The average value of HbA1c in 2016 with T1D – 8.21%, with T2D – 7.48%. Conclusions : It is established that the dynamics of the frequency of development of coma in 2013–16 in adult patients with diabetes in the RF has a stable tendency to decrease: 1.5 times with T1D and more than 3 times with T2D. It can be assumed that this is due to the improvement in the quality of diabetes care and glycemic control in general, as well as the use of modern medicines. Attention is required to draw to the high frequency of coma in T1D, the development of coma with a longer duration of diabetes, an increase in the proportion of patients with hypoglycemic coma. Significant interregional differences in the frequency of coma registration require additional analysis.

The Scientific Advisory Board, chaired by Professor G. R. Galstyan (cochair - A.V. Zilov), met in Moscow on 19 June 2018 to discuss the possibilities of improving the results of diabetes mellitus (DM) treatment by considering glycaemic variability (GV) as an additional criterion for effective glycaemic control (especially in patients receiving insulin therapy) and as one of the goals of treatment in patients with unstable glycaemia. The purpose of the working meeting was to develop a strategy for the introduction of GV as a predictor and as an additional criterion for assessing the effectiveness and safety of hypoglycaemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality. The aims of the working meeting were to conduct a comprehensive data analysis of the relationship between GV and hypoglycaemia; to gather and analyse published data and the experience of decrease in GV and improved outcomes of diabetes against the background of different types of insulin therapy; to compare existing methods of glycaemia monitoring and GV assessment and examine their validity and availability in real practice in the context of limited budget and to analyse the informativeness and clinical and prognostic significance of various parameters of GV assessment and to determine their reasonable ‘minimum’ for a comprehensive assessment of GV as a criterion for evaluating the effectiveness of DM treatment and the predictors of negative diabetes outcomes. The following reports were presented during the discussion: ‘Glycemic variability: clinical and prognostic value. Types of glycemic variability’ (Candidate of Medical Sciences, assistant Professor Zilov A.V.); ‘Methods of assessment of variability of glycemia in clinical trials and routine practice’ (PhD, Professor Markova T. N.); ‘Current international and national recommendations on glycemic monitoring’ (PhD, Professor Galstyan G. R.) and ‘Peculiarities of glycemic variability and its evaluation among children and adolescents’ (Candidate of Medical Sciences Vitebskaya A.V.).

Present literature review provides information about clinical trials that evaluated the association of the carriage of antithyroid antibodies (ATA) and the reduction of the ovarian reserve, as well as the effectiveness of assisted reproductive technologies. The ambiguity and sometimes the opposite of the conclusions of different authors, makes it possible to recommend a balanced attitude to the advisability of screening for ATA in women with a reproductive dysfunction as well as the therapeutic measures proposed in some guidelines based on the results of such examination.

Сахарный диабет и хронические заболевания печени. Обзор литературы (часть 2): особенности лечения Сахарный диабет (СД) и хронические заболевания печени (ХЗП) - патологические состояния, ассоциированные друг с другом и достигающие масштабов эпидемии. Существует сильная патогенетическая взаимосвязь нарушений углеводного обмена и ряда ХЗП. Описаны единые механизмы, провоцирующие метаболические и аутоиммунные нарушения при развитии различных ХЗП, приводящие к стеатозу, инсулинорезистентности (ИР), нарушению толерантности к глюкозе и развитию СД. Эффективный контроль гликемии может оказать благоприятное влияние на лечение этих пациентов, и наоборот - имеются данные о положительном влиянии терапии ХЗП на углеводный обмен. Рассматриваются вопросы коррекции углеводного обмена у пациентов с ХЗП, приведены основные группы современных сахароснижающих препаратов, механизмы их действия, влияние на физиологию печени, возможности использования каждой из этих фармакологических групп у пациентов с нарушенной функцией печени. Перечислены современные подходы и возможности медикаментозного воздействия на процесс фиброгенеза при ХЗП, влияние этих препаратов на углеводный обмен.