Dear Colleagues!We are glad to present the 11th Edition of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO), International Diabetes Federation (IDF), European Association for the Study of Diabetes (EASD), American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), International Society for Pediatric and Adolescent Diabetes (ISPAD) and Russian Association of Endocrinologists (RAE). Current edition of the “Standards” also integrates results of completed randomized clinical trials, as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 783 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 962 762 patients with DM in this country on 01.01.2023 (3,42% of population) with 92,3% (4 581 990) – Type 2 DM, 5,6% (277 092) – Type 1 DM and 2,1% (103 680) – other types of DM, including 8 758 women with gestational DM. However, these results underestimate real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that 54% of patients with Type 2 DM are undiagnosed. So real number of patients with DM in Russia is 11-12 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In accordance with the Federal Law № 489-FZ of 25.12.2018 medical care should be provided on the basis of the clinical recommendations. Therefore, clinical recommendations posted in the rubricator of the Ministry of Health of the Russian Federation (https://cr.minzdrav.gov.ru) being the priority.This edition of the Algorithms for Specialized Care for Patients with Diabetes Mellitus contains the main information from the clinical guidelines for the management of diabetes mellitus in adults and children (“Type 1 Diabetes in Children (2022)”, “Type 1 Diabetes in Adults (2022)”, “Type 2 diabetes mellitus in children (2021)”, “Type 2 diabetes mellitus in adults (2022)”), as well as the updated data.New information has been added about indications for using of antihyperglycemic drugs and their instructional restrictions; algorithm of treatment of type 2 diabetes mellitus has been updated; clarifications have been made on the range of glycemic control in pregnant women; information on the treatment of diabetic complications and the management of pediatric patients has been added. In 2023, Russian diabetology suffered an unbearable loss - Alexander Yuryevich Mayorov, who was the executive editor of the previous issues and an active participant of the work on all the previous editions of “Algorithms” from the moment they were founded, passed away. This publication is dedicated to the memory of Alexander Yuryevich, who was an example of the service to patients and medicine, a friend, teacher, mentor, generously sharing his knowledge and the sample of the execution of the medical duty to all of us. On behalf of the Working Group

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The course of difficult-to-classify types of diabetes mellitus (DM) (slowly developing immune-mediated DM of adults (LADA), monogenic forms of DM (MODY)) has common features with both type 1 DM (T1DM) and type 2 DM (T2DM), so often remain misdiagnosed. Errors in determining the type of diabetes lead to incorrect treatment tactics, which leads to poor glycemic control, the development of complications, a decrease in the patient's quality of life, and increased mortality. The key method for diagnosing MODY is sequencing of genes associated with this disease, and LADA is an immunological blood test in combination with the features of the clinical picture. However, the exact criteria for referring patients to these studies have not yet been determined. Performing these studies on all patients without exception with risk factors can lead to unjustified economic costs, and access to them is often difficult. In this regard, various automated algorithms have been developed based on statistical methods and machine learning (deep neural networks, “decision trees”, etc.) to identify patients for whom an in-depth examination is most justified. Among them are algorithms for the differential diagnosis of T1DM and T2DM, algorithms specializing in the diagnosis of only LADA or only MODY, only one algorithm is aimed at multiclass classification of patients with diabetes. One of the algorithms is widely used, aimed at diagnosing MODY in patients under the age of 35 years. However, existing algorithms have a number of disadvantages, such as: small sample size, exclusion of patients with MODY or older patients from the study, lack of verification of the diagnosis using appropriate studies, and the use of late complications of diabetes as parameters for diagnosis. Often the research team did not include practicing physicians. In addition, none of the algorithms are publicly available and have not been tested for patients in Russia. This manuscript presents an analysis of the main automated algorithms for the differential diagnosis of diabetes, developed in recent years.

Сахарный диабет 1 типа (СД1) у молодых взрослых может иметь нетипичное, медленное течение, при котором потребность в инсулинотерапии возникает лишь через несколько лет после дебюта заболевания. Данная форма СД была описана как латентный аутоиммунный диабет взрослых (latent autoimmune diabetes in adults, LADA), а в последней классификации ВОЗ как - медленно развивающийся иммуноопосредованный диабет взрослых. Медленные темпы аутоиммунного разрушения бета-клеток при LADА вызывают особый интерес для разработки возможностей модуляции аутоиммунного процесса. ЦЕЛЬ: оценить данные, представленные в литературе, и предложить оптимальный дизайн исследо- вания гетерогенности аутоиммунного сахарного диабета (СД) на основе секвенирования РНК одиночных клеток (scRNAseq). МАТЕРИАЛЫ И МЕТОДЫ: поиск информации осуществлялся в опубликованных источниках, пред- ставленных в поисковых системах PubMed, Google Scholar и других за последние 10 лет. Использованы медицинские предметные рубрики: LADA, diabetes mellitus type 1 and 2, immunology, genetic, treatment, RNA-Seq в различных комбинациях с применением логических операторов OR и AND. РЕЗУЛЬТАТЫ: ведущую роль в развитии аутоиммунного СД играют основные клетки адаптивного имму- нитета, Т (CD4+ и CD8+) и В (CD20+ и СD19+) лимфоциты. У пациентов с LADA количество аутореактивных CD8+Т-клеток, непосредственно повреждающих клетки в ткани поджелудочной железы, снижено по срав- нению с пациентами с СД1 типа, а активация CD4+Т-клеток ведет к рекрутированию преимущественно провоспалительных макрофагов М1 и усилению эффекта CD8+Т-клеток. По сравнению с пациентами с СД1, количество CD4+Т-клеток у пациентов с LADA снижено, но повышено относительно здоровых лиц. Анализ экспрессии в единичных периферических мононуклеарах крови (scRNAseq) при СД1 показал связь между высокой экспрессией интерлейкина-32, сероконверсией и прогрессированием до СД1, в основном, за счет активированных высокодифференцированных Т-клеток и NK-клеток. Показано наличие большого числа антигенпрезентирующих клеток и макрофагов в панкреатических островках при СД1. В опубликованных источниках, где изучали экспрессию генов одиночных клеток, информация пред- ставлена преимущественно в рамках СД1, объем литературных данных по LADA крайне ограничен. Часть работ посвящена изучению клеток панкреатических островков, полученных при аутопсии, как правило, использовано не более 10-15 образцов пациентов с СД1, другие работы акцентируются на профилировании рецепторов T- и B-клеток, однако результаты неоднозначны и трудны для интерпретации в связи с широким репертуаром последовательностей рецепторов и малым количеством образцов, в связи с чем перспек- тивным является изучение экспрессии генов в периферических мононуклеарах крови пациентов с LADA. ВЫВОДЫ: секвенирование РНК одиночных клеток является перспективным направлением изучения патогенеза аутоиммунного СД, что позволяет выявить ассоциации между профилем рецепторов на им- мунных клетках и активностью аутоиммунного процесса. Оптимальным дизайном исследования является сравнение пациентов с СД 1 и 2 типов и LADA с минимально возможной длительностью заболевания (до 1 года) между собой.

Latent autoimmune diabetes in adults (LADA) according to various sources is from 4 to 12% of all cases of type 2 diabetes mellitus (T2DM). Its uniqueness lies in the simultaneous combination of autoantibodies to β-cells (characteristic of T1DM) and the possibility of treatment with oral hypoglycemic drugs (characteristic of T2DM) for at least 6 months. This is based on the pathogenesis common for T1DM and T2DM — the presence of an autoimmune reaction with the simultaneous involvement of adaptive and innate immunity, as well as, to a lesser extent, insulin resistance and a number of components of the metabolic syndrome. LADA has more in common with T1DM — the same stages in the development of the disease, from genetic predisposition to the undoubted development of insulin dependence, the difference lies in the duration of each of the periods and the age of manifestation. LADA is characterized by an older age of manifestation of 30–35 years and a slower rate of destruction of β-cells. This article presents data on the diagnosis, progress of LADA, its similarities and differences with other types of DM, and immunological features. The article also analyzes the modern approach to the treatment of patients with LADA and promising methods of treatment. The search for information was processing in published sources attached to the search engines PubMed, Google Scholar, Scopus, Web of Science, eLibrary.ru over the past 10 years. The following medical subject headings were used: latent autoimmune diabetes in adults, diabetes mellitus type 1 and 2, immunology, pancreas, genetic, treatment in various combinations using OR and AND logical operators.

According to the decision of the WHO, therapeutic education (TE) of patients is an independent branch of medicine and an essential component of the treatment of chronic diseases, primarily diabetes mellitus and obesity. TE is implemented through the creation of “Schools for patients with diabetes mellitus” and “Schools for patients with overweight” (“Schools”) as a structural unit of a medical institution. On April 25–26, 2022, the First All-Russian Forum «Therapeutic Education in Endocrinology» was held online, organized by the Public Organization «Russian Association of Endocrinologists», which was attended by leading experts in this field. As a result of its work, this Resolution was adopted by the experts. It discusses the methodological and pedagogical foundations of TE, it is proposed to make changes related to the organization of the work of «Schools», tariffing in the obligatory health insurance system, and training of personnel, including nurses.

BACKGROUND: Russia is one of the most multinational states in the world. Identification of ethnic groups with a higher risk of developing DM2, analysis of risk factors for the development of DM2 will allow developing personalized approaches to the prevention and treatment of DM2.AIMS: To reveal ethnic features of the prevalence of carbohydrate metabolism disorders and risk factors for the development of DM2 in the adult population of the Russian Federation.MATERIALS AND METHODS. A retrospective analysis of the database of the national epidemiological cross-sectional study NATION was carried out. Depending on the self-specified nationality, on the basis of anthropological characteristics, the following ethnic groups were identified: “Mongoloid population”, “Peoples of the Volga region”, “Peoples of the North Caucasus”, “Peoples of Transcaucasia”, “Russians”. The analysis consisted of several stages and included: analysis of the anthropometric features of the selected groups, taking into account the presence of carbohydrate metabolism disorders (MO); study of the prevalence of violations of the MA in the selected ethnic groups; analysis of ethnic characteristics of risk factors for the development of type 2 diabetes; analysis of the frequency of violations of the MA in various ethnic groups, taking into account the territory of residence. MR disorders were defined as the presence of DM and/or prediabetes. In accordance with the WHO criteria, HbA1c≥6.5% corresponded to the diagnosis of DM, HbA1c values in the range of 5.7%≤HbA1c<6.5% to the diagnosis of prediabetes.RESULTS: The highest frequency of violations of the MA was observed in the group «Peoples of the Volga region» (31.2%), the lowest in the «Peoples of the North Caucasus» (15.6%). BMI in the group “Peoples of the Volga region” was significantly lower than in the group “Peoples of the North Caucasus. Violations of MR were more often observed in the abdominal nature of obesity, obesity of the 1st stage, age over 45 years in the groups «Mongoloid population» and «Peoples of the Volga region» than in the peoples of the «Northern Caucasus» and «Transcaucasia». The frequency of occurrence of SR violations among representatives of the Volga Peoples group living in their historical territories was higher than among Russians living in the same regions: 32.5% and 24.3% (p<0.001 χ2 criterion), and also higher than in the Russian CFD: 32.5% and 27.4%, respectively, p=0.001 (χ2 test). The prevalence of violations of the MA among the peoples of the North Caucasus was less than among the Russians of the Central Federal District — 13.9% and 27.36%, respectively (p<0.001 χ2 criterion). The prevalence of MR violations among representatives of the “Peoples of the North Caucasus” group living in their historical territories (n=598) was less than among those living in other regions of the Russian Federation (n=164) (13.9% and 21.95%, p= 0.012 criterion χ2).CONCLUSION: In the present work, for the first time, we analyzed the prevalence of MR disorders in various ethnic groups of the population of the Russian Federation, identified certain ethnic characteristics of DM2 risk factors and their contribution to the development of the disease. The obtained results should be used for planning preventive programs in various regions of the Russian Federation.

Introduction One of the stages of reproduction of SARS-CoV-2 is the S-protein glycosylation to facilitate penetration into target cells. It has been suggested that SARS-CoV-2 is able to enter erythrocytes, interact with heme and porphyrin, which could influence HbA1c levels. Assessment of HbA1c levels in individuals with acute COVID-19 and after recovery may show clinical relevance of this hypothesis. Aim To assess HbA1c levels in patients with COVID-19 in the acute phase and in early (6–8 weeks) and late (52±2 weeks) periods after recovery. Materials and methods We conducted a multicenter prospective study, which included patients hospitalized in Endocrinology Research Centre and the City Clinical Hospital № 52" diagnosed with COVID-19, virus identified/ not identified. Patients were divided into three groups according to baseline HbA1c level and the presence or absence of previous history of diabetes previous history of diabetes mellitus (DM): HbA1c ≤ 6.0%, HbA1c > 6.0% and patients with DM. Patients were examined during the acute COVID-19 phase and in early (6–8 weeks) and late (52±2 weeks) periods after recovery. Oral glucose tolerance test was performed in the group with initial HbA1c > 6.0% to clarify the diagnosis. Results We included 194 patients in the study. During the follow-up, 52 patients were examined in 6–8 week period: 7 with HbA1c ≤ 6.0%, 34 with HbA1c > 6.0%, 11—with previously diagnosed DM. Carbohydrate metabolism assessment in the later stages (52±2 weeks) after recovery was performed in 78 patients: 33 patients with HbA1c ≤ 6.0%, 36 patients with HbA1c > 6.0% and 9 patients with previously established diabetes. HbA1c median in patients with HbA1c ≤ 6.0% was 5.7% [5.3;5.8], with HbA1c>6.0% -6.4% [6.2; 6.6], with previously diagnosed DM—7.7% [7.2; 8.9]. Statistically significant decrease in HbA1c over time 6–8 weeks after extracts were obtained in both groups of individuals without a history of DM (Wilcoxon test, p<0.05). After 52±2 weeks we observed HbA1c decrease in all three groups (Fridman test, p<0.05): in patients with HbA1c ≤ 6.0% median HbA1c was 5.5[5.3;5.7], with HbA1c>6.0% - 6.1[6.15;6.54], with previously diagnosed DM—7.8 [5.83; 8.08]. Development of DM after 52±2 weeks was recorded in 7.24% of all examined patients without a history of DM, which is 16.6% of the total number of patients examined in dynamics with HbA1c > 6.0%. Conclusion HbA1c elevation during the acute phase of COVID-19 may be false due to the effect of SARS-CoV-2 on hemoglobin kinetics and/or detection on the surface of the SARS-CoV-2 virion highly glycosylated S-proteins by high performance liquid chromatography determinations. Upon detection HbA1c > 6.0% in patients with COVID-19 in the active phase of the disease without concomitant hyperglycemia re-determine the level of HbA1c after recovery is recommended.

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Group

клинический случай применения гликлазида мВ у пациента с сахарным диабетом 2 типаФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр эндокринологии» Министерства здравоохранения Российской Федерации, 117036, г.Москва, Российская Федерация Кононенко и.в., Смирнова о.М

Sulfonylureas are widely prescribed all over the world, mainly because of their high effectiveness. At the same time, the heterogeneity of the group is obvious, primarily in relation to the effect of drugs on the risk of developing hypoglycemic events. The review presents the results of new studies, including «Comparative effectiveness of gliclazide modified release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes» and results of a model-based meta-analysis of 24 antihyperglycemic drugs for type 2 diabetes, confirming the higher efficacy of modified release gliclazide (gliclazide MB) compared to DPP-4, as well as a low risk of hypoglycemic conditions. The results of recent studies, as well as the results of the ADVANCE and ADVANCE-ON studies, suggest that gliclazide MB is safe to use as a second-line drug, especially in patients with chronic kidney disease.

Introduction: COVID-19 can trigger either transient stress-induced state, or newly onset diabetes mellitus (DM). It is well known that HbA1c serves as an indicator of glycemic status 12 weeks before the acute disease. Aim: To examine glycemic status at admission and 6 weeks after hospital discharge in patients with confirmed COVID-19 but no previous DM-history. Methods: Of 155 patients hospitalized with COVID-19 and pneumonia 111 persons had no previous DM-history. The levels of HbA1с, fasting and admission plasma glucose (FPG and APG) were measured at admission and 6 weeks after the discharge. The severity of COVID-19 was confirmed by CT scan, SpO2, serum IL-6, CRP, D-dimer. Results: All 111 patients had normal FPG and APG values. According to HbA1c level all the patients were divided into two groups: A) HbA1c≤6.0% (n=64, median 5,8%) and B) HbA1c>6,0% (n=47, median 6,4%). Our particular interest was focused on the group B due to the discrepancy of high HbA1c level and normal FPG and APG. Group B patients were retested for glycemic status in 6±1 week after the discharge. Surprisingly the median HbA1c level dropped down from 6,4% to 5,7% in such a short period of time with no antidiabetic drugs. COVID-19 severity markers were significantly higher in the group B. Conclusions: We suggest two explanations for this faster than expected HbA1c decrease: 1) patients with HbA1c>6,0% will progress to DM later, and, therefore, a longer follow-up is needed; 2) SARS-CoV-2 virus has extensively glycosylated spike(S)-protein that may bind to erythrocytes. High-pressure liquid chromatography (the standard method for HbA1c) probably fails to separate the glycated 1-β-chain of hemoglobin from glycated viral spikes. In this case, abnormally high HbA1c in COVID-19 patients with no DM-history may serve as a marker of severe viral erythrocyte damage rather than a marker for the glucose control. This hypothesis is confirmed by the prompt (in 6 weeks) normalization of HbA1c level following the virus elimination. Disclosure M. V. Shestakova: None. I. Kononenko: None. Z. Kalmykova: None. A. Zheleznyakova: None. N. Mokrysheva: None. Funding Ministry of Science and Higher Education of the Russian Federation (075-15-2020-899)

The review focuses on the new WHO classification published in 2019. Unlike the previous classification, this classification does not recognize subtypes of T1DM and T2DM and offers new types of diabetes: “hybrid types of diabetes” and “unclassified diabetes”. This classification provides practical guidance to clinicians for assigning a type of diabetes to individuals and choose appropriate treatment (whether or not to start treatment with insulin), particularly at the time of diagnosis. This review presents the variety of forms of diabetes, the features of their clinical picture, and also emphasizes the importance of molecular genetic and immunological studies to identify types of diabetes and determine personalized therapy. The selection of “hybrid forms” of diabetes is due to the fact that the treatment of these types of diabetes has its own characteristics associated with the specific pathogenesis of diseases. However, it is obvious that further studies should relate to the study of the mechanisms of damage and decrease in the function of в-cells. Perhaps future classification systems and, as a consequence, personalized treatment will focus on various mechanisms of damage to β-cells.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, the development of which is mediated by both genetic disorders and various intracellular and extracellular molecular processes. One of the main pathogenetic mechanisms for the development of T2DM is a progressive decrease in the mass and functional reserve of β-cells, which largely determines the course of T2DM. The mechanisms of action of most sugar-lowering drugs are associated with increased secretion of insulin, so it is obvious that the effectiveness of the therapy will also largely depend on the functional state of β-cells. All this explains the great interest in studying the mechanisms of damage of β-cells in T2DM and factors that can accelerate this process, leading to their death and the development of a relative and then absolute insulin deficiency. The mechanisms of dysfunction β-cells in T2DM have not been studied much. This article provides an overview of the data of domestic and foreign literature of recent years on the molecular, intracellular features of various mechanisms of damage and death of β-cells in type 2 diabetes. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Progressive decrease in the weight and functional reserve of β-cells is one of the main pathogenetic mechanisms of development of type 2 diabetes mellitus (DM2). The rate of progression of these processes is strictly individual, which largely determines the course of DM2 and the effectiveness of the therapy. As a rule, apoptosis and necrosis are the main mechanisms of β-cell damage and death in CD2. At the same time, recent studies allow us to consider the destruction and death of β-cells as the outcome of other types of programmed cell death (PCG), the role of innate immunity in the Genesis of CD2 IS actively discussed. This article provides an overview of the data of domestic and foreign literature of recent years regarding the molecular, intracellular characteristics of different types of β-cell PCG in CD2. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, the development of which is mediated by both genetic disorders and various intracellular and extracellular molecular processes. One of the main pathogenetic mechanisms for the development of T2DM is a progressive decrease in the mass and functional reserve of β-cells, which largely determines the course of T2DM. The mechanisms of action of most sugar-lowering drugs are associated with increased secretion of insulin, so it is obvious that the effectiveness of the therapy will also largely depend on the functional state of β-cells. All this explains the great interest in studying the mechanisms of damage of β-cells in T2DM and factors that can accelerate this process, leading to their death and the development of a relative and then absolute insulin deficiency. The mechanisms of dysfunction β-cells in T2DM have not been studied much. This article provides an overview of the data of domestic and foreign literature of recent years on the molecular, intracellular features of various mechanisms of damage and death of β-cells in type 2 diabetes. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

Public organization “Russian Association of Endocrinologists”. Clinical guidlines.

BACKGROUND: Less than a year has passed since the start of the new coronavirus infection COVID-19 pandemic caused by SARS-CoV-2. First published research results demonstrate a frequent increase in glycemia in patients without previously diagnosed carbohydrate metabolism disorders. A possible relationship between the carbohydrate metabolism state and the course of COVID-19 is considered.AIM: To identify the incidence of known and newly diagnosed diabetes mellitus (DM) in hospitalized patients with COVID-19 and evaluate the relationship between glycated hemoglobin (HbA1c), inflammation markers and infectious disease severity.METHODS: A single-center, cross-sectional, retrospective study included 155 patients with confirmed COVID-19 and bi- lateral polysegmental viral pneumonia hospitalized in the Endocrinology Research Centre, Russian Federation. Diagnosis of carbohydrate metabolism disorders was based on the HbA1c level, blood glucose level at admission (BGA) and fasting plasma glucose (FPG). Patients were divided into 2 groups: without the previously diagnosed DM (n=129, 83.3%) and with known history of DM (n=26, 16,7%). Patients without previously diagnosed DM were divided into subgroups according to HbA1c levels: ≤6,0% (Group A), >6,0% HbA1c, <6.5% (Group B), ≥6,5% (Group C). Additionally, insulin, interleukin 6 (IL-6) and D-dimer levels were measured in all patients. Blood oxygen saturation (SpO2) was measured by pulsoximetry, computerized tomography of lungs with calculation of lung parenchyma damage percentage.RESULTS: Type 2 DM was previously established in 16.7% of all included patients. Among patients without DM history, DM was revealed in 8 patients (5.2%), based on HbA1c, FPG and BGA. In 66 patients (42.6%) we observed no changes in carbohydrate metabolism. In 55 patients, the interpretation of carbohydrate metabolism state was difficult due to inconsistency of HbA1c level with FPG and BGA: in particular, the level of HbA1c ≥ 6.5% (which corresponds to the diagnostic threshold of the DM) was detected in 19 patients (12,2%) with normal FPG and BGA. No true stress hyperglycemia on admission and according to FPG was reported. Despite the presence of confirmed DM, HbA1c levels positively correlated with inflammatory markers (erythro- cyte sedimentation rate, C-reactive protein, IL-6) and SpO2. Patients with a HbA1c ≥6.5% without DM history had the most severe course of the disease: longest duration of hospitalization, largest damage of the pulmonary tissue, and high lethality.CONCLUSION: The incidence of DM among patients hospitalized with COVID-19 was 21.9% (16.7% had previous diagnosis of DM, 5.2% — newly diagnosed), which is 1.5 times higher than in general population in a comparable age category. It is difficult to assess the carbohydrate metabolism disorders in patients in acute infectious period. An increased level of HbA1c (≥6.5%), first detected in the acute period of infection, in combination with normal FPG and BGA parameters, cannot be a diagnostic criterion and requires dynamic monitoring. HbA1c level can be considered as a predictive factor of COVID-19 severity, independent of DM.