Tatiana Vasil'Evna Nikonova

Pneumococcal diseases are a relevant issue of the practical healthcare. The increase in pneumococcal infection in the Russian Federation in recent years, especially among persons over 60 years old, causes the need to improve prevention measures for this infection. The highest level of morbidity with pneumococcal infection is recorded in adults with various health problems (with comorbid conditions) — diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease. Vaccination, which is the only way to significantly influence morbidity, mortality and reduce the growth of antibiotic resistance, is recognized as an effective method of pneumococcal infection prevention. Vaccine prophylaxis is one of the priority areas for implementation of the national policy on development of the health system in Russia. Special niche in the preventive continuum is immunoprophylaxis in persons, especially over 60 years old, belonging to risk groups. Meeting of the Experts Council on the «Vaccination against pneumococcal infection as a mean to reduce morbidity and mortality of adult population at risk in the Russian Federation» topic has taken place in Moscow on February 11, 2025 under the chairmanship of the academician of the RAS O.M. Drapkina and under the auspices of the Russian Society of Non-communicable Diseases Prevention (RSNCDP). The session was attended by the chief consultants of the Ministry of Health of Russia, leading experts in the field of therapy, cardiology, pulmonology, endocrinology, rheumatology, gerontology, preventive medicine, epidemiology, microbiology and antimicrobial resistance, infectious diseases, an expert in pharmacoeconomic research, who presented relevant problems and proposals for their solution in the context of the discussed topic in their reports. The resolution of the Experts Council is presented in this article.

Background. Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in inflammatory processes by recruiting monocytes and macrophages to sites of inflammation. Inflammation is closely linked to poor control of diabetes mellitus (DM), characterized by significant glycemic fluctuations and prolonged hyperglycemia, as well as subclinical, low-grade inflammation of adipose tissue in type 2 DM. Elevated levels of MCP-1 have been associated with both type 1 and type 2 DM; however, data on its role in the pathogenesis of latent autoimmune diabetes in adults (LADA) are extremely limited. Aim. To evaluate MCP-1 levels and their association with glycemic control parameters in patients with different types of DM (type 1 DM, type 2 DM, and LADA). Materials and methods. Between February and November 2023, 80 individuals participated in the study, divided into four groups: patients with type 1 DM (n = 22), type 2 DM (n = 22), LADA (n = 14), and healthy volunteers (n = 22). The median ages were 26 years [21; 32] for type 1 DM, 41 years [33; 51] for type 2 DM, 41 years [33; 46] for LADA, and 33 years [26; 40] for healthy controls. Inclusion criteria were age between 18 and 55 years, body mass index up to 35 kg/m², and a diagnosis of one of the specified forms of DM. Exclusion criteria included other systemic autoimmune diseases, pancreatic diseases, and the use of immunosuppressive therapy. Results. MCP-1 levels were significantly higher in patients with type 1 DM (213 [162; 263] pg/ml) and type 2 DM (228 [168; 294] pg/ml) compared to healthy volunteers (174 [151; 207] pg/ml; p 0.05). Patients with LADA showed a non-significant trend toward elevated MCP-1 levels (218.51 [160; 268] pg/ml; p 0.05). ROC analysis indicated that MCP-1 is not suitable as an additional marker for the differential diagnosis of LADA. Conclusion. Elevated MCP-1 levels in patients with type 1 and type 2 DM suggest its possible involvement in the pathogenesis of these diabetes types. The lack of significant MCP-1 elevation in patients with LADA limits its utility as a diagnostic marker for this condition.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is considered an intermediate form between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying its unique clinical and pathogenetic features remain insufficiently studied. Identifying differentially expressed genes (DEGs) in LADA compared to T1DM is essential for developing more personalized diagnostic and therapeutic approaches.OBJECTIVE: To identify DEGs in peripheral blood mononuclear cells (PBMCs) of patients with LADA compared to those with T1DM, and to evaluate differences in DEGs between these patient groups and healthy volunteers.MATERIALS AND METHODS: The study included 60 participants (23 T1DM patients with disease duration of up to 1 year, 15 LADA patients with disease duration of up to 5 years, and 22 healthy volunteers). The median age of LADA patients was 40 [34; 45] years, and for T1DM patients, 26 [21; 31] years. This was a single-center, cross-sectional observational study. PBMCs were isolated from all participants, and single-cell RNA sequencing (scRNA-seq) was performed. Differential gene expression analysis was conducted using a pseudo-bulk approach (pyDEseq2, pRESULTS: In LADA patients, reduced expression of HLA-G, SPARC, and C20orf204 and increased expression of AC002460.2 were observed compared to healthy volunteers (pIFIT1, CASP3, LAMP3, HIST1H2BN). When comparing LADA to T1DM, only one transcript, C20orf204, showed statistically significant differential expression (pCONCLUSION: The findings indicate that LADA and T1DM share similar molecular patterns, with LADA exhibiting moderate changes in the expression of genes associated with immune regulation and inflammation. The minimal differences between these forms of diabetes highlight their pathogenetic similarity.

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.

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.

Dear Colleagues!We are glad to present the 11^th 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

Diabetes is disease of both the endo- and exocrine parts of the pancreas. Pancreatic exocrine insufficiency (PEI) can occur in every 2–3 patients with diabetes and affect not only the quality, but also life expectancy. At the same time, the diagnosis and treatment of PEI is not getting enough attention. The endocrinologist, as the main specialist leading patients with diabetes, can diagnose and treat patients with pancreatic exocrine insufficiency and diabetes using adequate doses of pancreatic enzyme replacement therapy (PERT).

The pancreas belongs to the glands of mixed secretion and simultaneously performs both endo- and exocrine functions. Exocrine pancreatic insufficiency (EPI) is the general name for the malabsorption process caused by inadequate production and decreased activation of the enzymes of the pancreas acinar cells, such as amylase, lipase and protease, which are necessary for digestion. The prevalence of EPI in patients with type 1 diabetes, according to many authors, varies from 25 to 59%, which is determine by the data of pancreatic elastase-1. In this work, we present a clinical case of confirmed exocrine pancreatic insufficiency in a patient with a 6-year history of type 1 diabetes, which became the main cause of the development of episodes of hypoglycemia after meals. In the course of further studies, antibodies to lactoferrin and a reduced prostate volume, determined by MRI data, high levels of antibodies to glutamate decarboxylase and zinc co-transporter 8, as well as residual insulin secretion based on the level of C-peptide on an empty stomach detected.

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

BACKGROUND: Observation of changes in the volume and size of the pancreas has a long history, however, the results of studies are still not unambiguous, the specific causes of changes in pancreatic volume, as well as their consequences, are not clear. According to some data, the decrease of pancreas volume in life expectancy is 35–45% in the population of patients with a long history of type 1 diabetes, and about 20–25% during the first year of the disease. Interestingly, in T1D in 20–45% of cases, the development of exocrine pancreatic insufficiency is noted, one of the manifestations of which is pancreatic atrophy, leading to a decrease in life expectancy.AIM: Assess the volume and size of the pancreas, as well as factors that can influence on their changes.MATERIALS AND METHODS: The study included 78 patients with type 1 diabetes mellitus, the control group consisted of 23 people without previously identified disorders of carbohydrate metabolism, comparable in age and anthropometric parameters with the study group. RESULTS: The volume and dimensions of the pancreas were statistically significantly less in patients with T1D than in the control group. In addition, the influence of the duration of T1D and the age of onset of the disease on these indicators has been proven.CONCLUSION: The volume and size of the pancreas in patients with T1D is less than in healthy individuals. It is necessary to study the effect of these changes on the function of the pancreas.