Irina V. Kononenko

Relevance. Excessive nutrition is considered one of the risk factors for the development of T2DM. In this regard, the question arises whether the nutritional characteristics of certain peoples can explain the differences in the prevalence of T2DM. Objective: To study the nutritional characteristics of four ethnic groups of the Russian population that differ in the prevalence of T2DM — Yakuts, Tatars, Bashkirs and Chechens — and to identify nutritional factors that may be associated with a higher prevalence of T2DM. Materials and methods: The pilot study included healthy individuals of four ethnic groups. Based on the developed questionnaire, the frequency of consumption (“daily”, “once a week or more”, “less than once a week”, “I do not consume”) of the main food groups was assessed: “meat products, including poultry” (meat), “fish and seafood”, “eggs”, “dairy products”, “bread and bakery products”, “pasta”, “porridge, cereals, rice”, “potatoes”, “vegetables”, “fruits”, “sweets, chocolate”, “confectionery”, “sweet carbonated drinks”. The results of the study as a whole indicate the “universality of the food basket”. At the same time, the obtained data indirectly indicate a more caloric diet, rich in animal products, among ethnic groups with a high prevalence of type 2 diabetes — Yakuts and Tatars, while the diet of Chechens, the ethnic group with the lowest prevalence of type 2 diabetes, characterized by a higher consumption of fruits and vegetables. Conclusion: The results of the pilot project made it possible to identify nutritional characteristics in the studied ethnic groups that may influence the risk of developing type 2 diabetes and should be take into account when developing measures to prevent carbohydrate metabolism disorders and obesity.

These guidelines present an algorithm for managing patients with obesity and noncommunicable diseases in primary health care facilities. The presented algorithm includes measures aimed at assessing the patient's condition and comorbidities, developing individualized treatment plans and adjusting therapy, and regularly monitoring the therapy effectiveness. Key criteria for monitoring treatment effectiveness are presented to reduce the risk of complications and improve the overall quality of life and life expectancy of patients. The systematization and structuring of modern clinical guidelines and standards in terms of monitoring make this manual relevant, practice-­oriented, and useful for healthcare professionals. The inclusion of research data ensures the high effectiveness of the proposed approaches and their application in routine health practice. These guidelines can be used by healthcare administrators, heads of primary care facilities and related departments.

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. To investigate the heterogeneity of autoimmune diabetes mellitus (DM) in adults and identify factors associated with delayed initiation of insulin therapy in real-world clinical practice.MATERIALS AND METHODS. A retrospective analysis was conducted on clinical and laboratory data from 717 patients with DM onset after the age of 18 who were tested for antibodies against β-cell antigens (GAD, IA-2, ICA, ZnT8, insulin) at the National Medical Research Center for Endocrinology (NMRCE) between 2017 and 2022. Data were obtained from the electronic medical records of the NMRCE database and questionnaires from the nationwide clinical and epidemiological diabetes monitoring system in the Russian Federation. Patients with elevated vs normal antibody titers were compared, as well as patients with autoimmune DM based on the timing of insulin therapy initiation.RESULTS. Elevated antibodies to β-cell antigens were identified in 370 patients (51.6%). A combination of two or more antibodies at DM onset was found in 63.7% of cases. The most frequently elevated antibodies were ZnT8, GAD, and IA-2. There was no significant difference in age at onset between patients with positive and negative antibodies; however, those with positive antibodies had lower body mass index (BMI), a higher incidence of ketoacidosis, and lower levels of C-peptide, uric acid, and triglycerides at disease onset. Among antibody-positive patients, 36.8% did not require insulin therapy until at least 6 months after disease onset (median: 2 [1; 3] years). During onset and the first 5 years, these patients demonstrated higher BMI, triglycerides, and C-peptide levels. Notably, 8.9% of patients with elevated antibodies were managed exclusively with oral glucose-lowering agents and/or glucagon like peptide 1 (GLP-1) receptor agonists for a median of 3 [2; 7.5] years after disease onset, maintaining an HbA1c level of 6.7 [6.2; 7.75]%.CONCLUSION. Autoimmune DM in adults demonstrates heterogeneity in the rate of β-cell function decline and the development of insulin dependence. Later initiation of insulin therapy in autoimmune DM is associated with older age at onset, higher BMI, triglycerides, and C-peptide levels at diagnosis and during follow-up. The use of oral antidiabetic drugs and/or GLP-1 receptor agonists may be considered for patients with preserved C-peptide levels, provided that carbohydrate metabolism and C-peptide levels are regularly monitored. Nonetheless, insulin replacement therapy remains the primary pathogenetic treatment for autoimmune DM.

BACKGROUND: Molecular genetic testing (MGT) is increasingly accessible, improving diagnosis of monogenic diabetes (DM), particularly maturity-onset diabetes of the young (MODY). While most MODY research focuses on pediatric populations, diagnosis is possible after age 18. The Federal Diabetes Registry (FDR) offers unique insights into real-world management of MODY patients.AIM: To analyze the clinical features of DM onset, carbohydrate metabolism, complications, and hypoglycemic therapy (HT) in patients with the main types of MODY based on the FDR data.MATERIALS AND METHODS: A cross-sectional analysis of the FDR was conducted. All patients with registered MODY diagnoses (MODY-1, MODY-2, MODY-3, or other) as of June 1, 2023, were included. The specified MODY type was considered indicative of prior MGT. Direct MGT results are not recorded in the FDR.RESULTS: The study included 640 patients. MODY2 was the most prevalent type (69.4%), followed by MODY1 (18.2%) and MODY3 (12.4%). The median age of DM diagnosis was 19 years for MODY1, 10 years for MODY2, and 14 years for MODY3. The majority of patients (71.4%) were diagnosed with MODY before the age of 18 years.While 61% of MODY2 patients received monotherapy with diet, others received various ADT. Sulfonylureas were commonly prescribed for MODY3 patients (45.8%), and for a smaller portion of MODY1 patients (14.1%). Insulin therapy was more frequent in MODY1 and 3 (35.9% and 31.2%, respectively). The target glycated hemoglobin level was achieved in 82% of MODY2 patients and in 50.7% and 52.9% of MODY1 and 3 patients, respectively.Diabetic complications were observed in 6.04% of MODY2 patients, 23.0% of MODY1 patients, and 22.0% of MODY3 patients. Specific complications included diabetic retinopathy (5.75%, 1.21%, and 3.39% in MODY1, MODY2, and MODY3, respectively), diabetic nephropathy (10.3%, 2.11%, and 11.9%), and diabetic polyneuropathy (14.9%, 4.53%, and 15.3%).CONCLUSION: The FDR analysis revealed real-world practice patterns in MODY management, highlighting a lack of standardized treatment approaches and potentially unnecessary insulin use. These findings, coupled with an expected rise in MODY diagnoses, underscore the need for clinical guidelines for this population.

Dipeptidyl peptidase type 4 (DPP-4) inhibitors hold leadership positions in the treatment of type 2 diabetes worldwide due to their pathogenetically substantiated mechanism of action, low risk of hypoglycemic states and good tolerability. Today, they represent the largest class of glucose-lowering medicines. Sitagliptin, the first antidiabetic agent from this class, is the best known one and along with that remains the most promising medicine. It can be prescribed either as the initial treatment or later in a combination with other classes of hypoglycemic drugs, including sulfonylurea derivatives. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP), which blood concentrations increase under the effect of DPP-4 inhibitors, enhance glucose-stimulated insulin secretion through activating the cyclic adenosine monophosphate (cAMP) signaling pathway in pancreatic β-cells, meanwhile cAMP plays a critical role in an increase in β-cell sensitivity to glucose. Sitagliptin is an antidiabetic agent with significant data on cardiovascular safety. The efficacy of the drug is broadly similar to that of sulfonylurea derivatives. At the same time, the low risk of hypoglycemic states and the absence of side effects create certain advantages of using this drug in elderly patients. Active use of the drug in patients with diabetes in Japan is associated with the predominance of secretory disorders in the pathogenesis of the disease and the efficacy of DPP inhibitors in this ethnic group. The pleiotropic properties of the drug continue to be studied. The positive effects of sitagliptin in coronavirus infection may be associated with the anti-inflammatory and immunomodulatory properties of the drug. The potential of the drug in the treatment of immune-mediated conditions, as well as its neuroprotective properties in the prevention and treatment of Alzheimer's disease, are considered.

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