Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of 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), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). 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, 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 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 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 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) Type 2 DM, 6% (256 202) Type 1 DM and 2% (89 870) other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they dont receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary 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 the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. 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. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Group

BackgroundThe association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes.MethodsThe study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively.ResultsThe analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function.ConclusionIn the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

2. ДИАГНОСТИКА ЗАБОЛЕВАНИЯ ИЛИ СОСТОЯНИЯ (ГРУППЫ ЗАБОЛЕВАНИЙ ИЛИ СОСТОЯНИЙ), МЕДИЦИНСКИЕ ПОКАЗАНИЯ И ПРОТИВОПОКАЗАНИЯ К ПРИМЕНЕНИЮ МЕТОДОВ ДИАГНОСТИКИ 2.1 ЖАЛОБЫ И АНАМНЕЗ 2.2 ФИЗИКАЛЬНОЕ ОБСЛЕДОВАНИЕ 2.3 ЛАБОРАТОРНЫЕ ДИАГНОСТИЧЕСКИЕ ИССЛЕДОВАНИЯ 2.4 ИНСТРУМЕНТАЛЬНЫЕ ДИАГНОСТИЧЕСКИЕ ИССЛЕДОВАНИЯ 2.5 ИНЫЕ ДИАГНОСТИЧЕСКИЕ ИССЛЕДОВАНИЯ 3. ЛЕЧЕНИЕ, ВКЛЮЧАЯ МЕДИКАМЕНТОЗНУЮ И НЕМЕДИКАМЕНТОЗНУЮ ТЕРАПИИ, ДИЕТОТЕРАПИЮ, ОБЕЗБОЛИВАНИЕ, МЕДИЦИНСКИЕ ПОКАЗАНИЯ И ПРОТИВОПОКАЗАНИЯ К ПРИМЕНЕНИЮ МЕТОДОВ ЛЕЧЕНИЯ 3.1 ТЕРАПЕВТИЧЕСКИЕ ЦЕЛИ 3.1.1 Показатели контроля углеводного обмена (индивидуальные цели лечения) 3.1.2 Целевые уровни показателей липидного обмена 3.1.3 Целевые уровни показателей артериального давления 3.2 КОНТРОЛЬ УРОВНЯ ГЛЮКОЗЫ 3.3 НЕМЕДИКАМЕНТОЗНЫЕ МЕТОДЫ ЛЕЧЕНИЯ 3.3.1 Рекомендации по питанию 3.3.2 Рекомендации по физической активности 3.4 МЕДИКАМЕНТОЗНАЯ ТЕРАПИЯ 3.4.1 Общие принципы медикаментозной терапии 3.4.2 Инсулинотерапия 3.5 ХИРУРГИЧЕСКОЕ ЛЕЧЕНИЕ

Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of 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), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). 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, 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 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 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 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) Type 2 DM, 6% (256 202) Type 1 DM and 2% (89 870) other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they dont receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary 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 the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. 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. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Group

Значение результатов полногеномных исследований для первичной профилактики сахарного диабета 2 типа и его осложнений. Персонализированный подход Дедов И.И., Смирнова О.М., Кононенко И.В. ФГБУ Эндокринологический научный центр

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.

Влияние компенсации углеводного обмена и вида гипогликемизирующей терапии на исходы эндоваскулярных вмешательств у больных сахарным диабетом 2 типа Мичурова М.С., Кононенко И.В., Смирнова О.М., Калашников В.Ю. ФГБУ Эндокринологический научный центр, Москва (директор -академик РАН и РАМН И.И. Дедов) Появление в клинической практике методик чрескожных коронарных вмешательств с применением стентов, выделяющих лекарство, открыло новые возможности в лечении ишемической болезни сердца у больных сахарным диабетом. Однако, несмотря на это, больные сахарным диабетом имеют более высокий уровень смертности, частоты инфаркта миокарда; у них чаще возникает необходимость повторной реваскуляризации целевого сосуда, чем у пациентов без сахарного диабета. В данной статье обсуждаются возможные механизмы влияния компенсации углеводного обмена и характера гипогликемизирующей терапии на исходы чрескожных коронарных вмешательств. Ключевые слова: сахарный диабет 2 типа; ишемическая болезнь сердца; чрескожные коронарные вмешательства Introduction of drug-eluting stents for percutaneous coronary interventions opened novel options for treating coronary heart disease (CHD) in patients with diabetes mellitus. However, mortality and myocardial infarction rates are still higher among diabetes patients. They also require repeated revascularization of the target vessel more often than euglycemic individuals do. Current review discusses possible effects of diabetes compensation by various classes of antihyperglycemic agents on endovascular intervention outcomes.

Кардиология дним из мощных факторов повреждения органов и тканей при сахарном диабете (СД) считается гипергликемия, которая способствует неконтро-лируемой активации факторов роста фибробластов и маркеров воспаления. Совокупность всех патологических процессов приводит к активной перестройке соединитель-Изучение роли факторов роста фибробластов (bFGF, TGFβ1), маркеров воспаления (IL-6, TNF-α, СRP) и конечных продуктов гликирования (AGE, RAGE) у пациентов с ишемической болезнью сердца и сахарным диабетом 2 типа Иванникова Е.В., Мелкозёров К.В., Калашников В.Ю., Терёхин С.А., Кононенко И.В., Смирнова О.М. ФГБУ Эндокринологический научный центр, Москва (директор -академик РАН и РАМН И.И. Дедов) Цель. Определение уровня трансформирующего фактора роста фибробластов (TGFβ1), основного фактора роста фибробластов (bFGF), маркеров неспецифической воспалительной реакции (интерлейкина-6 (IL-6), фактора некроза опухолиальфа (TNF-α), С-реактивного белка (C-reactive protein (СRP)) и их взаимосвязи с конечными продуктами гликирования у больных с ишемической болезнью сердца (ИБС) в зависимости от компенсации углеводного обмена. Материалы и методы. У 87 пациентов с ИБС было проведено общеклиническое обследование, анализ показателей углеводного и липидного обмена, функции почек, а также эхокардиография и коронароангиография. Для определения уровня исследуемых показателей всем больным забор крови осуществлялся из аорты во время проведения коронароангиографии и параллельно из кубитальной вены. Результаты. Установлено, что наличие сахарного диабета (СД) у больных ИБС приводит к достоверному повышению уровня TGFβ1, IL-6, СRP в артериальной и венозной крови. Была получена прямая корреляция TGFβ1 с показателями липидного обмена. Выявлена прямая корреляционная взаимосвязь между степенью поражения коронарных сосудов и уровнем провоспалительных факторов и конечных продуктов гликирования в зависимости от наличия СД. Заключение. Полученные данные подтверждают наличие взаимосвязи нарушений со стороны соединительной ткани и липидного обмена в патогенезе атеросклероза. Ключевые слова: факторы роста фибробластов; сахарный диабет; ишемическая болезнь сердца bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP) and advanced glycation end-products (AGE, RAGE) in patients with ischemic heart disease and type 2 diabetes mellitus Ivannikova E.V., Melkozerov K.V., Kalashnikov V.Yu., Terekhin S.A., Kononenko I.V., Smirnova O.M. Endocrinology Research Centre, Moscow, Russian FederationAims. To evaluate plasma levels of transforming growth factor beta (TGFβ1), basic fibroblast growth factor (bFGF), markers for nonspecific inflammatory process (interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP)) and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD). Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standard clinical examination, including laboratory assessment of glycemic...