Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

Более 30 лет назад Ludwig J. (1980) описал заболева-ние, сходное с алкогольным стеатогепатитом, у пациентов с сахарным диабетом (СД), не употребляющих алкоголь, и назвал данное заболевание неалкогольным стеатогепа-титом (НАСГ) [1]. Неалкогольная жировая болезнь печени (НАЖБП) является самым распространенным хроническим заболеванием печени и приняла масштаб эпидемии, так же как ожирение и СД 2 типа (СД2) [2]. НАЖБП включает в себя спектр заболеваний от жирового гепатоза без признаков воспаления до НАСГ, цирроза печени и гепатоцеллюляр-ной карциномы [3]. ЭПИДЕМИОЛОГИЯОписанная распространенность НАЖБП широ-ко варьирует в зависимости от изучаемой популяции и от используе мого метода диагностики. Распространен-ность гистологически подтвержденной НАЖБП состав-ляет от 20 до 51%, однако, по данным ультразвукового метода исследования, НАЖБП встречается реже, от 17 до 46% [4] Неалкогольная жировая болезнь печени (НАЖБП) и сахарный диабет 2 типа (СД2) -патологические состояния, ассоцииро-ванные друг с другом и достигающие размеров эпидемии. Одним из наиболее значимых факторов риска развития как СД2, так и НАЖБП является ожирение, которое усиливает имеющуюся инсулинорезистентность (ИР). Последняя является ос-новным патогенетическим звеном СД2 и НАЖБП, связывая эти два патологических состояния. В настоящее время повышен интерес к поиску неинвазивных методик исследования; для оценки фиброза и определения показаний для биопсии печени неинвазивным методом используется Шкала оценки стадии фиброза при НАЖБП (NAFLD fibrosis score), расширенная панель фиброза печени (ELF) и транзиентная эластография. Однако золотым стандартом диагностики остается биопсия печени. Ввиду того, что у пациентов с СД чаще выявляется НАЖБП, чем в общей популяции, а также учитывая, что наличие СД явля-ется фактором риска прогрессии НАЖБП, данная когорта пациентов должна находиться под более тщательным контролем клиницистов. Данная обзорная работа посвящена поиску причинно-следственных связей таких коморбидных заболеваний, как НАЖБП и различные нарушения углеводного обмена, а также приоритетным направлениям диагностики НАЖБП.КЛЮЧЕВЫЕ СЛОВА: инсулинорезистентность; сахарный диабет; неалкогольная жировая болезнь печени; неалкогольный стеатогепатит; ожирение NONALCOHOLIC FATTY LIVER DISEASE: CAUSE OR CONSEQUENCE OF INSULIN RESISTANCE?© Ekaterina E. Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are pathological conditions that are co-occurring, and have been reaching epidemic proportions. One of the most significant risk factors for the development of both T2DM and NAFLD is obesity, which increases existing insulin resistance (IR). IR thought to be one of the main pathogenic causes linking T2DM and NAFLD. In recent years, there has been increased interest in obtaining non-invasive methods for assessing fibrosis and determining indications for liver biopsy, such as the NAFLD fibrosis score, extended liver fibrosis panel, and transient elastography. However, liver biopsy remains the gold standard for diagnosing NAFLD. Given that pa...

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: 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 (HbA1c) 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 HbA1c 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 HbA1c analysis (77,4% and 36,5% accordingly). Amount of false negative results in FBG test in 3 times more often occurred in comparison with HbA1c. HbA1c test in 3 times more precisely than FBG test for carbon metabolism abnormalities detection. Diagnostic in time with HbA1c 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 HbA1c performing instead FBG test. CONCLUSION: HbA1c 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 HbA1c test in comparison with late diagnostics in case of FBG test execution.

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 201316. Materials and methods: The database of the Russian Federal Diabetes register (81 regions). The indicators of coma for 201316 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 04.2/10000 adults. The frequency of new cases of coma has a tendency to decrease: 0,90,4/10000 adults: T1D 5.73.4, T2D 0.60.2/10000 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 3.89.1 years, with T2D 3.57.0 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 didnt 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 201316 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.

Approximately 90% of all cases of diabetes mellitus in adults involve type 2 diabetes, while the prevalence of maturity-onset diabetes of the young (MODY) remains undetermined leading to inappropriate treatment regimens. One of the most common monogenic forms of diabetes is a disease caused by a mutation in the glucokinase gene, MODY2. Knowledge of the clinical features of the disease allows the selection of patients with a high risk of mutation in the glucokinase gene and verification of diagnosis for molecular genetic research. This paper reflects the clinical features of MODY2 and the difficulties of diagnosis in adults. Furthermore, it presents a clinical case of a patient with MODY2 demonstrating all the features of this type of diabetes. A family member with a mutation in the gene allows to predict the nature of carbohydrate metabolism disorders in first degree relatives. A targeted study of only one part of the glucokinase gene in molecular genetic research is sufficient to confirm the diagnosis in relatives.

Обучение и психосоциальные аспекты

Неалкогольная жировая болезнь печени (НАЖБП) -ассоциированная с ожирением группа патологических изменений [1], характеризующихся аномальным нако-плением липидов в гепатоцитах в отсутствие хрониче-ского употребления алкоголя в гепатотоксических до-зах (более 40 мг в день для мужчин и более 20 мг в день для женщин при ежедневном употреблении). Наличие НАЖБП ассоциируется с развитием инсулинорезистент-ности, метаболического синдрома и сахарного диабета 2 типа (СД2), а также риском развития фиброза и цир-роза печени с возможным исходом в печеночно-кле-точный рак. В развитых странах НАЖБП затрагивает до 30-40% населения и является наиболее частой пато-логией печени, встречающейся в клинической практи-ке [2]. Одним из возможных путей лечения этого заболе-вания является модуляция активности фарнезоидного рецептора (FXR), являющегося ключевым регулятором метаболизма липидов и глюкозы. Настоящий обзор посвящен молекулярным аспектам НАЖБП, роли FXR в биологии этого заболевания и перспективам исполь-зования модуляторов FXR для терапии НАЖБП и ассоци-ированных с ней состояний, таких как метаболический синдром и СД2. Неалкогольная жировая болезнь печени (НАЖБП) представляет собой группу связанных с ожирением патологиче-ских изменений, характеризующихся аномальным накоплением липидов в клетках паренхимы печени. НАЖБП и раз-личные ассоциированные с ней состояния, такие как резистентность к инсулину и сахарный диабет 2 типа (СД2), а также возможные риски развития фиброза и цирроза печени с потенциальным исходом в печеночно-клеточный рак представляют собой первостепенные проблемы здравоохранения в развитых странах, постепенно вытесняя по значимости аналогичные патологии, вызываемые регулярным употреблением гепатотоксических доз алкоголь-ных напитков. Фундаментальные и клинические исследования последних лет продемонстрировали важную роль фарнезоидного рецептора (FXR, NR1H4) в регуляции метаболизма глюкозы, липидов и желчных кислот. Настоящий обзор посвящен молекулярным аспектам патогенеза НАЖБП, роли FXR (NR1H4) в биологии этого заболевания, а так-же перспективам использования различных (в том числе разнонаправленных) модуляторов действия FXR (NR1H4) для терапии НАЖБП и ассоциированных с ней состояний, таких как метаболический синдром и СД2, а также других заболеваний, в патогенезе которых играет роль FXR (NR1H4).КЛЮЧЕВЫЕ СЛОВА: неалкогольная жировая болезнь печени; неалкогольный стеатогепатит; фарнезоидный рецептор Nonalcoholic fatty liver disease (NAFLD) is a group of obesity-associated pathological changes characterized by abnormal accumulation of lipids in cells of the liver parenchyma. NAFLD and associated conditions, namely insulin resistance and type II diabetes mellitus (DM2), as well as the possible risks of developing fibrosis and cirrhosis with a potential outcome in hepatocellular carcinoma, represent the primary health problems in developed countries, gradually replacing the importance of similar pathologies caused by the regular use of hepatotoxic doses of alcoholic beverages. Recent fundamental and clinical studies...