Gliflozins are a relatively new class of oral antihyperglycemic drugs that are increasingly being introduced into routine practice in the treatment of patients with type 2 diabetes mellitus (DM2). The hypoglycemic effect of gliflozins is associated with the stimulation of glucosuria, however, in addition to a pronounced hypoglycemic effect and high safety, these drugs also have many pleiotropic properties, due to the presence of many direct and indirect points of application. The purpose of this paper is to provide an overview of the currently best studied neuroprotective effects of this class of drugs. As materials in the course of the work, studies of foreign colleagues published in the period 2008–2022 were used. Analysis of the works showed that the neuroprotective effect of gliflozins is associated with many different mechanisms. Thus, gliflozins realize an anti-inflammatory effect by activating the M2 subpopulation of macrophages, reducing pro-inflammatory neurotransmitters (related primarily to the inflammasome). In addition, by reducing the activity of the mTOR signaling pathway, the drugs reduce the amount of beta-amyloid and improve neurotransmission. A group of works also showed the antiacetylcholinesterase effect of gliflozins, not to mention the decrease in the intensity of non-enzymatic protein glycation and insulin resistance. All of the above mechanisms provide an anti-inflammatory, anti-atherogenic effect, improve cognitive abilities in patients, reduce the frequency of hemorrhagic stroke, and can also potentially improve prognosis in patients with Alzheimer’s disease (AD). The effects described above were obtained during preclinical trials and many experimental studies, and some effects have already demonstrated their consistency in prospective clinical trials. However, the data obtained are still insufficient to form clear indications for this class of drugs in neurology, so the topic requires further study and clinical trials.
Over the past 10 years of studying the complications of type 2 diabetes mellitus (DM) and ways to deal with them, significant progress has been made in one of the most important areas of treatment — the prevention of cardiovascular and renal complications. Thus, when using inhibitors of type 2 sodium-glucose cotransporter, a significant reduction in the risks of cardiovascular mortality and progression of chronic heart failure, which occupy the main place in the structure of mortality in this cohort of patients, as well as a positive effect on diabetic nephropathy, one of the most common complications of type 2 diabetes, has been proven. However, there are other complications that significantly affect the duration and quality of life of patients. In particular, these include stroke, which occupies the 2nd-3rd place in the frequency of death of people with type 2 diabetes, and albuminuria, a frequent manifestation of diabetic kidney disease, which is associated with an increased risk of cardiovascular complications (including stroke) and chronic renal failure. Recent studies indicate the important role of sodium-glucose cotransporter type 1 in the development of these complications. Canagliflozin has the highest affinity for these transporters among iSGLT-2 registered in the Russian Federation. This article aims to evaluate the mechanisms of action of canagliflozin and its possible role in the prevention of stroke and albuminuria.
In 1838 G. Rees, a doctor from London (Guy's Hospital), for the first time isolated excess sugar from the blood serum of a patient with diabetes mellitus. Diagnosis of diabetes mellitus gradually developed. The next step was the understanding that regular monitoring of glucose levels by the patient himself is an integral part of diabetes mellitus therapy. The starting point of the technology for self-monitoring of diabetes mellitus was the determination of the sugar content in urine using chemical reactions. The method had no great clinical significance, it only indicated a progressive disease. The first Dextrostix blood glucose test strip (Ames-Mile's laboratories) was introduced in 1964. In 1970, the first automated blood glucose analysis system, the Ames Reflectance Meter (ARM), was created. Over time, the technology has been improved, accuracy, visibility, comfort, and an individual approach to glucometry have been formed. A new chapter was the development of remote technologies and the possibility of remote monitoring. More advanced data processing is now available in tabular and graphical form, with the calculation of 7-, 14-, 30-, and 90-day average glycemic values. A promising direction is the introduction of artificial intelligence in the management of diabetes mellitus.
Background Guidelines from 2016 onwards recommend early use of SGLT2i or GLP-1 RA for patients with type 2 diabetes (T2D) and cardiovascular disease (CVD), to reduce CV events and mortality. Many eligible patients are not treated accordingly, although data are lacking for Central and Eastern Europe (CEE). Methods The CORDIALLY non-interventional study evaluated the real-world characteristics, modern antidiabetic treatment patterns, and the prevalence of CVD and chronic kidney disease (CKD) in adults with T2D at nonhospital-based practices in CEE. Data were retrospectively collated by medical chart review for patients initiating empagliflozin, another SGLT2i, DPP4i, or GLP-1 RA in autumn 2018. All data were analysed cross-sectionally, except for discontinuations assessed 1 year ± 2 months after initiation. Results Patients (N = 4055) were enrolled by diabetologists (56.7%), endocrinologists (40.7%), or cardiologists (2.5%). Empagliflozin (48.5%) was the most prescribed medication among SGLT2i, DPP4i, and GLP-1 RA; > 3 times more patients were prescribed empagliflozin than other SGLT2i (10 times more by cardiologists). Overall, 36.6% of patients had diagnosed CVD. Despite guidelines recommending SGLT2i or GLP-1 RA, 26.8% of patients with CVD received DPP4i. Patients initiating DPP4i were older (mean 66.4 years) than with SGLT2i (62.4 years) or GLP-1 RA (58.3 years). CKD prevalence differed by physician assessment (14.5%) or based on eGFR and UACR (27.9%). Many patients with CKD (≥ 41%) received DPP4i, despite guidelines recommending SGLT2is owing to their renal benefits. 1 year ± 2-months after initiation, 10.0% (7.9–12.3%) of patients had discontinued study medication: 23.7–45.0% due to ‘financial burden of co-payment’, 0–1.9% due to adverse events (no patients discontinued DPP4i due to adverse events). Treatment guidelines were ‘highly relevant’ for a greater proportion of cardiologists (79.4%) and endocrinologists (72.9%) than diabetologists (56.9%), and ≤ 20% of physicians consulted other physicians when choosing and discontinuing treatments. Conclusions In CORDIALLY, significant proportions of patients with T2D and CVD/CKD who initiated modern antidiabetic medication in CEE in autumn 2018 were not treated with cardioprotective T2D medications. Use of DPP4i instead of SGLT2i or GLP-1 RA may be related to lack of affordable access, the perceived safety of these medications, lack of adherence to the latest treatment guidelines, and lack of collaboration between physicians. Thus, many patients with T2D and comorbidities may develop preventable complications or die prematurely. Trial registration NCT03807440.
Despite modern advances in diabetology, diabetes is a progressive non-communicable disease with the possible development of vascular complications, which is a global health problem. Therefore, maintaining optimal glycemic control is important for managing diabetes and preventing the development of acute and chronic complications of the disease. One of the parameters for assessing glycemic control is the indicator of time in the target range (Time in range TIR), calculated on the basis of data from continuous glucose monitoring (CGM), which is quite simple and convenient to calculate and use, and also has a proven connection with the development of micro- and macrovascular complications of diabetes. However, the main obstacle to the widespread use of TIR is the limited use of CGM systems. Therefore, of particular interest is the study of the derived indicator of the time in range of glycemia (derived TIR dTIR), obtained on the basis of self-monitoring of blood glucose. In this review, the issues of the relationship of TIR, dTIR with HbA1c levels, the development of micro- and macrovascular complications of diabetes type 1 and 2 are discussed, and the comparability of TIR and dTIR is analyzed.
A dangerous viral disease COVID-19, caused by a new RNA coronavirus SARS-COV-2, has been actively spreading in the world since December 2019. The main manifestations of this disease are bilateral pneumonia, often accompanied by the development of acute respiratory syndrome and respiratory failure. Patients with diabetes mellitus (DM) are at high risk of infection with the SARS-COV-2 virus, severe illness and death.Maintaining of target glycemic levels is the most important factor in a favorable outcome of COVID-19 in both type 1 and type 2 DM. The choice of antihyperglycemic therapy in a patient with DM in the acute period of COVID-19 depends on the initial therapy, the severity of hyperglycemia, the severity of the viral infection and the patient’s clinical condition.The article presents the recommendations of the board of experts of the Russian Association of Endocrinologists on glycemic control and the choice of antihyperglycemic therapy in patients with type 2 DM and COVID-19, and also on the use of glucocorticosteroids used in the treatment of COVID-19 in patients with type 2 DM.
ДИНАМИКА РАСПРОСТРАНЕННОСТИ ИШЕМИЧЕСКОЙ БОЛЕЗНИ СЕРДЦАУ ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ 2 ТИПА В ТЮМЕНСКОЙ ОБЛАСТИ ЗА 5-ЛЕТНИЙ ПЕРИОДБельчикова Л .Н . 2 , Суплотова Л
Inhibitors of the sodium-glucose cotransporter type 2 (SGLT2i) are a modern class of antihyperglycemic drugs with an insulin-independent mechanism of action. Due to its ability to effectively lower blood glucose levels, improve a number of other cardiometabolic parameters (body weight, blood pressure, uric acid), as well as reduce cardiovascular and renal risks, SGLT2i have become drugs of choice for many of patients with type 2 diabetes mellitus (T2DM). Meanwhile, along with the generally recognized classes-effects of this group of drugs, there are intragroup features, including those associated with their different selectivity in sodium-glucose cotransporters of types 1 and 2 (SGLT1 and SGLT 2). For example, one of the most studied SGLT2i, canagliflozin, in addition to its inhibitory activity against SGLT2, can also moderately block SGLT1 in the intestine and kidneys that could give a maximum efficiency in the control glycemia and others cardiometabolic parameters. In addition, canagliflozin improves not only cardiovascular, but also renal prognosis in patients with T2DM, which is reflected in the corresponding indications in the summary of product characteristics of the drug. This document summarize the established and new data regarding the efficacy and safety of canagliflozin, as well as its place in the treatment of T2DM.
Цель. Оценить частоту дефицита и недостаточности витамина D среди взрослого населения, которое проживает в регионах Российской Федерации, расположенных в широтах от 45 до 70o. Материалы и методы. Российское многоцентровое неинтервенционное регистровое исследование по методу поперечных срезов. Результаты. В проведенном исследовании 72,1% обследованных имеют статус дефицита и недостаточности витамина D, при этом адекватный уровень диагностирован в 27,8% случаях. При оценке степени недостаточности витамина D в зависимости от времени года выявлены статистически значимые различия ( p< 0,00001) между периодами: недостаточность или дефицит витамина D наблюдались у 84,2% участников весной и 62,4% – осенью. Наибольшая частота дефицита и недостаточности витамина D зафиксирована у лиц мужского пола в сравнении с женщинами ( р= 0,013, 79 и 70,3% соответственно). Дефицит витамина D наблюдался у молодых людей в возрастной подгруппе 18–25 лет ( р< 0,001, 54% в целом по исследованию) значительно чаще по сравнению с лицами более старшего возраста. Заключение. Повсеместно высокая распространенность низкой обеспеченности витамином D на территории РФ не связана с географическим регионом проживания, но в определенной степени зависит от времени года. Группу высокого риска по дефициту и недостаточности витамина D составили мужчины молодого возраста. Значительная роль витамина D в организме человека обосновывает необходимость дополнения и уточнения единой концепции по профилактике, диагностике и лечению состояний, связанных с дефицитом, что подчеркивает актуальность внедрения полученных данных в Национальные клинические рекомендации.
The presence of continuous glucose monitoring (CGM) systems has expanded diagnostic capabilities. The implementation of this technology into clinical practice allowed to determine the patterns and tendencies of excursions in glucose levels, to obtain reliable data concerning short-term glycemic control. Taking into consideration the large amount of obtained information using CGM systems, more than 30 different indicators characterizing glycemic variability were proposed. However, it is very difficult for a practitioner to interpret the data obtained due to the variety of indicators and the lack of their target values. The first step in the standardization of indices was the creation of the International Guidelines for CGM in 2017, where the Time in Range (TIR) (3,9–10,0 mmol/l, less often 3,9–7,8 mmol/l) was significant. To complement the agreed parameters and simplify the interpretation of obtained data using CGM, in 2019 the recommendations were prepared for the International Consensus on Time in Range, where TIR was validated as an additional component of the assessment of glycemic control along with HbA 1c . In the literature review the issues of the association of TIR with the development of micro- and macrovascular complications in type 1 and 2 diabetes are considered. The relationship with other indicators of the glycemic control assessment was also analyzed and the dependence of insulin therapy on TIR was shown. TIR is a simple and convenient indicator, it has a proven link with micro- and macrovascular complications of diabetes and can be recommended as a new tool for assessing the glycemic control. The main disadvantage of TIR usage is the insufficient apply of CGM technology by the majority of patients with diabetes.
IV (XXVII) Национальный конгресс эндокринологов с международным участием
Clinical guidelines have long been one of the working tools of the modern doctor, helping him quickly navigate the most effective proven methods of treatment and prevention of various diseases, and also to adapt these methods to the specific tasks of their patients and to achieve maximum personalization of treatment. Clinical practice guidelines are drawn up by professional non-profit associations and are approved by the Scientific Council of the Ministry of Health of the Russian Federation, while often one recommendation is prepared by two or even three associations. The peculiarity of the recommendations offered to your attention is that not only endocrinologists, but also therapists, cardiologists, gynecologists, gastroenterologists, and experts of many other specialties are involved in the prevention and treatment of obesity. The Multidisciplinary Working Group presents this a project in a multidisciplinary journal to bring together the efforts of several professional associations that associated with the need to pay attention not only to obesity itself but also to comorbid conditions. We are looking forward to constructive criticism and a comprehensive discussion of the problem on the pages of our journal.
AIM To assess the incidence of vitamin D deficiency and insufficiency among the adult population living in the regions of the Russian Federation located at latitudes from 45 to 70. MATERIALS AND METHODS Russian multicenter non-interventional registry study using the "cross-sectional" method. RESULTS In this study, 72.1% of the examined have the status of vitamin D deficiency and insufficiency, while an adequate level was diagnosed in 27.8% of cases. When assessing the degree of vitamin D deficiency depending on the season, statistically significant differences (p0.00001) were found between the periods: vitamin D deficiency or insufficiency was observed in 84.2% of autumn and in 62.4% of spring. The highest incidence of vitamin D deficiency and insufficiency was recorded in males compared with females (p=0.013, 79 and 70.3% respectively). Vitamin D deficiency is observed in young people in the age subgroup of 1825 years (p0.001, 54% in the study as a whole) much more often than in older people Conclusion. The widespread high prevalence of vitamin D deficiency in the Russian Federation is not related to geographic region of residence, but to some extent depends on the season. The high-risk group for vitamin D deficiency and insufficiency is young men. The significant role of vitamin D in the human body justifies the need to supplement and clarify a single concept for the prevention, diagnosis and treatment of conditions associated with deficiency, so higher implementation of National Clinical Guidelines is needed.
Oral semaglutide is the first-in-class glucagon-like peptide-1 receptor agonist available in the form of pills administered per os. PIONEER — the clinical trial program assessing the efficacy and safety of oral semaglutide — demonstrated the dose-dependent efficacy of the drug: the reduction of up to -1,4% in terms of glucose-lowering effects and the decrease of up to 5 kg in terms of weight loss. Moreover, oral semaglutide is superior in this regard compared to empagliflozin 25 mg, liraglutide 1,8 mg and sitagliptin 100 mg according to the dedicated trials of clinical program. From the cardiovascular perspective oral semaglutide has been proven to be safe. Therapeutic concentration of semaglutide in oral form is reached under several conditions: taking tablets on a daily basis in a fasting state with up to half a glass of water and waiting 30 minutes before drinking, eating, or taking other drugs. Most frequent adverse events were GLP-1 associated gastrointestinal reactions (nausea, vomiting and diarrhea), most of the events were transient and occurred generally during dose escalation.
Public organization “Russian Association of Endocrinologists”. Clinical guidlines.
Public organization “Russian Association of Endocrinologists”. Clinical guidelines.