Some mechanisms of inflammation development in type 2 diabetes mellitus

Inflammation plays a key role in the development and progression of type 2 diabetes (T2DM), a disease characterized by peripheral insulin resistance and systemic glucolipotoxicity. The main source of inflammation in the early stages of the disease is visceral adipose tissue (VT). Macrophages are innate immune cells that are present in all peripheral tissues, including VT. Violation of the response of VT (MT) macrophages to changes in the microenvironment underlies aberrant inflammation and the development of local and systemic insulin resistance. The inflammatory activation of macrophages is regulated at several levels: stimulation of cell surface receptors, intracellular signaling, transcription, and metabolic levels. Which are activated by the transformation of macrophages along the pro-inflammatory or anti-inflammatory pathways. Such polarization of macrophages in modern immunology is divided into classical anti-inflammatory M1 polarization and alternative anti-inflammatory M2 polarization of macrophages. The M1 / M2 ratio of macrophages in the process of inflammation ensures the resolution of inflammation at different stages of its development. The review considers the main mechanisms involved in VT inflammation and the development of insulin resistance in T2DM, supported with the participation of immunocompetent cells, M1 / M2, as well as growth factors and humoral immunity factors secreted during this process

Современное состояние методов коррекции инволюционных изменений кожи и место фотодинамической терапии среди них

This work is a review of modern scientific data on the process of aging, as well as the prospect of using photodynamic therapy for correction of involutional skin changes in the age cohorts, cohorts with a burdened medical history, including cancerous and precancerous skin neoplasms. The data on the predicted increase in life expectancy and, as a consequence, the potential risk of pathologies, including those with skin localization, progression of malignancy processes, as well as the formation of de novo elements, is presented. The increase in life expectancy also demonstrates the socialization of the elderly population, along with the increasing need for correction of involutional skin changes. However, considering the risks associated with the chronic diseases and increased malignancy in this cohort, methods have to be carefully selected. One such technique is photodynamic therapy (PDT). PDT is actively used in oncology, and recently has been increasingly showing its aesthetic effectiveness. It can be predictably used not only on cancer patients, but also in an age cohort.Данная работа представляет собой обзор современных научных данных о процессах старения кожи, а также о перспективе использования метода фотодинамической терапии для коррекции инволюционных изменений кожи у возрастного населения. Приводятся данные прогнозируемого увеличения продолжительности жизни и, как следствие, потенциального риска возникновения патологий, в том числе кожной локализации. Увеличение продолжительности жизни также демонстрирует и социализацию пожилого населения, вместе с тем возрастающую потребность в преображении и коррекции инволюционных изменений кожи, но, учитывая риски в связи с наличием хронических заболеваний и возрастающей малигнизации данной когорты, следует тщательно подбирать методики, учитывая вышеперечисленные особенности. Одним из таких методов является фотодинамическая терапия. Фотодинамическая терапия активно применяется в онкологии, а в последнее время все чаще показывает свою эффективность в эстетическом направлении, соответственно прогнозируемо может использоваться не только у онкологических больных, но и возрастной когорты

The role of pioglitazone in the fight against insulin resistance, atherosclerosis, cardiovascular disease, and non-alcoholic fatty liver disease

Modern strategies for the treatment of type 2 diabetes mellitus involve the use of pathogenetically based approaches aimed at achieving optimal glycemic control and its long-term retention. Timely and rational use of 9 classes of hypoglycemic drugs, including as part of combination therapy, makes it possible to achieve significant success in diabetes therapy. One of the fundamental principles in the treatment of type 2 diabetes mellitus is the effect on insulin resistance. For this purpose, two groups of drugs are used: biguanides and thiazolidinediones (glitazones). The action of glitazones is directly related to an increase in the sensitivity of insulin-dependent tissues to insulin and a pronounced decrease in hyperinsulinemia in patients with type 2 diabetes. Of particular interest are the pathways of insulin signal transduction, the mechanisms of insulin resistance, and the possibilities of pathogenetic therapy with thiazolidinediones. Pioglitazone is currently the only available member of the thiazolidinedione class in the world, allowing to expand the management of diabetes mellitus by reducing insulin resistance in muscle and adipose tissue and glucose production by the liver. Its use can have a number of pleiotropic effects, including on cardiovascular diseases and non-alcoholic fatty liver disease, which expands the priorities for choosing hypoglycemic therapy in patients with type 2 diabetes at various stages of therapy

Possibilities of application a fixed combination of alogliptin and pioglitazone for type 2 diabetes mellitus treatment

Hyperglycemia in T2DM is based on three main mechanisms: insulin resistance, progressive β-cell dysfunction, and excess glucose production by the liver.The onset of T2DM is usually preceded by a long period of insulin resistance. Prescribing sugar drugs that affect different links of pathogenesis, reducing a steady decrease in glycemia. To date, in clinical practice, various combinations of hypoglycemic drugs are used, the choice of which is determined by the characteristics of the course of diabetes in the patient, the presence of concomitant diseases and complications of diabetes, as well as the dominant clinical problem. This resolution provides an expert council opinion on the feasibility of using a combination of alogliptin and pioglitazone in patients with type 2 diabetes

Analysis of the causes of hospitalization and screening of complications in patients with type 1 diabetes in the endocrinological hospital.

This article made a study of patients with type 1 diabetes who are in endocrinological clinics. In the course of the study, concomitant autoimmune diseases, the presence of diabetic nephropathy and retinopathy, angiopathy, and osteoarthropathy were taken into account in patients.В настоящей статье произведено исследование пациентов с Сахарным диабетом 1 типа находящихся в эндокринологических клиниках. В ходе исследование учитывались у пациентов сопутствующие аутоиммунные заболевания, наличие диабетических нефро- и ретинопатий, ангиопатии, остеоартропатий

Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome

AIMS: Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS: 121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS: A correlation was found between HbA1c and levels of stimulated secretion of TNFα (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF-α and CCL18 was observed (p<0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNFα and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher. CONCLUSION: Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory

The advisory board resolution on the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes

Type 2 diabetes is characterized by increasing incidence and prevalence all-over the world. Current therapeutic management of type 2 diabetes is complex and is based not only on glycemic control, but also on cardiovascular and renal risks reduction. In previous years the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) increased in Russian Federation. Some manufacturers of the most widely used GLP-1 RA reported the supply decline in several countries. On Advisory board with participation of the Russian Endocrinology Association members the topics of SGLT2i and GLP-1 RA use in type 2 diabetes were discussed. The experts made conclusion that the decrease in access to GLP-1 RA does not pose serious risk for treatment of type 2 diabetes patients. SGLT2i show benefits in risk reduction of HF and CKD progression compering to GLP-1 RA, and in general show comparable efficacy in risk reduction of ACVD outcomes.  SGLT2i show less glycemic efficacy in comparison with GLP-1 RA, and their replacement may need adding antidiabetic agents from other groups

Management of diabetes during Ramadan: an update for Russian-speaking doctors

Fasting during the Islamic Ramadan month is one of the five obligatory pillars for each adult, healthy, and sane Muslim. People with severe illnesses, including type 1 and type 2 diabetes mellitus are exempt from fasting. However, many Muslims often insist on Ramadan participating despite any medical advises. It’s known that Muslims are the second largest religious group in Russia; thus, its crucial to have as much modern recommendation for management patients with type 1 and type 2 diabetes mellitus as possible. The aim of this narrative review is to evaluate physiological and pathophysiological metabolism changing during holy Ramadan month, to clarify the management of patients with type 1 and type 2 diabetes mellitus during Ramadan, to determine the frequency of glucose measuring during the day, and to understand when its time to interrupt the fasting. Moreover, we discuss specific recommendations in glucose-lowering therapy changing, nutrition, physical activities and education

What are new opportunities for clinical practice the VERIFY study opens and which values for native diabetes patients? Joint conclusion on the advisory board results. November 6, 2019

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications. However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target. A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients

Glycemia control and choice of antihyperglycemic therapy in patients with type 2 diabetes mellitus and COVID-19: a consensus decision of the board of experts of the Russian association of endocrinologists

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