34 research outputs found
Current data on the effectiveness of gliclazide and molecular mechanisms of action of the drug
With the growing prevalence of type 2 diabetes mellitus (T2DM) the possibility of treating it with available drugs is one of the main issues. Although glycemic control and reduction of micro- and macrovascular outcomes remain important aspects of treatment, the main limiting factors are the availability and cost of oral hypoglycemic agents. Although newer agents, such as sodium -glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists, potentially being valuable for patients with insulin resistance and cardiovascular complications, they are relatively expensive and have limited availability. Second-generation sulfonylureas effectively reduce glycated hemoglobin and contribute to the prevention of micro- and macrovascular complications of T2DM The review substantiates the role of Gliclazide MR as a more affordable drug for the treatment of T2DM, the safety of which has been confirmed by many studies; cardio-and nephroprotective effects are shown, as well as mechanisms for influencing Π²-cells of the pancreas and extrapancreatic effects through activation of phospholipase C and the G-protein-Ρoupled-receptors (GPCR) are analyzed. The latest data on the assessment of adverse events of Gliclazide MR are presented in comparison with both other sulfonylureas and glucose-lowering drugs of other classes
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
Heart failure and diabetes mellitus: insight into comorbidity
Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities with a bidirectional relationship. Patients with HF have increased risk of developing DM, and those with DM are at greater risk of developing HF. HF does not fit clearly into the microangiopathy and macroangiopathy groups. It is known that coronary artery disease and arterial hypertension are the major causes of HF; however, it has been shown that DM can trigger functional and structural abnormalities in the myocardium via diabetic cardiomyopathy, a condition with either restrictive or dilated phenotype. While HF treatment is equally effective and safe in patients with and without DM, this statement is not applicable for antidiabetic treatment. Several antidiabetic drugs, such as rosiglitazone, pioglitazone and saxagliptin increase the risk of hospitalisation for HF, therefore these antidiabetic drugs are contraindicated in patients with DM and HF or patients at risk of developing HF. Despite a large number of clinical evidence, uncertainty about the safety of antidiabetic drugs in patients with HF always exists. In this review, the issues of DM treatment in patients with HF are addressed in detail
Π‘ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠ΅ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΈ ΠΈΠ½Π²ΠΎΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΠΊΠΎΠΆΠΈ ΠΈ ΠΌΠ΅ΡΡΠΎ ΡΠΎΡΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΡΠ΅Π΄ΠΈ Π½ΠΈΡ
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.ΠΠ°Π½Π½Π°Ρ ΡΠ°Π±ΠΎΡΠ° ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΎΠ±ΠΎΠΉ ΠΎΠ±Π·ΠΎΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
Π½Π°ΡΡΠ½ΡΡ
Π΄Π°Π½Π½ΡΡ
ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ°Ρ
ΡΡΠ°ΡΠ΅Π½ΠΈΡ ΠΊΠΎΠΆΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΎ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π΅ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄Π° ΡΠΎΡΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π΄Π»Ρ ΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΈ ΠΈΠ½Π²ΠΎΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΠΊΠΎΠΆΠΈ Ρ Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΠΎΠ³ΠΎ Π½Π°ΡΠ΅Π»Π΅Π½ΠΈΡ. ΠΡΠΈΠ²ΠΎΠ΄ΡΡΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΡΠ΅ΠΌΠΎΠ³ΠΎ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΆΠΈΠ·Π½ΠΈ ΠΈ, ΠΊΠ°ΠΊ ΡΠ»Π΅Π΄ΡΡΠ²ΠΈΠ΅, ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΈΡΠΊΠ° Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΊΠΎΠΆΠ½ΠΎΠΉ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ. Π£Π²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΆΠΈΠ·Π½ΠΈ ΡΠ°ΠΊΠΆΠ΅ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΠ΅Ρ ΠΈ ΡΠΎΡΠΈΠ°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΏΠΎΠΆΠΈΠ»ΠΎΠ³ΠΎ Π½Π°ΡΠ΅Π»Π΅Π½ΠΈΡ, Π²ΠΌΠ΅ΡΡΠ΅ Ρ ΡΠ΅ΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ°ΡΡΡΡ ΠΏΠΎΡΡΠ΅Π±Π½ΠΎΡΡΡ Π² ΠΏΡΠ΅ΠΎΠ±ΡΠ°ΠΆΠ΅Π½ΠΈΠΈ ΠΈ ΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΈ ΠΈΠ½Π²ΠΎΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΠΊΠΎΠΆΠΈ, Π½ΠΎ, ΡΡΠΈΡΡΠ²Π°Ρ ΡΠΈΡΠΊΠΈ Π² ΡΠ²ΡΠ·ΠΈ Ρ Π½Π°Π»ΠΈΡΠΈΠ΅ΠΌ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΈ Π²ΠΎΠ·ΡΠ°ΡΡΠ°ΡΡΠ΅ΠΉ ΠΌΠ°Π»ΠΈΠ³Π½ΠΈΠ·Π°ΡΠΈΠΈ Π΄Π°Π½Π½ΠΎΠΉ ΠΊΠΎΠ³ΠΎΡΡΡ, ΡΠ»Π΅Π΄ΡΠ΅Ρ ΡΡΠ°ΡΠ΅Π»ΡΠ½ΠΎ ΠΏΠΎΠ΄Π±ΠΈΡΠ°ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ, ΡΡΠΈΡΡΠ²Π°Ρ Π²ΡΡΠ΅ΠΏΠ΅ΡΠ΅ΡΠΈΡΠ»Π΅Π½Π½ΡΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ. ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· ΡΠ°ΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠΎΡΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ. Π€ΠΎΡΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΡΡΡ Π² ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ, Π° Π² ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ Π²ΡΠ΅ ΡΠ°ΡΠ΅ ΠΏΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ ΡΠ²ΠΎΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π² ΡΡΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠΈ, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΡΠ΅ΠΌΠΎ ΠΌΠΎΠΆΠ΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡΡΡ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π±ΠΎΠ»ΡΠ½ΡΡ
, Π½ΠΎ ΠΈ Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΠΎΠΉ ΠΊΠΎΠ³ΠΎΡΡΡ
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
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
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 Ξ²-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.Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΡΠ°ΡΡΠ΅ ΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π‘Π°Ρ
Π°ΡΠ½ΡΠΌ Π΄ΠΈΠ°Π±Π΅ΡΠΎΠΌ 1 ΡΠΈΠΏΠ° Π½Π°Ρ
ΠΎΠ΄ΡΡΠΈΡ
ΡΡ Π² ΡΠ½Π΄ΠΎΠΊΡΠΈΠ½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠ»ΠΈΠ½ΠΈΠΊΠ°Ρ
. Π Ρ
ΠΎΠ΄Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠΈΡΡΠ²Π°Π»ΠΈΡΡ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΡΠΎΠΏΡΡΡΡΠ²ΡΡΡΠΈΠ΅ Π°ΡΡΠΎΠΈΠΌΠΌΡΠ½Π½ΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ, Π½Π°Π»ΠΈΡΠΈΠ΅ Π΄ΠΈΠ°Π±Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π½Π΅ΡΡΠΎ- ΠΈ ΡΠ΅ΡΠΈΠ½ΠΎΠΏΠ°ΡΠΈΠΉ, Π°Π½Π³ΠΈΠΎΠΏΠ°ΡΠΈΠΈ, ΠΎΡΡΠ΅ΠΎΠ°ΡΡΡΠΎΠΏΠ°ΡΠΈΠΉ
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.Β SGLT2i show less glycemic efficacy in comparison with GLP-1 RA, and their replacement may need adding antidiabetic agents from other groups
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