DECLARE-TIMI 58 trial in the context of EMPA-REG OUTCOME and CANVAS

The article discussed results of the DECLARE-TIMI 58 study in the aspects of the previously finished trials (EMPA-REG OUTCOME and CANVAS). All three SGLT2i demonstrated the reduction of the risk of hospitalization for heart failure, as well as the risk of progression chronic kidney disease. At the same time, the patient populations are different. In EMPA-REG OUTCOME almost all the patients had previously diagnosed cardiovascular disease; in CANVAS 44.4% of patients did not have a confirmed cardiovascular disease, but had cardiovascular risk factors, and in DECLARE TIMI 58 there were 59% of such patients. Assessment of the published data suggests that the risk of a combined cardiovascular endpoint, including death from cardiovascular causes, myocardial infarction, and stroke, seems to be most pronounced in patients who already have established cardiovascular disease, and this effect is achieved mainly by reducing cardiovascular mortality. In the population of patients with type 2 diabetes who do not have cardiovascular disease, but who have cardiovascular risk factors, this effect is not detected. Contrary, risk-reduction of hospitalization for CHF and slowing the progression of CKD is manifested both in a population of patients with established cardiovascular disease and in the population of patients with multiple cardiovascular risk factors. In this regard, DECLARE-TIMI 58, as well as previously published data, open up new option for an earlier start of SGLT-2i for primary prevention and/or slowing the progression of nephropathy, reducing the risk of heart failure, and its prevention, as well as reduction of cardiovascular morbidity and mortality in patients with type 2 diabetes, regardless of the presence or absence of cardiovascular pathology in the anamnesis

Evaluating the Influence of Musical and Monetary Rewards on Decision Making through Computational Modelling

A central question in behavioural neuroscience is how different rewards modulate learning. While the role of monetary rewards is well-studied in decision-making research, the influence of abstract rewards like music remains poorly understood. This study investigated the dissociable effects of these two reward types on decision making. Forty participants completed two decision-making tasks, each characterised by probabilistic associations between stimuli and rewards, with probabilities changing over time to reflect environmental volatility. In each task, choices were reinforced either by monetary outcomes (win/lose) or by the endings of musical melodies (consonant/dissonant). We applied the Hierarchical Gaussian Filter, a validated hierarchical Bayesian framework, to model learning under these two conditions. Bayesian statistics provided evidence for similar learning patterns across both reward types, suggesting individuals’ similar adaptability. However, within the musical task, individual preferences for consonance over dissonance explained some aspects of learning. Specifically, correlation analyses indicated that participants more tolerant of dissonance behaved more stochastically in their belief-to-response mappings and were less likely to choose the response associated with the current prediction for a consonant ending, driven by higher volatility estimates. By contrast, participants averse to dissonance showed increased tonic volatility, leading to larger updates in reward tendency beliefs

Vascular complications of diabetes mellitus worldwide and in Russia: The path of 100 years. A review

With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic coma of the "pre-insulin era" to severe vascular complications in the modern period. The key risk factors for diabetic angiopathies in diabetes mellitus are poor glycemic control in combination with a long course of the disease. Over the past 30 years, there has been a downward trend in the incidence of late vascular complications of diabetes both worldwide and in Russia. In particular, the frequency of cardiovascular events (myocardial infarctions, strokes, amputations) decreased, and the incidence of several other complications, such as diabetic retinopathy and neuropathy, stabilized. However, the incidence of chronic kidney disease and chronic heart failure is still increasing. The Joslin Medal, awarded to patients over 50, 75 and even 80 years of life with diabetes, reflects success in the fight against this disease

Review of the results of the EASYDia international observational study. The effect of dose titration of diabeton MR on the effectiveness of treatment of type 2 diabetes

Although the number of antihyperglycemic agents has expanded significantly, sulfonylureas (in particular gliclazide MR) remain an important option in the treatment algorithms of type 2 diabetes mellitus (DM2). A large observational international study EASYDia in real clinical practice, assessing effectiveness of gliclazide MR 60 mg in patients with long-term DM2 on standard glucose-lowering therapy, showed that step-by-step intensification of therapy with gliclazide MR 60mg allows to achieve and maintain the target values of glycemia, with good tolerability even in maximum doses, low risk of hypoglycemia and no weight gain

Identifying the unmet needs of individuals with Type 2 diabetes: an international web-based survey

Aim: To identify and understand the main unmet needs of individuals with Type 2 diabetes (T2D). Materials & methods: An online survey was conducted in Brazil, China and Russia of individuals with recently diagnosed T2D. Results: The survey, involving 300 individuals with T2D, identified a need for more information regarding food/diet and for increased awareness of T2D symptoms. While most participants (94%) had experienced symptoms prior to their diagnosis, only 55% of symptomatic individuals sought medical attention. Conclusion: Novel strategies to increase awareness of diabetes should be developed and tested, and may enable earlier diagnosis and improve patients' quality of life.publishersversionpublishe

Type 2 diabetes and prediabetes prevalence in patients with different risk factor combinations in the NATION study

BACKGROUND: Type 2 diabetes (T2D) is multifactorial disease. NATION epidemiological study may provide the information about the prevalence of T2D and prediabetic state in patients with different risk factor combinations in Russian population. AIMS: To evaluate the prevalence of T2D and prediabetic state in NATION cohort depending on the amount of diabetes risk factors. MATERIALS AND METHODS: NATION is an epidemiological, cross-sectional study, designed to assess the prevalence of T2D in Russian adult population, where HbA1c was used to establish T2D (HbAc≥6,5%) and prediabetes (5,7%≤HbA1c<6,5%). Patients with T2D were either previously diagnosed or newly diagnosed. Current study presents an additional analysis of NATION cohort focused on the prevalence of T2D and prediabetic state among patients with different risk factor combinations. RESULTS: T2D and prediabetic state prevalence gradually increased among patients with following risk factors (prevalence of T2D and prediabetes respectively): low physical activity (4,3%, 18,3%), rare fruit and vegetable consumption (4,8%, 18,7%), T2D family history (7,7%, 20,3%), age ≥45 years (9,5%, 31,3%), obesity grade 1 (9,6%, 30,3%), obesity grade 2 (14,6%, 37,8%), obesity grade 3 (20,1%, 39,7%), hypertension (14,7%, 38,2%), history of diabetes during pregnancy (14,1%, 24,7%). Prevalence of T2D with single and multiple risk factors was compared to the prevalence of T2D in young patients (<45 years) without additional diabetes risk factors. Age ≥45 years was associated with 7-fold increase in T2D prevalence; obesity – 8,8-fold; family history – 5,7-fold; hypertension – 10,8-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors). When one patient had several risk factors combined, the prevalence of T2D increased progressively: combination of age ≥45 years and family history led to 10,7-fold rise; combination of age ≥45 years and BMI≥30kg/m2 – 11,2-fold; combination of age ≥45 years, family history and BMI≥30kg/m2 – 15,3-fold; combination of age ≥45 years, family history, BMI≥30kg/m2 and hypertension – 19,1-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors). CONCLUSIONS: Presence of multiple risk factors, such as age ≥45 years, obesity and hypertension led to progressive increase in the prevalence of T2D and prediabetic state. These data are important to identify patients at the highest risk of T2D among Russian population

cover letter

Recently, the bihormonal theory of the autoimmune diabetes development is discussed in the world literature. The abnormal suppression of glucagon and reduced incretin response are considered in the development and progression of type 1 diabetes mellitus in addition to insulin deficiency. Animal studies demonstrate a GLP-1 – role in beta cell-proliferation and decrease in apoptosis. The information concerning the functioning of the incretin system in patients with type 1 diabetes and LADA is systematized in the present review. We also discuss the studies of the use of GLP-1 agonists in patients with autoimmune diabetes

The effect of bariatric surgery on purine metabolism and gout

Gout is an auto-inflammatory tophaceous disease characterized by the deposition of crystals of monosodium urate and developing in connection with this inflammation in people with hyperuricemia (HU). Except to genetic factors, risk factors for the development of HU and gout are many modifiable factors, including metabolic syndrome and obesity, and their correction is the most important component of successful disease control. Obesity can change the clinical picture of gout, characterized by an earlier onset, a large number of affected joints. Weight loss helps reduce uric acid (UA) serum levels. Bariatric / metabolic surgery significantly reduces the incidence of comorbid obesity and mortality, and is by far the most effective way to combat obesity. In addition to improving health, an important goal of bariatric surgery is to improve the quality of life. Bariatric surgery can prevent the development of HU in subjects with an initially normal level of serum UA before surgery. The dynamics of the concentration of UA in serum can be a predictor of successful bariatric surgery and help in predicting the severity of postoperative weight loss. The decrease in body weight after bariatric surgery leads to a decrease in UA in the long-term postoperative period, however, there is a high frequency of acute gout attacks in the early postoperative period. Thus, bariatric surgery has a significant effect on HU and gout and can be an effective treatment for this disease

Rational approach to patients treatment with type 2 diabetes and obesity: results of the All-Russian observational program «AURORA»

Background: As in many other developed nations, the problem of obesity and type 2 diabetes is acute in Russia. In Russia, the only combination of sibutramine and metformine (Reduxin®Met) is authorized to reduce body mass and prevention development of type 2 diabetes mellitus or its complication. The article presents the results of the observational program “AVRORA”. Aim: Evaluation of the effectiveness and safety of Reduxin®Met (sibutramine + microcrystalline cellulose + Metformin) in patients with type 2 diabetes and alimentary obesity in routine clinical practice. Materials & methods: The observational program “AVRORA” was conducted from September 2016 to October 2017 under the auspices of the Endocrinological Scientific Center and the Russian Association of Endocrinologists. The “AVRORA” program was a multicenter, non-interventional study of patients to whom the attending physicians prescribed Reduxin®Met, a set (tablets + capsules), in accordance with the instruction for medical use as part of routine clinical practice. The treated group included patients of both sexes, aged 18–65 years, with an established diagnosis of obesity in combination with type 2 diabetes. The duration of the drug usage was determined by the attending physician and was up to 6 months. Reduxine®Met was prescribed in addition to the existing glucose-lowering therapy, the dose of metformin was adjusted to the patient's needs. Results: The “AVRORA” study was attended by 259 doctors and 5,812 patients in 240 medical institutions from 12 cities of the Russian Federation. The average age of patients was 46.6 ± 10.5 years, the ratio of male / female -24% / 76%. The decreasing of BMI during 6 months of the therapy amounted to 5.4 ± 2.3 kg / m2 (on average, 15.1 ± 6.4 kg). After 3 months of the therapy 81.6% of patients achieved clinically significant weight loss of 10.6% or more. The average decrease in waist circumference during 6 months of therapy was 13.8 ± 7.4 cm. A decrease of indicators of glycemic control and lipid metabolism right up to the target values was observed. Conclusions: In “AVRORA” study it was shown that addition of Reduxine®Met (sibutramine+ microcrystalline cellulose+metformine) to the complex therapy of the diabetes in combination with obesity according to approved indications is safe and effective for long-term treatment in regards to weight loss, regulation of lipemic index, glucose profile and quality of life

Nephroprotective potential of glucagon-like peptide-1 receptor agonists

Patients with diabetes mellitus (DM), which is a key factor in the development of kidney diseases, are increasingly competing for limited healthcare resources. Diabetic kidney disease (DKD) remains a significant cause of end-stage renal failure in the patients of many countries and is also associated with a high risk of cardiovascular pathology and mortality. The variety of clinical phenotypes of DKD in patients with type 2 diabetes mellitus (DM2) occurring due to a variety of pathogenetic factors and the characteristics of the evolution of complications under the influence of contemporary therapeutic methods, has been a special subject of discussion in recent years. Optimal control of the level of glycaemia and hypertension and timely blockade of the renin–angiotensin–aldosterone system do not provide sufficient protection for the kidneys. Over the recent decade, the nephroprotective potential of a group of modern anti-hyperglycaemic agents, i.e., glucagon-like peptide 1 receptor agonists (GLP1 RA) has been actively discussed. GLP1 RA have proven to be quite effective in controlling glycaemia and metabolic syndrome components (weight, systolic blood pressure and lipid profile) and in significantly reducing the risk of the primary, three-component endpoint (major adverse cardiac events: cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) according to large studies on cardiovascular safety. The renal effects of GLP1 RA are attributed to a wide range of direct and indirect effects of glucagon-like peptide-1 on renal structures and functions owing to their anti-inflammatory, anti-oxidant and anti-apoptotic properties