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

Diabetes mellitus type 2 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.&nbsp

Diabetes mellitus type 1 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidlines

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 10th edition

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 Grou

Obesity and type 2 diabetes: can we find a compromised treatment solution?

Type 2 diabetes and obesity are two enormous epidemic diseases of the 21stcentury. Because obesity is a primary risk factor for type 2 diabetes development, patients with diabetes are frequently obese. This comorbidity makes it challenging for these patients to not only compensate diabetes but also bring their weight back to normal. Several anti-diabetic drugs cause weight gain, which augments insulin resistance, and thus demands anti-diabetic treatment intensification. For the treatment, it is crucial to find an anti-diabetic treatment drug that is efficient but does not cause weight gain. In the last few decades, new anti-diabetic drugs with minimal or decrementing effects on the body weight have been introduced. New molecules appearing in the anti-obesity treatment are capable of not only reducing weight but also compensating diabetes. This study focuses on the current anti-obesity and anti-diabetic treatment and optimal combinations for treating comorbid patients

Correction of mineral and bone disorders in a patient with long-standing diabetes mellitus type 1 on hemodialysis therapy

Osteoporosis and diabetes mellitus (DM) – chronic diseases with constantly growing prevalence. Patients with DM have the increased risk of bones fractures. Risk of fracture in the patient with diabetes mellitus type 1 (DM1) is increased by more than 6 times. There are several mechanisms leading to the development of osteoporosis in DM: chronic hyperglycemia, insulin deficiency, genetic factors, and complications of DM. Moreover, the chronic kidney disease in DM impacts not only progression of osteoporosis, but also leads to emergence of other bone disorders, that considerably complicate a choice of antiosteoporotic treatment. This article describes a clinical case of the mineral and bone disorders of a phosphorus-calcium metabolism, which developed in patient with long history of DM1 receiving therapy by a program hemodialysis

Correction of mineral and bone disorders in a patient with long-standing diabetes mellitus type 1 on hemodialysis therapy

Osteoporosis and diabetes mellitus (DM) – chronic diseases with constantly growing prevalence. Patients with DM have the increased risk of bones fractures. Risk of fracture in the patient with diabetes mellitus type 1 (DM1) is increased by more than 6 times. There are several mechanisms leading to the development of osteoporosis in DM: chronic hyperglycemia, insulin deficiency, genetic factors, and complications of DM. Moreover, the chronic kidney disease in DM impacts not only progression of osteoporosis, but also leads to emergence of other bone disorders, that considerably complicate a choice of antiosteoporotic treatment. This article describes a clinical case of the mineral and bone disorders of a phosphorus-calcium metabolism, which developed in patient with long history of DM1 receiving therapy by a program hemodialysis

Comparative analysis of glycemic control effectiveness and microvascular complications in patients with type 1 diabetes mellitus, treated with genetically engineered human insulin or human insulin analogues: A 10-year retrospective observational study

The treatment of diabetes mellitus generally involves genetically engineered human insulin (GICH) or genetically engineered analogues of human insulin (AIC). Compared to GICH, AIC better physiologically mimics endogenous insulin functionally. It would thus be logical to assume that long-term (multi-year) application of AIC leads to a lower incidence of diabetic angiopathy compared to GICH. To date, however, no long-term comparisons of both classes of insulin preparations (in terms of efficacy of glycemic control or incidence of microvascular complications in patients with type 1 diabetes) have been performed. Aims. To retrospectively compare the efficacy of glycemic control and incidence of microvascular complications (nephropathy and retinopathy) in patients with type 1 diabetes treated for at least 10 years with either GICH or AIC. Materials and methods. Based on data from electronic databases (diabetes registry) from several regions within the Russian Federation, the following patient samples were examined (n=260): group 1 received GICH for 10 years (n = 130) and group 2 received AIC for 10 years (n = 130). Patients in both groups underwent pairwise matching for baseline clinical characteristics (sex, age of diabetes onset, duration of disease and HbA1clevel). All patients were observed by endocrinologists in the clinic. Results. After 10 years of follow up, HbA1с levels declined more significantly in group 2 than in group 1 (1.30% vs. 0.81%, respectively, P 0.05). By the end of the observation period, the presence of diabetic retinopathy (any stage) increased in both groups and was not significantly different between groups; the presence of diabetic nephropathy was also increased in both groups, but the increase was significantly lower in group 2 than in group 1 (20.5% vs. 33.9%, respectively, P 0.05). Overall, the risk of microvascular complications was significantly higher in group 1 than in group 2 [HR (hazard ratio): 1.84; 95% CI: 1.372.48), specifically, the risk of diabetic retinopathy (HR: 1.37; 95% CI: 0.981.90). Conclusions. A 10-year retrospective analysis of patients treated with AIC for type 1 diabetes in the clinic showed a significantly more effective reduction in HbA1c levels and a lower incidence of diabetic nephropathy, compared with patients treated with GICH

Shear Stress and the AMP-Activated Protein Kinase Independently Protect the Vascular Endothelium from Palmitate Lipotoxicity

Saturated free fatty acids are thought to play a critical role in metabolic disorders associated with obesity, insulin resistance, type 2 diabetes (T2D), and their vascular complications via effects on the vascular endothelium. The most abundant saturated free fatty acid, palmitate, exerts lipotoxic effects on the vascular endothelium, eventually leading to cell death. Shear stress activates the endothelial AMP-activated protein kinase (AMPK), a cellular energy sensor, and protects endothelial cells from lipotoxicity, however their relationship is uncertain. Here, we used isoform-specific shRNA-mediated silencing of AMPK to explore its involvement in the long-term protection of macrovascular human umbilical vein endothelial cells (HUVECs) against palmitate lipotoxicity and to relate it to the effects of shear stress. We demonstrated that it is the α1 catalytic subunit of AMPK that is critical for HUVEC protection under static conditions, whereas AMPK-α2 autocompensated a substantial loss of AMPK-α1, but failed to protect the cells from palmitate. Shear stress equally protected the wild type HUVECs and those lacking either α1, or α2, or both AMPK-α isoforms; however, the protective effect of AMPK reappeared after returning to static conditions. Moreover, in human adipose microvascular endothelial cells isolated from obese diabetic individuals, shear stress was a strong protector from palmitate lipotoxicity, thus highlighting the importance of circulation that is often obstructed in obesity/T2D. Altogether, these results indicate that AMPK is important for vascular endothelial cell protection against lipotoxicity in the static environment, however it may be dispensable for persistent and more effective protection exerted by shear stress