[Finerenone cardiorenal effects and its placement in treatment of chronic kidney disease in patients with type 2 diabetes mellitus: A review].

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high. To date, current medications for CKD haven't reduced enough the residual risk associated with inflammation and fibrosis in patients with type 2 diabetes. Here, in this review we present the results of FIDELIO-DKD, FIGARO-DKD trials and their pooled analysis FIDELITY, aimed to evaluate the effectiveness and safety of selective non-steroidal mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes with wide range stages of CKD. Modern pathophysiological aspects of mineralocorticoid receptor hyperactivation and features of their blockade by steroidal and nonsteroidal mineralocorticoid receptor antagonists are considered, differences in pharmacological effects between them are also discussed, finerenone benefits and its adverse events, demonstrated in randomized clinical trials are considered here. The probable mechanisms of early and delayed action of finerenone, which were realized in beneficial cardiovascular and renal outcomes in patients with type 2 diabetes with CKD, are presented here. Practical points for finerenone initiation and titration are indicated, aimed to minimize the hyperkalemia risk. Current guidelines for CKD treatment in patients with type 2 diabetes are analyzed, the finerenone placement in combined nephroprotective therapy is determined.

[Sub-analyses of the DAPA-CKD study: new data on the use of sodium-glucose cotransporter type 2 inhibitor in the treatment of chronic kidney disease].

Sodium-glucose cotransporter inhibitors updated their position in the therapy of patients with type 2 diabetes mellitus due to proven nephro- and cardioprotective effects. The DAPA-CKD study, performed among individuals with CKD of various etiologies, was also conducted in a mixed population, including patients without type 2 diabetes, showed the ability of dapagliflozin to reduce the risk of the primary combined endpoint (eGFR<15 ml/min/1.73 m2, the need for chronic dialysis or kidney transplantation, time to renal or cardiovascular death), and certain secondary endpoints. Due to the inclusion of dapagliflozin into the treatment of the patients with CKD of not only the diabetic origin and the expected subsequent significant expansion of the patient population with indications for the use of this drug, the review of the results of the sub-analyses of DAPA-CKD study may be of interest to the clinicians.

[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

[Glycemic control in patients with diabetes mellitus on hemodialysis].

Achievement of stabilization of carbohydrate metabolism in patients with diabetes mellitus, receiving renal replacement therapy with hemodialysis, is a significant problem in endocrinology. It has to do with multiple factors of this cohort of patients, which affect the level of glycemia, pharmacokinetic of drugs, the efficiency of glycemic control. At the moment, the most efficiency method of glycemic control in patients with type 2 diabetes mellitus on hemodialysis is insulin therapy in the basis - bolus regime by analogues of human insulin. The use of oral hypoglycemic agents is significantly limited. The hemoglobin A1c (HbA1c) remains the main parameter of glycemic control. The simultaneous use of continuous glucose monitoring allows to reveal the true level of glucose of the blood and to carry out the timely correction of therapy in order to achieve targets for glycemic control and to decrease the risk of hypoglycemic episodes. At the moment other glycemic control markers such as glycated albumin and fructosamine are described. However, in routine practice at the moment these indicators are not used due to the lack of sufficient evidentiary base of their use in this cohort of patients.

Renal experiences of bariatric surgery in patients with type 2 diabetes mellitus.

The review addresses the questions of the literature devoted to the problem of the influence of bariatric surgery on the course of diabetic nephropathy in patients with diabetes mellitus type 2 after achieving a surgically induced remission. This approach was shown to have positive aspects, such as decrease in creatinine, decrease in albuminuria, an increase in GFR, normalization of glycemia and blood pressure, "incretin effect"'s influence on the kidneys. Descriptions of the currently expected pathogenetic mechanisms involved in achieving the observed improvement in microvascular complications of diabetes, namely diabetic kidney disease, are also described in details.

Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes.

The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A+A/G (P=0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. A HOMA-beta value characterizing the beta-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0+/-46.9) then for other genotypes (HOMA-beta = 85.6+/-45.5 for A/A+A/G, P=0.0015). The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.

[Apidra is a new insulin analogue for the treatment of vascular complications in diabetes].

To achieve glycemic targets, as the main preventive measure for vascular complications, patients with type 1 diabetes need lifelong administration of insulin in a regimen that allows them to have euglycemia both before and after eating. For this, optimal insulin therapy regimens have been created, which necessarily include short-acting insulin (with the main meal) and medium or long-acting insulin as basal. This mode of administration allows you to maximize bring the daily fluctuations of insulin administered to the natural rhythm of insulin secretion in healthy people.

[The polymorphic markers of АРОВ and APOE genes and the chromosomal region 3q21-q25 are associated with the development of diabetic nephropathy in type 1 diabetes mellitus].

Early studies of the association of a large group of gene candidates indicated that only the polymorphic markers of angiotensin-converting enzyme (ACE) I gene and endothelial vascular cell NO-synthetase (NOS3) gene were associated with diabetic nephropathy (DN) in type 1 diabetes mellitus. The purpose of this study was to examine DN predisposition in patients with type 1 DM, by using the polymorphic markers of the genes of apolipoproteins Е (АРОЕ) and В (АРОВ) which encode for lipid metabolic proteins, as well as polymorphic microsatellites in the chromosomal region 3q21-q25. Two groups of patients of patients with type 1 DM with (n = 54) and without (n = 65) DN were examined to analyze the gene association with DN. Analyzing the frequencies of the alleles and genotypes of the polymorphic marker E2/E3/E4 ofAPOR gene has indicated that the carriers of the allele E3 and the genotype E3/ E3 have a higher risk for DN (OR = 2.08 and 2.16, respectively). In case of АРОВ gene, the carriers of allele I and genotype II of the polymorphic marker I/D have been ascertained to have a higher risk for DN (OR = 1.91 and 2.11, respectively) while those of allele Dhave, on the contrary, a lower risk for DN (OR = 0.52). The authors have revealed an association of a group of polymorphic microsatellites with DN in the chromosomal region 3q21-q25. There is the greatest association for the marker D31550. The carriers of allele 12 (OR = 4.85) and genotype 12/14 (OR = 6.25) have a much higher risk for DN. In all probability, in the chromosomal region 3q21-q25, there is a major gene that initiates the development of DN whereas other genes associated with DN affect the rate of its progression to a greater extent. Thus, among the Moscow Russian dwellers suffering from type 1 DM, the progression of DN is mainly associated with the genes of ACE, NOS3, APOE, and АРОВ while the major gene that determines the first stages of DN development in type 1 DM is likely to be located in the chromosomal region 3q21-q25.