[Diabetes mellitus type 2: National Russian guidelines vs real clinical practice].

According to the "Federal Law on the Fundamentals of Protection of the Public Health", medical care for patients should be provided in accordance with National Russian guidelines for the relevant nosology, which are based on the principles of evidence-based medicine. The article presents an analysis of the compliance with the completeness of implementation of National Russian guidelines in the treatment of patients with type 2 diabetes mellitus (DM 2) in real clinical practice. The analysis of the actual state of management of DM 2 patients was carried out from the Federal Register of diabetes as of 01.01.2023. Incomplete compliance with the guidelines on the frequency of measuring glycated hemoglobin, the rate of intensification of hypoglycemic therapy, and the appointment of new classes of hypoglycemic drugs was established. Possible reasons for the identified discrepancies between real practice and guidelines requirements are discussed, as well as possible measures to overcome these discrepancies.

[Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19].

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. AIM: The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. MATERIALS AND METHODS: The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. RESULTS: The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. CONCLUSION: In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

Risk factors for COVID-19 case fatality rate in people with type 1 and type 2 diabetes mellitus: A nationwide retrospective cohort study of 235,248 patients in the Russian Federation.

The aim: To study the association of demographic, clinical, and laboratory factors and the use of glucose-lowering drugs and anti-coronavirus disease (COVID-19) vaccination with the COVID-19-related case fatality rate (CFR) in diabetes mellitus (DM) patients. Methods: This study is a nationwide observational cohort study based on the data from the National Diabetes Register (NDR) that is the database containing online clinical information about the population with DM. The outcomes (death or recovery) for COVID-19 were registered in 235,248 patients with DM [type 1 diabetes mellitus (T1DM), n = 11,058; type 2 diabetes mellitus (T2DM), n = 224,190] from March 20, 2020, until November 25, 2021. The unadjusted odds ratio (OR) and 95% confidence interval (CI) were used to estimate the risk factors for CFR. Then the ranging of significant factors was performed and the most vulnerable groups of factors for the lethal outcome were chosen. Results: The CFR due to COVID-19 was 8.1% in T1DM and 15.3% in T2DM. Increased CFR was associated with the male population [OR = 1.25 (95% CI: 1.09-1.44) in T1DM and 1.18 (95% CI: 1.15-1.21) in T2DM], age ≥65 years [OR = 4.44 (95% CI: 3.75-5.24) in T1DM and 3.18 (95% CI: 3.09-3.26) in T2DM], DM duration ≥10 years [OR = 2.46 (95% CI: 2.06-2.95) in T1DM and 2.11 (95% CI: 2.06-2.16) in T2DM], body mass index (BMI) ≥30 kg/m2 [OR = 1.95 (95% CI: 1.52-2.50)] in T1DM, HbA1c ≥7% [OR = 1.35 (95% CI: 1.29-1.43)] in T2DM. The atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD) were associated with higher CFR in T1DM but not in T2DM. The pre-COVID-19 glucose-lowering therapy in T2DM was differently associated with CFR (OR): 0.61 (95% CI: 0.59-0.62) for metformin, 0.59 (95% CI: 0.57-0.61) for dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), 0.46 (95% CI: 0.44-0.49) for sodium-glucose co-transporter-2 (SGLT2) inhibitors, 0.38 (95% CI: 0.29-0.51) for glucagon-like peptide-1 receptor agonists (arGLP-1), 1.34 (95% CI: 1.31-1.37) for sulfonylurea (SU), and 1.47 (95% CI: 1.43-1.51) for insulin. Anti-COVID-19 vaccination was associated with a lower fatality risk in both DM types: OR = 0.07 (95% CI: 0.03-0.20) in T1DM and OR = 0.19 (95% CI: 0.17-0.22) in T2DM. Conclusions: The results of our study suggest that increased COVID-19-related fatality risk in both T1DM and T2DM patients associated with the male population, older age, longer DM duration, and absence of anti-COVID-19 vaccination. In T2DM, pre-COVID-19 glucose-lowering therapy with metformin, DPP-4 inhibitors, SGLT2 inhibitors, and arGLP-1 had a positive effect on the risk of death. The most vulnerable combination of risk factors for lethal outcome in both DM types was vaccine absence + age ≥65 years + DM duration ≥10 years.

[Modern problems of hyper- and hypoparathyroidism].

The parathyroid glands are the most important regulators of mineral metabolism. The parathyroid glands were first discovered only in 1880 and their function went the long way unrecognized. Even the term "parathyroid gland" itself speaks of the initial misconception of it as an underdeveloped part of the thyroid. To date, there is a large amount of data regarding the role of this endocrine gland in the human body and the significant changes associated with their dysfunction, including such widespread diseases such primary, secondary and tertiary hyperparathyroidism, hypoparathyroidism. This review covers the problem of the main disturbances in calcium-phosphorus metabolism, presents the results of databases of patients with primary hyperparathyroidism and hypoparathyroidism, as well as current epidemiological trends in Russia and in the world.

[Diabetes epidemiology in Russia: what has changed over the decade?]

The National diabetes register (NDR) was created as unified dynamic database in online format. It allows providing clinical and epidemiological monitoring of diabetes mellitus (DM) in the whole country. AIM: To analyze the epidemiological characteristics of diabetes over the past decade, to access the dynamics of the prevalence of acute (coma) and chronic (micro - and macrovascular) complications of DM. MATERIALS AND METHODS: The object of the study was the depersonized NDR database of DM patients. It consists of 84 regions of the Russian Federation (RF), included in the online registry system on 01.01.2019. RESULTS AND DISCUSSION: The total number of patients with DM in RF on 01.01.2019 was 4 584 575 (3.12% of the population), comprising 256.2 thousand patients with T1DM, 4.24 million with T2DM, 89.9 thousand other types of DM. Since 2000, the number of DM patients in RF has grown 2.2 times. 34.7% patients with T1DM reached target level of HbA1c.

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus.

AIM: The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION: Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

[The analysis of association between type 2 diabetes and polymorphic markers in the CDKAL1 gene and in the HHEX/IDE locus].

The increase in diabetes was noted at the turn of the 21st century. Patients with type 2 diabetes (T2DM) make up the majority of patients. Diabetes is a multifactorial disease. It arises from adverse effects of environmental factors on the body of genetically susceptible peoples. According to modern concepts, T2DM is a polygenic disease. Each of the involved genes contributes to the risk of developing of this disease. In our study, the association between polymorphic genetic markers rs7756992, rs9465871, rs7754840, and rs10946398 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus and T2DM in the Russian population were studied. Four hundred forty patients with type 2 diabetes and 264 healthy individuals without any signs of the disease were examined. The comparative analysis of distribution of genotypes and allele frequencies points to an association between polymorphic genetic markers rs7756992, rs9465871, and rs10946398 in the CDKAL1 gene and this disease. For the other polymorphic genetic markers (rs7754840 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus), no statistically significant associations are found. On the basis of these data, we can conclude that the CDKAL1 gene is associated with development of T2DM. For the HHEX/IDE locus, such an association is absent.

[Urinary excretion of markers for podocyte injury in patients with diabetes mellitus]. / Ekskretsiya s mochoi markerov povrezhdeniya podotsitov u bol'nykh sakharnym diabetom.

AIM: To estimate the urinary excretion of markers for podocyte injury, to specify their value for the early diagnosis of diabetic nephropathy (DN), and to access the risk of its progression in patients with diabetes mellitus (DM) with varying degrees of albuminuria/proteinuria. SUBJECT AND METHODS: Seventy-four diabetic patients (30 with type 1 DM and 44 with type 2 DM) were examined and divided into 3 groups according to the urinary concentration in one urinary portion: 1) 41 patients with normal albuminuria (NAU) (<20 mg/l); 2) 13 patients with microalbuminuria (MAU) (20-200 mg/l); 3) 20 patients with proteinuria (PU) (>200 mg/l). A control group included 10 healthy individuals. The urinary levels of the podocyte structural proteins nephrin and podocin were determined by enzyme immunoassay. RESULTS: Nephrinuria (NU) was detected in 63, 77, and 80% of the patients with NAU, MAU, and PU, respectively. Podocinuria (PDU) was found in 78, 54, and 83% of those with NAU, MAU, and PU, respectively. NU in DN with PU was significantly higher than that in DM with NAU. In the NAU, MAU, and PU subgroups, podocin excretion was equally higher and did not differ between the types of DM. There was a direct correlation of NU with albuminuria, which was stronger in the MAU subgroup. In the patients with DM with varying degrees of albuminuria, the values of NU and PDU correlated directly to serum creatinine levels and inversely with glomerular filtration rate. NU directly correlated with glycated hemoglobin levels in the patients with types 1 and 2 DM of less than 5 years' duration and a direct significant correlation of systolic blood pressure with NU was found in those with type 2 DM. CONCLUSION: Determination of urinary nephrin and podocin levels may be used for the early preclinical diagnosis of DN and the monitoring of the glomerular apparatus in DM.

[Polymorphic gene markers of lipid metabolism are associated with diabetic nephropathy in patients with type 1 diabetes mellitus].

In groups of type 1 diabetes mellitus patients with and without clinical signs of diabetic nephropathy (n = 62 and n = 68, respectively), a search was made for associations between diabetic nephropathy and the polymorphic marker epsilon2/epsilon3/epsilon4 of apolipoprotein E gene (APOE), I/D marker of apolipoprotein B gene (APOB), and Ser447Ter marker of lipoprotein lipase-encoding gene (LPL). The risk of diabetic nephropathy was higher in the carriers of allele epsilon3 and genotype epsilon3/epsilon3 of the polymorphic marker epsilon2/epsilon3/epsilon4 of APOE gene as well as in the carriers of allele 1 and APOB genotype/gene (OR = 2.08 and 2.16; 1.91 and 2.11, respectively). Conversely, the carriers of allele D showed a reduced risk of this complication (OR = 0.52). No significant differences in distribution of alleles and genotypes of the polymorphic marker Ser447Ter of LPL gene were found between the groups. Our results indicate that the genes encoding two major components of lipid metabolism are involved in the development of diabetic nephropathy in patients with type 1 diabetes mellitus.

[A search for association between the polymorphic markers of PON1 and PON2 genes and diabetic nephropathy in patients with type I diabetes mellitus].

Alleles and genotypes of polymorphic markers of paraoxonase 1 and paraoxonase 2 genes (PON1 and PON2) encoding enzymes of the body antioxidative defense were compared in type 1 diabetes mellitus patients with or without diabetic nephropathy. The patients with nonoverlapping ("polar") phenotypes constituted different groups. The first group contained patients with diabetic nephropathy (DN+, n = 62), clinical proteinuria (albuminuria above 300 mg per day), and at least 15-year disease duration. In control group, the patients had no diabetic nephropathy (DN-, n = 68), their albuminuria was below 200 mg per day, and disease duration was at least 20 years. Comparative analysis with exact Fisher's test revealed no significant differences in frequencies of alleles and genotypes of the PON1 gene polymorphic marker Gln192Arg and of PON2 gene polymorphic markers Ala148Gly and Cys311Ser. Our results suggest that the polymorphic markers studied are not associated with diabetic nephropathy among Russian patients in Moscow.

[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.