BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.

AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.

MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA_1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.

RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.

CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.

Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control.

Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods.

Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP.

Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (р<0.001); fasting blood glucose from 9.8 mmol/l (7.4; 11.7) to 7.7 mmol/l (6.4; 8.6) (р<0.001); within-day variability from 35.2% (31.6; 40.9) to 23.5% (19.7; 28.6) (р<0.001); daily insulin dose from 0.98 U/kg/day (0.82; 1.14) to 0.87 U/kg/day (0.75; 1.07) (р=0.002). Sub-groups of patients with DP and RDP demonstrated decrease in fasting blood glucose (from 11.5 mmol/l (9.8; 13.8) to 7.5 mmol/l (6.6; 9.1) (р<0.001)), and late evening blood glucose (from 11.0 mmol/l (10.2; 11.2) to 8.0 mmol/l (6.7; 9.5) (р= 0.03)) correspondently. Achieved levels of glycemic control did not differ between sub-groups of patients initially using glargine or detemir.

Conclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.

Backgraund: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders found during pregnancy. Currently, it is relevant not only to search optimal target levels of glycemia during pregnancy, but also to study the ­effect of different glycemia levels on fetal development and further changes in glucose and lipid metabolism in children.

Aims: To describe perinatal period, physical development and metabolic status of children born to women with GDM and different glucose levels during pregnancy.

Materials and methods: The perinatal period features and anthropometric parameters at birth were evaluated in 300 children born to women with GDM and different levels of glycemia during pregnancy. Over the course two years, 141 children have been evaluated for physical development parameters and glucose and lipid metabolism. Fasting and postprandial glycemia was measured with glucometer for 14 days in 33 children aged 1 to 4 years.

Results: The anthropometric parameters of children at birth did not differ from the parameters of the control group (p> 0.05) when during pregnancy fasting blood glucose was less than 5.1 mmol / l and 7.0 mmol / l 1 hour after a meal. The glycemia in women above this level was associated with an increase of frequency and risk of a body mass index, body mass / length ratio and head circumference “above average” in children at birth (p <0.05). With the dynamic control of anthropometric parameters up to 2 years, no differences between the comparison groups were obtained (p> 0.05). The change in metabolic parameters was represented by neonatal hypoglycemia in children of GDM group (GDM group — 23%, control group — 3.5%, p = 0.000002), the least risk of which occurred in group with the lowest fasting and postprandial glycemic values during pregnancy. Fasting glucose, and insulin levels, НOMA index, triglycerides and cholesterol, as well as monitoring fasting and postprandial glycemia for 14 days, were obtained no significant differences between the comparison groups of children (p> 0.05).

Conclusions: The lowest risks of neonatal hypoglycemia and anthropometric deviations at birth were associated with the lowest glycemia levels during pregnancy, which correspond to the criteria of the Russian clinical guidelines.

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.

Gout and diabetes mellitus are metabolic diseases, the pathogenesis of which is based on an excess of organic molecules in the body, in the first case — uric acid (UA), in the second — glucose. It is assumed that UA can also be involved in the pathogenesis of type 2 diabetes mellitus (T2DM), while insulin resistance and hyperglycemia affect purine metabolism. Both diseases are associated with an increased risk of cardiovascular events. In addition, chronic microcrystalline inflammation, which is absent in asymptomatic hyperuricemia, but is an obligatory component of gout, is probably an independent factor in T2DM, arterial hypertension, and cardiovascular events. The treatment of both diseases is strategically similar: in gout, the goal is to achieve a normal blood MC level, in T2DM — to normalize glycemia, and the frequent combination of these metabolic diseases requires taking into account the effect of drug therapy on concomitant diseases. Most modern antihyperglycemic drugs can affect purine metabolism, which is confirmed by the results of a number of foreign works. At the same time, the effect of T2DM therapy on purine metabolism and gout has not been adequately covered in the domestic literature, which was the purpose of this review.

Sulfonylureas are widely prescribed all over the world, mainly because of their high effectiveness. At the same time, the heterogeneity of the group is obvious, primarily in relation to the effect of drugs on the risk of developing hypoglycemic events. The review presents the results of new studies, including «Comparative effectiveness of gliclazide modified release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes» and results of a model-based meta-analysis of 24 antihyperglycemic drugs for type 2 diabetes, confirming the higher efficacy of modified release gliclazide (gliclazide MB) compared to DPP-4, as well as a low risk of hypoglycemic conditions. The results of recent studies, as well as the results of the ADVANCE and ADVANCE-ON studies, suggest that gliclazide MB is safe to use as a second-line drug, especially in patients with chronic kidney disease.

Today, diabetes is one of the leading medical and social problems. This is due to a pandemic increase in the development of the disease. Eye complications that occur against the background of diabetes are complex. Diabetic damage to the visual organ is the main cause of visual acuity in these patients. One of the serious complications of proliferative diabetic retinopathy is secondary neovascular glaucoma, which is often refractory to treatment and eventually leads to irreversible blindness. Currently, neovascular glaucoma is an important and urgent problem in modern society, as it leads a large number of patients to disability and impaired social adaptation. The paper presents a review of the literature on the current state of the problem of neovascular glaucoma and presents the results of major international studies.

Based on the data of domestic and foreign literature, the authors provide up-to-date information on the incidence, evaluate the clinical manifestations of the disease, paying attention to new methods of diagnosis and treatment. These data allow us to evaluate the effectiveness of modern therapeutic and surgical approaches in the treatment of neovascular glaucoma, as well as its various complications and measures for their prevention.

Iron (Fe) deficiency and hyperglycaemia are both widely found throughout the world among pregnant women. According to the latest data from the American Diabetes Association (ADA), the prevalence of gestational diabetes mellitus (GDM) has increased and reaches 15–20%. Nowadays, there is growing evidence that a link between Fe metabolism and glucose homeostasis exists. The study of changes in the indicators of Fe metabolism in the serum of pregnant women with glucose intolerance and GDM plays an important role in expanding the understanding of the pathogenesis of these conditions. The hypothesis that excess Fe increases the risk of developing GDM has prompted us to review and evaluate the potential relationship between elevated Fe levels and the risk of developing GDM. The aim is to integrate all available data on the correlation between GDM and Fe status in the body. It is increasingly being recognised that excess Fe accumulation in the body is associated with an increased risk of diabetes. There is no available data on the relationship between serum ferritin and GDM in the Russian population, while early identification of the risk of GDM development will be of great importance for its related health effects and prevention. The role of Fe status as a GDM biomarker in high-risk populations is of interest, both for prognostic and diagnostic measures, and for therapeutic interventions. For a better understanding of whether an excess of Fe increases the risk of developing GDM, studies are needed to reveal the role of Fe in the mechanisms of GDM development.

The genetics of Type 2 diabetes a complex metabolic disorder, characterized by decreased insulin secretion and insulin resistance resulting in impaired blood glucose homeostasis remains enigma for geneticists. In 2006 an important step while finding genetic causes of diabetes type 2 was identification of transcription factor 7-like 2 (TCF7L2) gene an important marker in predisposition of type 2 diabetes in almost all ethnic population. Recent genetic research identifies numerous novel type 2 diabetes susceptible genes among these genes TCF7L2 is considered as gang head and emerged as the most promising types 2 diabetes causing gene. Risk variants in TCF7L2 effects pancreatic beta cell development and insulin secretion by influencing Wnt Signaling pathway. Genetic variants in TCF7L2 confer risk for type 2 diabetes by altering expression of transcription factor (which has key role in blood glucose regulation) in pancreas. The purpose of this paper is to evaluate type 2 diabetes susceptible gene the TCF7L2 and to present a comprehensive review of studies carried out worldwide in different ethnic population on association of TCF7L2 polymorphism with type 2 diabetes.