Rationale. The impact of vitamin D3 deficiency on the risk and prognosis of numerous chronic diseases has been actively studied for years. Recent research has demonstrated that vitamin D is not merely involved in the control of calcium-phosphorus metabolism, but can also enhance insulin sensitivity, decrease the incidence of type 2 diabetes mellitus (T2DM), obesity and autoimmune destruction of pancreatic β-cells. The influence of vitamin D3 on some cardiometabolic risk factors and cardiovascular disease (CVD) was described. Thus studying the role of vitamin D3 in the development of arteries wall changes in T2DM and IR, and their relationship with biology telomere seems to be quite relevant. Aim. To study the relationship between vitamin D3 deficiency and vascular wall condition, telomere biology in patients with varying insulin sensitivity. Materials and methods. The cross-sectional study involved 305 patients (106 men and 199 women) aged 51.5 ± 13.3 y.o. All patients underwent laboratory and instrumental research methods, study of morphofunctional state vascular wall. Telomere length and telomerase activity were determined using polymerase chain reaction. Results. Totally, 18 patients out of 248 (7.2%) were found to have normal vitamin D3 level (more than 30 ng/ml). In 92.8% of those studied Vitamin D3 insufficiency or deficiency was determined. As increase in vitamin D3 deficiency, an increase in fasting glucose was noted, HbA1c and its elevated concentration, HOMA index, glucose disorders up to T2DM, higher vascular stiffness. Telomerase activity in group with vitamin D3 deficiency was significantly lower than in groups with vitamin D3 insufficiency and normal content. Multiple linear regression analysis revealed that they are independently associated with vitamin D3 in T2DM (B=1.43; st. OR. 0.106; p=0.0001), vascular stiffness (B=0.075; st. OR. 2.11; p=0.017), fasting glucose (B=0.169; st. OR 1.62; p=0.004), HbA1c level (B=0.062; st. OR. 7.4; p=0.001) and the presence of “short” telomeres (B=0.09; st. OR. 1.154; p=0.001). ROC analysis revealed relationships between BMI (0.634, p=0.001), duration of T2DM (0.651, p=0.022), high intima media thickness (0.614, p=0.004), vascular stiffness (0.605, p<0.001), HbA1c (0.588, p=0.022) and presence of vitamin D3 deficiency. Conclusion. In persons with varying insulin sensitivity — from insulin resistance up T2DM is advisable assess vitamin D3 levels for effective prevention of arterial wall changes in addition to traditional CVD risk factors. Availability Vitamin D3 deficiency requires active prevention metabolic disorders and vascular changes.

IV (XXVII) Национальный конгресс эндокринологов с международным участием «ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ЭНДОКРИНОЛОГИИ» 22-25 сентября 2021 года СВЯЗЬ ГЕРИАТРИЧЕСКИХ СИНДРОМОВ И ГЛИКИРОВАННОГО ГЕМОГЛОБИНА У ДОЛГОЖИТЕЛЕЙ Браилова Н .В ., Дудинская Е .Н ., Ерусланова К .А ., Шарашкина Н .В,

Anticoagulant and antiplatelet agents are used to prevent stroke and thromboembolic events. There is insufficient data on the effect of these drugs on bone tissue. In addition, the available data are ambiguous, which increases suspicion when used in individuals at high risk of osteoporosis. The article provides data on the effect of anticoagulant and antiplatelet agents on bone metabolism, bone mineral density and the fracture risk. Literature data indicate a negative effect of heparin on bone tissue, which is increase the risk of fractures. Low molecular weight heparins has lower effect on bone tissue than heparin. It is known that vitamin K antagonists significantly affect bone metabolism and markers of bone formation, however, data on the effect on bone mineral density and the risk of fractures are contradictory. Direct oral anticoagulants are relatively safe in relation to bone tissue. Data on the effects of antiplatelet drugs on bone are ambiguous.

This review article deals with the topic of changes in bone tissue in the process of aging of the body. Adipogenesis and osteogenesis are affected at the molecular level, proteins and genes are described, in which somatic mutation can occur during the aging process, resulting in both minor changes and an active loss of bone mineral density. The factors that affect the change in bone mineral density mainly in the elderly, and existing drugs that can slow down osteoporosis are listed. Knowledge of the cellular and molecular mechanisms underlying the aging of bone tissue will contribute to the creation of targeted therapy for osteoporosis, which slows down bone aging and prevents falls and fractures in the elderly people.

Osteoporosis, falls and low-energy fractures have a high prevalence in elderly, which is increasing in the presence of diabetes mellitus type 2 (T2DM). Patients with T2DM have a low rate of bone metabolism, a pronounced change in bone microarchitecture. The use of trabecular bone score in evaluating of densitometry and the FRAX scale improves the sensitivity of the methods in patients with diabetes. Integrated approach is required in elderly patient with type 2 diabetes and includes assessment of geriatric status, diabetes status, correction of multiple complications of diabetes, carbohydrate metabolism, vitamin D deficiency, selection of the most effective hypoglycemic and anti-osteoporetic therapy and development of preventive and treatment methods aimed to reduce falls risk and fractures rate.

Abstract Background Despite the growing interest to the theme, the gut microbiota (GM) composition and functional capacity in relation to cardiovascular diseases (CVD) have been poorly studied. It is not well studied in nonagenarians or centenarians who live much longer than others with postponed CVD. In this study, we assessed GM in association with different metabolic factors in healthy middle-aged adults and the elderly at the turn of a hundred years old. Purpose Our aim was to study GM in a healthy cohort (HC) with different metabolic risk factors and in an extremely elderly cohort (EC) of long livers from our city. Methods The study included HC of 104 untreated subjects aged from 25–76y (52±13) carefully selected through the exclusion of CVD and other chronic diseases by means of clinical (with different specialists consultations to exclude any factors of inflammation) and a wide range of laboratory evaluation, ECG, treadmill test, ECHOCG, carotid artery ultrasound and the second group of 20 long livers 97–100y (98±1). EC underwent a complex geriatric assessment, also a wide range of laboratory evaluation, ECG, ECHOCG, carotid artery ultrasound. GM composition was studied by the V3-V4 16S rRNA sequencing. Taxonomic units were identified with QIIME 1.9.1. Statistical analysis was done by using the Phyton v.3.2 programming language. Metabolic reconstruction was performed with PICRUSt algorithm. All GM analyzes performed with age, sex and FDR adjustments. Results One of the most pronounced differences in GM between groups was a significantly higher representation of antiinflammatory Bifidobacterium genus in long livers (p=0.026 (MaAsLin), LDA=4.304). Among risk factors, high body mass index (BMI) was associated with a high abundance of conditional pathogens of Prevotella genus in HC (p<0.002, GLM) and also in EC (p=0.013, MaAsLin). BMI was correlated with hs-CRP level in EC (p=0.04, rs = 0.634). Median hsCRP in EC was 2.4mg/l (Q3–Q1=5.58), 2.45mg/l (Q3–Q1=2.03) (no significant differences, U-test). Despite this, we found that microbiota of long livers had much higher potential to produce butyrate (anti-inflammatory agent, p=0.016 (MaAsLin), LDA=3.345, PICRUSt algorithm). Average intima-media thickness (IMT) in EC was 1.07±0.16mm, and 0.76±0.2mm in HC, the difference was not significant (p=0.37, t-test). We found the association between the IMT with Serratia (gram negative conditional pathogens) abundance (p=0.009) in HC but not in EC. Butyrate synthesis potential in EC vs HC Conclusions The EC were unexpectedly healthy. Considering the GM analysis, we may propose that EC microbiota protected long livers from the low-grade inflammation and thus protected them from the development of metabolic disorders by producing a high amount of butyrate, one of the most important anti-inflammatory agents in the human body. Conditional pathogens (the inflammation initiators) associated with BMI and IMT as well as butyrate producers may subsequently become a target for cardiovascular prevention. Acknowledgement/Funding Governmental support

Aim. To study the relationship between telomerase activity and parameters of carbohydrate metabolism and vascular wall depending on the type 2 diabetes (T2D).Material and methods. The study included 50 patients with T2D and 139 healthy volunteers. All subjects were assessed for carbohydrate metabolism, chronic inflammation (C-reactive protein (CRP), fibrinogen), endothelial dysfunction, carotid intima-media thickness and number of atherosclerotic plaques by duplex scanning, carotid-femoral pulse wave velocity, lymphocyte telomere length and telomerase activity.Results. In T2D patients, telomerase activity was lower (p=0,039), telomeres were shorter (p=0,031) and CRP level was higher (p=0,031) than in patients without T2D. All patients were divided by telomerase activity. T2D patients with low telomerase activity had higher values of CRP (р=0,016), pulse wave velocity (р=0,010), carotid intima-media thickness (р<0,001) and number of atherosclerotic plaques (р=0,014) than in patients without T2D. There were no significant differences in high telomerase activity group. In the group of patients with/without T2D, there were independent negative relationship between telomerase activity and glycated hemoglobin (p=0,035), fasting plasma glucose (p=0,003), arterial stiffness (p=0,044) and independent positive relationship between telomerase activity and fibrinogen (p=0,027), CRP (p=0,042).Conclusion. Vascular changes, chronic inflammation and cell aging were weightier in patients with T2D. The established relationship between telomerase activity and parameters of carbohydrate metabolism, chronic inflammation and vascular stiffness may indicate the important role of telomerase activity in the development of cardiovascular diseases in T2D patients.

Purpose of the study. To study the relationship between the gut microbiota composition and the levels of the end glycation products precursors in individuals without clinical manifestations of chronic diseases. Materials and methods. The study included 92 participants aged 25 to 76 years without clinical manifestations of severe somatic pathologies not receiving any drug therapy but with the possible presence of risk factors including metabolic disorders. All participants underwent a thorough preliminary examination, which included physical examination, clinical and biochemical blood tests, electrocardiography and treadmill test, applanation tonometry, as well as V3-V4 sequencing of variable regions of the 16S rRNA gene of gut microbiota and analysis of glyoxal and methylglyoxal levels in the blood. Results. The levels of glyoxal and methylglyoxal correlated with each other (r = 0.238, p = 0.0016). Among the clinical parameters, a high level of glyoxal in the blood was associated with an increase of systolic blood pressure (r = 0.24, p <0.002). At the same time, the correlation did not reach the level of confidence in the relationship of glyoxal with the vascular wall rigidity. The result of the analysis of the microbial composition of the gut microbiota was the discovery of relationship between an increase in the level of glyoxal with a high representation of the poorly studied family of gram-positive bacteria Mogibacteriaceae. Without the use of filtration methods of underrepresented genera, the interrelation of Fusobacteria order with a high level of methylglyoxal was also discovered, which, nevertheless, requires further study on larger cohorts. Conclusion. High levels of circulating glycation end products precursors are associated with changes in the composition of the gut microbiota, including an increase in the number of Mogibacteriaceae family.

Aim. To investigate  on  the  presence and  relation characteristics of glycemia  variability (GV) and   vascular   wall  parameters,  chronic inflammation, oxidation status,   telomere  biology in type  2  diabetes patients (DM2). Material and methods . Into the single-movement study, 50 DM2 patients included, with no signs of cardiovascular diseases. All participants  were evaluated on the carbohydrate  metabolism, glycemia variablity, underwent duplex  scan   of  carotid   arteries   with  intima-media  complex  (IMC) measurement, and  assessment for atherosclerotic  plaques;  underwent carotid-femoral pulse wave velocity measurement, endothelium dependent vasodialtion, telomere length measurement and telomerase activity (TA). Results. The parameters of vessel wall, together with the classical CVD risk  factors,   independently   related   with the  various  carbohydrate metabolism parameters: glycated hemoglobin, fasting glucose plasma, HOMA-IR index, C-peptide, immune reactive insulin. The GV of moderate amplitude  of glycemia (MAGE) was related  to IMC increase  in DM2 patients.  There was significant relation of telomere length (TL) not just with a chronic hyperglycemia, but with glucose level fluctuations as well, e.g. with GV standard deviation (SD), MAGE, CONGA (continuous overall net glycemic action), and such relation is higher in the analysis of “the longest”  telomeres.  Relation of TL  and  GV  is not dependent on the cardiovascular risk factors,  chronic inflammation and TA, but depends on fasting plasma glucose.  There was no significant relation of TA with GV in DM2. There was direct correlation of GV CONGA  and oxidative stress marker malonic dialdehyde, and independent negative correlation of GV (MAGE, SD, CONGA) with TL. Conclusion. GV is related  with subclinical atherosclerosis (IMC) and shorter  TL in DM2 patients,  which is mediated  by activated oxidation stress under glycemia fluctuations.

Telomere length (TL) is a recognized marker of replicative cellular ageing, and related to the ageing of cardiovascular system with the risk of cardiovascular diseases development (CVD). Chronic inflammation and oxidative stress significantly determine the velocity of telomeres shortening, and most of CVD risk factors (RF) closely related to these proceses; and it is possible to suggest that relationship of TL and RF determine CVD risk. However, clinical studies on this processes elaboration are lacking.Aim. To study relation of TL with traditional and some “new” RF in persons of different age without clinical signs of CVD, related to atherosclerosis.Material and methods. Totally, 303 patients included, of the age 25-91 y.o., without signs of CVD and other chronic diseases, not taking regularly and medications. All patients underwent traditional and some “novel” RF. TL was measured via real time polymerase chain reaction.Results. According to the regression model, TL is independently related to age, C-reactive protein (marker of inflammation), urea (oxidative stress maker), and metabolic status markers as waist circumference, insulin resistance index HOMA, fasting glucose level; the most significant predictor is HOMA (p=0,0001). Risk of having shortened telomeres increases 12 times with increased urea, 2,4 times with insulin resistance, 2 times in fasting hyperglycemia.Conclusion. Revealing of the factors that are related to cellular ageing makes it to define the most potentially benefit targets for interventions towards early and effective CVD prevention.

Arterial wall status is determined by several characteristics, the main of them are as follows: pulse wave velocity (PWV), carotid arteries intima-media thickness (IMT), the presence of atherosclerotic plaques, endothelium-dependent vasodilation (EDVD). When these parameters change, the risk for cardiovascular disease (CVD) grows. The nature of relationship between these indices in people without CVD clinical signs is understudied, especially in those of older age.Aim. To estimate correlations between different parameters of arterial wall in patients of different age without CVD.Material and methods. A total of 303 people aged 25-91 years without any manifestations of CVD or other chronic diseases and without regular medical treatment were examined. PWV estimation, carotid ultrasound with IMT measurement and atherosclerotic plaques amount calculation and EDVD estimation using reactive hyperemia test were performed. Results. Patients without CVD clinical signs rather often reveal arterial wall lesions already in the younger age group (mean age 40.9±8.7): reduced EDVD – in 26% of the cases, the presence of atherosclerotic plaques – in 22%, increased PWV – in 15%, increased IMT – in 8%. The prevalence of arterial wall alterations in the older age group (mean age 61.19±8.5) increase many-fold. All arterial wall parameters correlate with age. The stronger correlation was revealed between IMT and the amount of atherosclerotic plaques: r=0.46 (р<0.001) in the younger group and r=0.47 (р<0.001) in the older one. We didn’t find any relationship between PWV and EDVD in the younger group and between PWV and the amount of atherosclerotic plaques in the older one. Thickened carotid intima-media increases the risk of arterial stiffness by 2.3 times.Conclusion. Estimation of the state of arterial wall in people of young age without CVD allows detecting individuals who require active CVD prevention. Increased stiffness of arterial wall and the development of subclinical atherosclerosis represent different phenotypes of alterations.

Detection of principal subclinical arterial wall lesions is one of the most important aspects of effective cardiovascular disease (CVD) primary prevention. Such lesions include: arterial wall thickening, increased rigidity, endothelial dysfunction development. However, the role of traditional CVD risk factors in the development of individual arterial wall lesions in CVD-free people is understudied. This is particularly so with people of older age.Aim. To study the role of traditional CVD risk factors in development of arterial wall lesions in relatively healthy individuals of different age.Material and methods. We have examined a total of 303 people aged 25-91 years, with no signs of CVD and other chronic diseases and without any regular medical treatment. Anthropometric parameters, blood pressure, fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels were detected in all the patients. Measurement of pulse wave velocity was conducted using SphygmoCor device (AtCorMedical, Australia). Carotid ultrasound to measure intima-media thickness and number of atherosclerotic plaques was conducted using linear transducer with ultra-high resolution 17-5 MHz (PHILIPS iU22, the Netherlands) in the B-mode. Endothelium-dependent vasodilation was assessed by the reactive hyperemia test.Results. Multivariate linear regression analysis has revealed fasting hyperglycemia and increased systolic blood pressure to be to a greater degree associated with arterial wall state in both age groups. According to the results of multivariate logistic regression analysis a relationship between risk factors and arterial wall parameters is stronger in the younger group as compared with the older one.Conclusion. Systolic blood pressure and fasting hyperglycemia must be the main targets of CVD primary prevention in older age group, while in younger age group other traditional risk factors must be taken into account as well.

Aim. To study the age-related changes in structure of myocardium of the left ventricle and their relation with telomere length. With the age even in absence of cardiovascular diseases (CVD) and risk factors (CRF) there is a changing of the left ventricle (LV) myocardium structure. Probable mechanism of the age-related changes is cell ageing. One of the markers of cell ageing is telomere length (TL) that is also a marker of biological age. Material and methods. After screening we included 303 persons at the age 23-91 y.o. without clinical signs of CVD. All participants underwent transthoracal echocardiography by the standard method. Telomere length was measured in leucocytes on the genomic desoxyribonucleic acid (DNA) by real-time polymerase chain reaction method (PCR). We measured the relative length of telomeres. For the assessment of parameters relations we used correlational logistic regression analysis and build-up of multidimensional regression models. Results. Older age group (women >55 years and men >45 years) of those without significant signs of CVD and CRF comparing to the group of younger persons we found thicker LV myocardium and its concentric remodeling. TL was significantly linked with the age (β=-0,012, p=0,0001). Also we found the relation of TL with LV structure parameters: interventricular septum thickness (IVST) (β=-0,028, p=0,01), relative wall thickness (RVT) (β=-0,012, p=0,02) using the age and CRF. However shorter telomeres (<9,75 units) were not related to the increase of IVST (OR=1,44; 95% CI 0,84-2,47; p=0,18), posterior wall thickness (PWT) (OR=1,56; 95% CI 0,37-6,59; p=0,55) and RVT (HR=1,40; 95% CI 0,74-2,65; p=0,31). Conclusion. Left ventricle hypertrophy and its concentric remodeling in older age group without CVD and CRF shall be regarded as age-related. LT, cell ageing marker, is not related to the age-specific changes of LV structure.

It is known that glucose disturbances contribute to micro-and macrovascular complications and vascular aging. Telomere length is considered to be a cellular aging biomarker. It is important to determine the telomere length role in vascular structural and functional changes in patients with diabetes mellitus. We conducted a cross-sectional observational study in a high-risk population from Moscow, Russia. The study included 50 patients with diabetes and without clinical cardiovascular disease and 49 control group participants. Glucosemetabolism assessment tests, measuring intima-media complex thickness and determining the presence of atherosclerotic plaques, pulse wave velocitymeasurement, and telomere lengthmeasurement were administered to all participants. Vascular changes were more dramatic in patients with diabetes than in the control group, and the telomeres were shorter in patients with diabetes. Significant differences were found in the vascular wall conditionamong diabetes patients, and there were no substantial differences in the arterial structure between patients with ` long' telomeres; however, there were statistically significant differences in the vascular wall condition between patients with ` short' telomeres. Vascular ageing signs were more prominent in patients with diabetes. However, despite diabetes, vascular changes in patients with long telomeres were very modest and were similar to the vascular walls in healthy individuals. Thus, long lymphocyte telomeresmay have a protective effect on the vascular wall and may prevent vascular wall deterioration caused by glucose metabolism disorders.