Olga Tkacheva

Gut microbiota and diet in patients with different glucose tolerance

Type 2 diabetes (T2D) is a serious disease. The gut microbiota (GM) has recently been identified as a new potential risk factor in addition to well-known diabetes risk factors. To investigate the GM composition in association with the dietary patterns in patients with different glucose tolerance, we analyzed 92 patients: with normal glucose tolerance (n=48), prediabetes (preD, n=24), and T2D (n=20). Metagenomic analysis was performed using 16S rRNA sequencing. The diet has been studied by a frequency method with a quantitative evaluation of food intake using a computer program. Microbiota in the samples was predominantly represented by Firmicutes, in a less degree by Bacteroidetes. Blautia was a dominant genus in all samples. The representation of Blautia, Serratia was lower in preD than in T2D patients, and even lower in those with normal glucose tolerance. After the clustering of the samples into groups according to the percentage of protein, fat, carbohydrates in the diet, the representation of the Bacteroides turned to be lower and Prevotella abundance turned to be higher in carbohydrate cluster. There were more patients with insulin resistance, T2D in the fat–protein cluster. Using the Calinski–Harabasz index identified the samples with more similar diets. It was discovered that half of the patients with a high-fat diet had normal tolerance, the others had T2D. The regression analysis showed that these T2D patients also had a higher representation of Blautia. Our study provides the further evidence concerning the structural modulation of the GM in the T2DM pathogenesis depending on the dietary patterns.

Age-Related Left Ventricular Changes and Their Association with Leukocyte Telomere Length in Healthy People

Introduction With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length. Methods The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S). Results In the older people there was a higher wall thickness than in the younger (1.03±0.09 vs. 0.88±0.10, p<0.01), whereas LV mass index was comparable between them (85.8±15.40 vs. 83.1±11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (β = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV. Conclusions Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.

Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases

Background Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV). Methods The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis. Results Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL. Conclusions These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk.

Short telomere length is associated with arterial aging in patients with type 2 diabetes mellitus

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. Glucose metabolism assessment tests, measuring intima–media complex thickness and determining the presence of atherosclerotic plaques, pulse wave velocity measurement, and telomere length measurement 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 condition among 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 telomeres may have a protective effect on the vascular wall and may prevent vascular wall deterioration caused by glucose metabolism disorders.

Atorvastatin Therapy Modulates Telomerase Activity in Patients Free of Atherosclerotic Cardiovascular Diseases

Background: Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases (CVDs). Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now, this effect has not been investigated in prospective randomized studies. We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells. Methods: In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35–75 years, free of known CVDs and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction. Results: At study end, 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46 ± 0.05 to 0.68 ± 0.06 (p = 0.004) in the atorvastatin group and from 0.67 ± 0.06 to 0.60 ± 0.07 (p = 0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p = 0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in interleukin-6 within the normal range and a tendency toward reduction in blood urea. Conclusion: These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector. Trial registration: The trial was registered in ISRCTN registry ISRCTN55050065.

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases

Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging. Methods: The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance—HOMA (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as “younger” (m ≤ 45 years, f ≤ 55 years) and “older” (m > 45 years, f > 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis. Results: Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, p < 0.001 for HOMA, p = 0.03 for GH, and p = 0.004 for LTL. In the model with IMT as a dependent variable, p = 0.0001 for HOMA, p = 0.044 for GH, and p = 0.004 for IGF-1. In the model with the number of plaques as a dependent variable, p = 0.0001 for HOMA, and p = 0.045 for IGF-1. In the older group, there were no independent significant associations between GH/IGF-1, LTL, HOMA, and arterial wall characteristics. Conclusions: GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants.

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND REPLICATIVE CELLULAR SENESCENCE: THEIR INTERACTION DURING THE VASCULAR AGEING

The problem of vascular aging is discussed. Special attention among the signs of vascular aging is paid to the activation of the renin-angiotensin-aldosterone system as a source of chronic inflammation and oxidative stress, as well as to its relation to replicative cellular senescence. Potential routes of exposure to these processes are also considered.

PP101. Preeclampsia and pregnancy induced hypertension and carotid artery atherosclerosis.

INTRODUCTION Recent studies indicated preeclampsia (PE) and pregnancy-induced hypertension (PIH) as risk factors for cardiovascular diseases in young women. Women with a history of preeclampsia face double the risk of a heart disease during the 5-15years after pregnancy. We assessed the impact of these factors on endothelial function, atherosclerotic changes and lipid metabolism in young women with a history of preeclampsia and pregnancy-induced hypertension. OBJECTIVES The aim of this study was to examine whether women with a history of preeclampsia more often show signs of atherosclerosis compared with control group METHODS We analyzed serum levels of total cholesterol (TC), HDL-C, LDL-C and triglycerides (TG). Endothelium-dependent vasodilation and carotid artery intima-media thickness (CA-IMT) were evaluated in 18 patients with a history of PE, 16 with a history of PIH and 17 healthy controls (CN). Inter-group differences were calculated using Students t-test. RESULTS We found a worse lipid profile among women with PE and PIH. LDL-C was increased significantly in PE and PIH (PE: 3.17mmol/l [SD 0.50] and PIH: 3.37mmol/l [SD 0.48] vs CN: 2.83mmol/l [SD 0.35], p<0.05); TC and TG were higher in the PE and PIH groups, but not significantly (p>0.05). Compared to controls, endothelium-dependent vasodilation was significantly reduced in PE and PIH patients (10.5% [SD 4.3] and 8.8% [SD 3.1] vs 14.5% [SD 3.6], p<0.05). The mean combined CA-IMT was significantly higher in PE and PIH patients (0.66mm [SD 0.08] and 0.63mm [SD 0.09], respectively vs 0.52mm [SD 0.04]). CONCLUSION We conclude that impaired endothelial vasoreactivity and increased CA-IMT are prevalent in women with a history of PE and PIH and are associated with traditional risk factors that strongly suggest that PE and PIH could be non-traditional cardiovascular risk factors.

Gut Microbiota in Patients with Different Metabolic Statuses: Moscow Study

The aim of this paper was to study gut microbiota composition in patients with different metabolic statuses. Methods: 92 participants aged 25–76 years (26 of whom were men), with confirmed absence of cardiovascular and other chronic diseases (but with the possible presence of cardiovascular risk factors) were included. Carotid ultrasound examinations, 16S rRNA sequencing of stool samples and diet assessments were performed. Statistical analysis was performed using R programming language, 3.1.0. Results: Enterotyping yielded two clusters differentiated by alpha-diversity. Intima-media thickness was higher in the cluster with lower diversity (adj. p < 0.001). Obesity was associated with higher Serratia (adj. p = 0.003) and Prevotella (adj. p < 0.0003) in relative abundance. Abdominal obesity was associated with higher abundance of Serratia (adj. p = 0.004) and Prevotella (adj. p = 0.0008) and lower levels of Oscillospira (adj. p = 0.0005). Glucose metabolism disturbances were associated with higher Blautia (adj. p = 0.0007) and Serratia (adj. p = 0.003) prevalence. Arterial hypertension was associated with high Blautia levels (adj. p = 0.002). The Blautia genus strongly correlated with low resistant starch consumption (adj. p = 0.007). A combination of high-fat diet and elevated Blautia levels was very common for diabetes mellitus type 2 patients (adj. p = 0.0001). Conclusion: The results show that there is a relationship between metabolic changes and higher representation of opportunistic pathogens and low diversity of gut microbiota even in apparently healthy participants.

Prevalence of geriatric syndromes among people aged 65 years and older at four community clinics in Moscow

Background Geriatric syndromes (GSs) are common in older adults and have a significant effect on their quality of life, disability, and use of health care resources. Few studies have assessed the prevalence of GSs in Russia. The aim of this study is to assess the prevalence of GSs among older adults living in the community in Moscow. Methods A cross-sectional study was conducted in four community clinics in Moscow. A total of 1,220 patients completed a screening questionnaire, and 356 of them also underwent a comprehensive geriatric assessment (CGA). Results The mean age of the 1,220 participants was 74.9±6.1 years; 75.5% were women. Based on the questionnaire, 58.3% reported visual or hearing impairment, 58.2% cognitive impairment, 46% mood disorder, 42% difficulty walking, 28.3% urinary incontinence, 21.3% traumatic falls (over the previous year), and 12.2% weight loss. The mean number of GSs per patient was 2.9±1.5. Based on CGA, a decline in Instrumental Activity of Daily Living score was identified in 34.8% of the patients, a risk of malnutrition (Mini-Nutritional Assessment score, 17–23.5) in 25.8%, probable cognitive impairment (Mini-Mental State Examination score <25) in 8.6%, and symptoms of depression (15-item Geriatric Depression Scale score >5) in 36.2%. On the whole, patients demonstrated good mobility (average walking speed, 1±0.2 m/s) and hand grip strength (23.9±6.4 kg in women and 39.1±8.3 kg in men), but poor balance (only 39.4% were able to maintain their balance on one leg for 10 s or more). Conclusion The results of this study demonstrate a high prevalence of GSs among community-dwelling people aged 65 years and older in Moscow. The results provide a better understanding of the needs of older adults in Russia and can facilitate planning for medical and social assistance for this population.