Relationship between indicators of insulin resistance and oxidative balancein adolescents with androgen deficiency

The purpose of the work was to study the relationship between the indicators of insulin resistance (IR), free radical oxidation products (FRO) levels, and the antioxidant system activity in adolescents with androgen deficiency (AD).Materials and methods. 58 adolescents 13­—18 years old with AD were examined. Serum levels of total testosterone, glucose, insulin, tiobarbituric acid active compounds (TBA), carbonylated proteins (CB), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity were determined. The HOMA index and the coefficient of oxidative stress were calculated.Results and discussion. In the group of adolescents with AD without IR, an inverse correlation was found between the HOMA index and CAT activity. CAT activity negatively correlated with CB content and glucose concentration. In addition, an inverse relationship was found between the activity of GPO and SOD. IR indices indirectly, through feedback with the activity of CAT, influence to the formation of conditions for inhibition/activation of FRO of proteins.IR was revealed in 37.9 % of the examined adolescents with AD. Direct relationship was recorded between IR indicators and markers of oxidative stress, as well as between testosterone levels and GPx activity in the group of these patients. Direct correlation between the coefficient of oxidative stress and the content of TBA-­active compounds indicates the formation of oxidative stress due to the activation of lipid peroxidation. Reduced testosterone levels in adolescents with AD inhibits an increase in GPx activity and prevents compensation for excessive intensity of free radical processes. Conclusion. The results indicate that adolescents with AD have a close relationship between the processes of carbohydrate metabolism, FRO, and antioxidant protection.In adolescents with AD without IR, a balancebetween the studied parameterswas found.The formation of IR in adolescents with AD shifts the equilibrium of the oxidative balance towards the activation of FRO processes. Decreased testosterone levels in adolescents with AD do not maintain the body’s antioxidant status within normal limits.

Predictor value of neurohumoral disorders in patients with chronic coronary syndrome with concomitant non-alcoholic fat disease

Annotation. Today it is important to study the clinical and prognostic role of neurohumoral disorders in patients with stable forms of chronic coronary syndrome (CCS) and concomitant liver pathology. The aim of the study: to investigate the levels of markers of insulin, adipokine balance, systemic inflammation and endothelial dysfunction and their predictor value for the presence of non-alcoholic fatty liver disease (NAFLD) in patients with CCS. The prospective monocenter double open study in parallel groups involved 120 patients with CCS: stable angina pectoris II-III functional class aged 60.0 (55.0; 64.0) years, of whom 67 (55%) men and 53 (45 %) women. The control selected group included 30 healthy individuals aged 59.0 (58.0; 66.0) years, including 14 (46%) men and 16 (54%) women. Determination of the serum concentration of biomarkers (adiponectin, resistin, insulin, asymmetric dimethylarginine (ADMA), C-reactive protein) was performed using enzyme-linked immunosorbent assay. Statistical data processing was performed using the license program package “Statistica 13.0” (StatSoftInc, USA, № JPZ8041382130ARCN10-J). The hypothesis about the normality of the distribution of the studied indicators was tested using the Shapiro-Wilk test. Quantitative traits were presented as M ± m or Me (Q25; Q75), depending on the type of distribution. Significance of differences was assessed using Student's t-test (for normal distribution) or Mann-Whitney U-test for independent samples (for distribution other than normal). In order to establish the threshold values of biomarkers for predicting the presence of NAFLD ROC analysis was used. It was found that in patients with CCS with concomitant NAFLD, compared with patients with CCS without liver pathology, there is a significant (p <0,05) increase in insulin levels, HOMA index, resistin, ADMA, RF-C-reactive protein and a decrease in adiponectin concentration. According to the results of ROC analysis, it was found that ADMA (Se = 80.0; Sp = 82.9; AUC = 0.91) had a high sensitivity, the optimal ratio of sensitivity and specificity for the diagnosis of NAFLD among all studied biomarkers. Other biomarkers (HOMA index, adiponectin, resistin, adiponectin/resistin ratio) also had an AUC greater than 0.8, but smaller sensitivity/specificity ratio. Thus, in patients with CCS associated with NAFLD, compared with patients without NAFLD, an imbalance of adipocytokines on the background of insulin resistance, systemic inflammation and endothelial dysfunction is observed. Asymmetric dimethylarginine has the highest sensitivity, the optimal ratio of sensitivity and specificity for the diagnosis of NAFLD in patients with coronary artery disease.

Abstract P166: Kidney Changes In Patients With Morbid Obesity After Bariatric Surgery: Looking For The Mechanisms

Morbid obesity (MO) carries an increased risk of kidney damage. Albuminuria and hyperfiltration decrease after bariatric surgery (BS). The relationships between kidney changes obesity-associated are not fully understood. Aim: to analyze renal changes (Δ) and their determinants at 3-mths after BS (3m-postBS) in patients with MO. Methods: In a cohort of patients with MO, we analyzed changes in renal function at 3m-postBS and possible associations with anthropometric parameters, ambulatory blood pressure, glucose metabolism, adipocytokine profile, and components of both renin-angiotensin-aldosterone and endocannabinoid systems. Results: 59 patients were included, 76% women; age (mean ± SD): 42.3 ± 9.5 years; body weight (mean ± SD): 117.8 ± 19.2 Kg. At 3m-postCxB, significant reductions in body weight and waist circumference were observed (p <0.001), but not in blood pressure. Biochemical changes (mean, 95% CI); eGFR-CKDEPI: -4.6 mL/min/1.73m 2 (-8.6; -0.6), p = 0.024; Na + : 2.5 mmol/L (1.9; 3.0), p <0.001; K + : -0.2 mmol/L (-0.3; -0.1), p = 0.006; HbA1c: -0.47% (-0.63; -0.31), p <0.001 and HOMA-IR-Index: -3.13 (-4.19; -2.06), p <0.001. Δ of Albuminuria: Z-1.8 (p = 0.069). The Δ of eGFR-CKDEPI indirectly correlated only with the Δ of plasma renin activity (PRA), p = 0.026. The Δ of albuminuria indirectly correlated with the Δ of leptin (p = 0.039) and directly with the Δ of HbA1c (0.019), HOMA-index (p = 0.013), ACE2 (p = 0.032) and resistin (p = 0.005), as well as with the Δ of the endocannabinoids N-palmitoyl ethanolamine (p = 0.028) and N-stearoyl ethanolamine (p = 0.022). None of the factors analyzed was associated with changes in sNa + . The reduction in sK + was significantly correlated with the Δ of leptin (p = 0.028) and with the Δ of aldosterone (p = 0.025). In multivariate analyzes, no factor was independently associated with the different markers of renal function. Conclusions: patients with MO experience a decrease in eGFR-CKDEPI associated with an increase in PRA 3m-postBS, indicating that the hyperfiltration present in MO has a hemodynamic origin. On the other hand, the variation in albuminuria is related to the improvement of the carbohydrate metabolism and probably certain cytokines and endocannabinoids have a role, although the latter needs to be confirmed.

Association of Plasminogen Activator Inhibitor-1 and Cardiovascular Events Development in Patients with Prediabetes

Background. Plasminogen activator inhibitor-1(PAI-1) is a marker of endothelial dysfunction(ED) and a predictor of both the development of type 2 diabetes mellitus, and a cardiovascular event(CVE). Its role in the CVE development was sufficiently studied in patients without carbohydrate metabolism disorders, and understudied in patients with prediabetes. Aim: the research interest is the study of PAI-1 in patients with prediabetes and its effect on the CVE development. Materials and methods. The case-control study of 168 patients aged from 18 to 65 was carried out among the local population from January to December 2019.After clinical examination, patients were divided into 3 groups: group 1 (n=55)– patients with prediabetes and with CVE; group 2 (n=93) - patients with prediabetes and without CVE; the control group n=20. Results. Differences in PAI-1 level were found in groups 1 (Me=30718.6 pg/ml) and 2 (Me=24692.0 pg/ml; p≤0.001), even greater differences were found in both groups compared to the control one (p≤0.001). The correlation analysis has found in both group influence such IR indicators as fasting glucose, IR-HOMA index, glucagon, C-peptide to elevation of PAI-1. These findings indicate that with an elevation of the PAI-1 level, the concentration of fasting glucose, glucagon, C-peptide and scores of IR-HOMA index increase in both group. The Binary regression analysis has demonstrated, that an elevation of the PAI-1 biomarker increases the likelihood of CVE by 3.3 fold in patients with prediabetes (p≤0.01). In addition to, a model has been derived for assessing the risk of cardiovascular events in patients with prediabetes. Conclusions. Elevation of PAI-1 concentration is associated with insulin resistance which leads to ED, and further development risk of CVE in patients with prediabetes.

Effects of 60-Day Saccharomyces boulardii and Superoxide Dismutase Supplementation on Body Composition, Hunger Sensation, Pro/Antioxidant Ratio, Inflammation and Hormonal Lipo-Metabolic Biomarkers in Obese Adults: A Double-Blind, Placebo-Controlled Trial

In animals it has been demonstrated that Saccharomyces boulardii and Superoxide Dismutase (SOD) decrease low-grade inflammation and that S. boulardii can also decrease adiposity. The purpose of this study was to evaluate the effect of a 60-day S. boulardii and SOD supplementation on circulating markers of inflammation, body composition, hunger sensation, pro/antioxidant ratio, hormonal, lipid profile, glucose, insulin and HOMA-IR, in obese adults (BMI 30–35 kg/m2). Twenty-five obese adults were randomly assigned to intervention (8/4 women/men, 57 ± 8 years) or Placebo (9/4 women/men, 50 ± 9 years). Intervention group showed a statistically significant (p < 0.05) decrease of body weight, BMI, fat mass, insulin, HOMA Index and uric acid. Patients in intervention and control groups showed a significant decrease (p < 0.05) of GLP-1. Intervention group showed an increase (p < 0.05) of Vitamin D as well. In conclusion, the 60-day S. boulardii-SOD supplementation in obese subjects determined a significant weight loss with consequent decrease on fat mass, with preservation of fat free mass. The decrease of HOMA index and uric acid, produced additional benefits in obesity management. The observed increase in vitamin D levels in treated group requires further investigation.

HDL SUBGROUPS AND THEIR PARAOXONASE-1 ACTIVITY IN THE OBESE, OVERWEIGHT AND NORMAL WEIGHT SUBJECTS

ABSTRACT Background: Obesity and overweight are significant public health problems due to higher risk for coronary artery disease (CAD). It is very important to determine new predictive markers to identify the CAD risk in obese and overweight. To this aim, we analyzed HDL-C subclass and their paraoxonase-1 (PON-1) activity in obese, overweight and normal weight subjects. Method: 71 newly diagnosed obese, 40 overweight and 30 healthy subjects as a control group were enrolled the study. Serum lipids levels were determined with enzymatic colorimetric method. PON-1 activities and HDL-3 levels were determined by spectrophotometric methods. Non-HDL3-C concentrations were calculated with the subtraction of HDL3-C from total HDL-C. Results: The mean serum levels of total HDL-C, HDL3-C, Non-HDL3-C -C and ApoA1 were higher in control group than obese and overweight groups. There were a statistically significant difference between obese and control group in terms of Lp(a), hsCRP and HOMA index. Higher total PON-1, non-HDL3 PON-1 and HDL3 PON-1 activities were found in the control group compared to obese and overweight groups. Total HDL was weakly negative correlated with the HOMA index, BMI and waist circumference. There was a weak negative correlation between non-HDL3-C and waist circumstance. Conclusion: Abnormal HDL-subgroups pattern and decreased PON-1 activities causes increased risk for CVD in obese and overweight individuals. Therefore determination of HDL subgroups and their PON-1 activity improves risk prediction compared with measuring total HDL-C levels and its PON-1 activity alone. Body weight and insulin resistance appear to have a role in the decreased HDL-C levels and PON-1activity in obese.

L-Leucine Supplementation for Preserving Lean Mass During Low Calorie Diet in Sarcopenic Obese Women: A Pilot Study

Background: In sarcopenic obese subjects it is essential to reduce body weight and to preserve lean mass, in order to avoid a worsening of muscle function (1). Several studies have shown that leucine supplementation can be useful to improve skeletal muscle mass in sarcopenic patients (2). Aim: Evaluate the effectiveness of a short-term low calorie diet (LCD) combined with combined supplementation with whey protein, leucine and vitamin D on weight loss, lean mass and muscle strength in sarcopenic, obese, hyperinsulinemic and menopause women. Materials and methods: 16 female with mean age: 58.1 years (range: 47–69 years), BMI 37.6 Kg/m2 (range: 31,7 - 44,1 Kg/m2), HOMA-index ≥ 2.5, were assigned to an LCD regimen (1000 kcal/day) with supplementation of 18 g protein, 4 g leucine and 5 mcg vitamin D for 45 days. Anthropometric indexes, blood and urine chemistry, body composition by DEXA, muscle strength by handgrip test and Short Physical Performance Battery (SPPB) were assessed at baseline and at the end of the treatment. Results: A significant reduction of BMI (35,7 vs 37,6 Kg/m2), waist circumference (102,4 vs 107 cm), HOMA index (2,3 vs 4,8) and fasting insulin (10,4 vs 17,4 μIU/ml) was observed in all patients. Women preserved total lean body mass (57 vs 55 %) and improved significantly muscle strength, as measured by handgrip (22,2 vs 18,6 Kg) and SPPB (8,9 vs 7,5). Conclusion: We conclude that LCD with adequate protein intake and a supplementation with whey protein, leucine and vitamin D should be promoted to maintain muscle mass and improve muscle strength in menopause women with sarcopenic obesity. References: 1. Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018 Sep;14(9):513–5372. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Ceda GP, De Vito G, Donders G, Drey M, Greig C, Holmbäck U, Narici M, McPhee J, Poggiogalle E, Power D, Scafoglieri A, Schultz R, Sieber CC, Cederholm T. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015 Sep 1;16(9)

Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients

Background: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. Methods: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. Results: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). Conclusions: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.

Gender features of changes in clinical and laboratory indicators in patients with acute Q-myocardial infarction complicated by acute heart failure and hyperglycemia on admission

The aim was to determine the gender characteristics of changes in the levels of heart failure markers, neurohumoral stress and blood biochemical parameters in patients with acute Q-myocardial infarction (Q-MI) complicated by acute heart failure (AHF) and hyperglycemia (HG) on admission. Materials and methods. The study involved 84 patients with Q-MI complicated by AHF and HG on admission without a history of diabetes. The average age was 67.00 ± 1.34 years (M ± m). The patients were divided into 2 groups based on gender. Male patients made up the 1 group (n = 52), the mean age was 63.00 ± 1.56 years (M ± m). Group 2 (n = 32) included female patients, the mean age was 78.00 ± 1.81 years. The patients underwent measurements of admission blood glucose level, average glycemia during the first day, glycemic profile (GP) variability, the level of copeptin, NTproBNP, insulin, lipid profile, coagulogram, blood electrolytes, and HOMA index was calculated. On the 12th day, the patients were further examined in order to determine the cause of the HG development. Results. Men had a significantly higher level of standard deviation of HP by 33 %, and average glycemia during the first day by 14 %. There was a tendency towards higher levels of insulin and HOMA-index in male patients compared with women (2.2 times and 1.95 times, respectively). In women, the level of copeptin on day 12 was significantly higher than in men by 2.14 times, and NTproBNP by 2.09 times. In men, there was a tendency towards a decrease in these indicators during the acute period of Q-MI, and the levels of markers increased on the 12th day in women. Troponin I levels in male patients was 2 times higher compared to those in women, but not significantly. No significant differences were found in terms of coagulogram indicators. In women, the level of total cholesterol (TC) on day 1 exceeded that in men by 14 %, on day 12 – by 7 %, the level of low density lipoproteins (LDL) on day 1 – by 18 %, on day 12 – by 17 %. In a dynamic follow-up, the level of TC in men significantly decreased by 10 % (P = 0.002), and in women by 16 % (P < 0.001). The LDL level in men decreased by 17 % (P < 0.001), and in women by 18 % (P < 0.001). Conclusions. The men with acute Q-MI complicated by AHF and HG on admission had significantly higher mean levels of glycemia (by 14 %) and standard deviation of HF during the first day of treatment (by 33 %) as compared to women, and also they showed the tendency to higher levels of troponin I, insulin and HOMA index. Female patients with acute Q-MI complicated by AHF and HG on admission, were found to have significantly higher levels of copeptin (2.14 times) and NTproBNP (2.09 times) on day 12, higher levels of TC and LDL on day 1 (GC by 14 %, LDL by 18 %) and on day 12 (GC by 7 %, LDL by 17 %), but they had better dynamics of the decrease in lipid profile indicators during treatment compared with that in men. Coagulogram indices did not differ significantly depending on the patient gender.

EFFECT OF DYSLIPIDAEMIA AND INSULIN RESISTANCE ON THE COURSE OF ALOPECIA AREATA ASSOCIATED WITH METABOLIC SYNDROME

Alopecia areata (AA) is a tissue-specific disease of the hair follicles, manifested by foci of alopecia on a scalp and other areas of skin. The objective of our study was to evaluate the values of blood lipids and carbohydrate metabolism in patients with АА associated with metabolic syndrome (MS) to determine the relationship between disease severity and metabolic disorders. Materials and methods. Clinical and anamnestic characteristics and laboratory values of lipid spectrum and carbohydrate metabolism were analysed in 50 patients with AA associated with MS. Results. As a result of the study, the following regularities have been established: values of blood lipids (cholesterol, triglycerides, high-density lipoproteins) and carbohydrate metabolism (blood glucose, glycosylated haemoglobin, HOMA index) statistically significantly deteriorate with increasing number of the MS components (p <0.05); in patients with mild AA there is a statistically significantly (p <0.05) smaller number of MS components compared with patients with moderate to severe forms (φemp=2,645 < φcr=1,64); HOMA index increases statistically significantly with increasing severity of the disease: by 14.14% in patients with moderate form compared with patients with mild form, and in the presence of severe form by 28.31% compared with patients with moderate and by 46.46% compared with patients with mild forms of AA (p <0.05); the rate of triglycerides in the blood increases statistically significantly depending on the severity of AA: by 36.17% in patients with moderate form and by 41.78% in patients with severe form compared with mild form of AA (p <0.05); the content of high-density lipoproteins in the blood decreases statistically significantly depending on the severity of AA: by 2.12% in patients with moderate form compared with mild form and by 9.53% in patients with severe form compared with moderate form (p <0.05); no relationship has been found between the severity of MS, given the number of its components, and the stage of AA: active and chronic. Conclusions. As a result of the study, the relationship between the severity of AA and the severity of metabolic disorders in the presence of MS in patients has been established. An important area is the study of correction of dyslipidaemia and insulin resistance in a comprehensive therapy of AA associated with MS.