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Background: Given the fact that the studies that examined oxidative stress in relation to obesity that included late adolescents are scarce and show inconclusive results we aimed to investigate a wide spectrum of nitro-oxidative stress biomarkers i.e., malondialdehyde (MDA), xanthine oxidase (XO), xanthine oxidoreductase (XOD), xanthine dehydrogenase (XDH), advanced oxidation protein products (AOPP) and nitric oxide products (NOx), as well as an antioxidative enzyme, i.e., catalase (CAT) in relation with obesity in the cohort of adolescent girls ages between 16 and 19 years old. Methods: A total of 59 teenage girls were included in this cross-sectional study. Binary logistic regression analysis was performed to examine possible associations between bio- chemical and nitro-oxidative stress markers and body mass index (BMI). Results: There were not significant differences between oxidative stress markers between normal weight and overweight/obese girls (i.e., AOPP, XOD, XO, XDH) and CAT, except for MDA (p

Objective: Type 1 diabetes (T1D) mellitus is one of the most frequent autoimmune diseases in childhood. Chronic complications are the main causes of cardiovascular morbidity and mortality in T1D. Although interactions between advanced glycation end products (AGE) and their receptors (RAGE) and transforming growth factor-β1 (TGF-β1) are implicated in development and progression of diabetic micro-and macro-vascular complications, they also have important roles in immune system regulation. Methods: Blood samples were obtained from 156 adolescents with T1D and 80 apparently healthy controls. T1D patients diagnosed with any other autoimmune disease and receiving any kind of drugs except insulin therapy were excluded from this study. Exclusion criteria for controls were positive family history of T1D and drugs/supplements application. TGF-β1 and transmembrane full-length RAGE (flRAGE) messenger ribonucleic acid (mRNA) levels in peripheral blood mononuclear cells (PBMC) were obtained by quantitative polymerase chain reaction (qPCR) method. Circulating levels of biochemical markers, TGF-β1 and soluble RAGE (sRAGE) levels were also determined. Results: TGF-β1 and flRAGE mRNA levels were significantly higher in controls compared to patients (p

Background:Association between endocan and non-traditional anthropometric indices, as distinct cardio -vascular disease risk factors, has not been examined inprevious studies. Endocan is a novel inflammationbiomarker with its higher levels involved in cardiometabolicdiseases development. Taking into consideration thatobesity is an independent risk factor for many cardio -metabolic diseases, we aimed to explore the relationshipbetween endocan levels and novel anthropometric indices i.e., body adiposity index (BAI), cardiometabolic index(CMI), a body shape index, body roundness index, conicityindex, lipid accumulation product index and visceraladiposity index and traditional ones i.e., waist circum -ference, hip circumference, body mass index, waist-to-height ratio and waist-to-hip ratio in adult population.Methods:A total of 177 participants were included.Anthropometric indices and biochemical parametres weremeasured. Results:Univariate regression analysis demonstrated posi-tive correlations of endocan and almost all anthropometricdata. To explore independent associations of endocan andanthropometric parameters, the Model which fulfilled crite-ria for ordinal regression testing was created. Adjusted odds for BAI given in the Model (OR=1.120, 95% CI1.036–1.212, P=0.004), demonstrated that a rise in BAIby 1 unit increased the probability of higher endocan con-centration by 12%. As well, a rise in CMI for 1 unit,increased the probability for higher endocan levels for 2.6times (OR=2.599, 95% CI 1.006–6.712, P=0.049). Atotal of 20.1% of variation in endocan levels could beexplained by this Model.Conclusions:Non-traditional obesity indices, BAI and CMIindependently correlated with higher serum endocan levelsin adult population. Uvod: Povezanost endokana sa netradicionalnim antropometrijskim parametrima, kao različitim faktorima rizika za kardiovaskularne bolesti, nije ispitivana u prethodnim studijama. Endokan je novi biomarker inflamacije, čije su veće vrednosti zabeležene kod kardiometaboličkih poremećaja. Znajući da je gojaznost nezavisan faktor rizika za mnoga kardiometabolička oboljenja, cilj je bio da se ispita povezanost endokana i novih antropometrijskih pokazatelja tj. indeks telesne gojaznosti (BAI), kardiometabolički indeks (CMI), indeks oblika tela, indeks zaokruženosti tela, indeks koniciteta, indeks produkata lipidne akumulacije i indeks visceralne gojaznosti i onih tradicionalnih tj. obim struka, obim kukova, indeks telesne mase, odnos obim struka/telesna visina, odnos obim struka/obim kukova u populaciji odraslih. Metode: Ukupno 177 ispitanika je učestvovalo u istraživanju. Mereni su antropometrijski i biohemijski parametri. Rezultati: Univarijantna regresiona analiza je pokazala pozitivnu korelaciju endokana i skoro svih ispitivanih antropometrijskih parametara. U cilju daljeg ispitivanja postojanja nezavisnih korelacija endokana i antropometrijskih parametara, kreiran je Model koji je zadovoljio kriterijume za ordinalnu regresiju. Prilagođeni Odds-ovi za BAI u Modelu (OR=1,120, 95% CI 1,036-1,212, P=0,004), su pokazali da je porast BAI za 1 jedinicu povećao verovatnoću za porast koncentracije endokana za 12%. Takođe, porast CMI za 1 jedinicu, povećao je verovatnoću za veće vrednosti endokana za 2,6 puta (OR=2,599, 95% CI 1,006-6,712, P=0,049). Ukupno 20,1% varijabiliteta u vrednostima koncentracije endokana može biti objašnjeno ovim Modelom. Zaključak: Netradicionalni pokazatelji gojaznosti, BAI i CMI su nezavisno povezani sa većim vrednostima endokana u populaciji odraslih.

Objective: Oxidative stress is assumed to be the underlying feature of non-alcoholic fatty liver disease (NAFLD). To our knowledge, the mutual involvement of redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS) and oxidative-stress index (OSI)] and cardiometabolic biomarkers in subjects with NAFLD has not been examined yet. Accordingly, we aimed to investigate this potential relationship.Patients and Methods: A total of 122 subjects with NAFLD were compared with 56 participants without NAFLD. The diagnosis of NAFLD was confirmed by abdominal ultrasound. Anthropometric and biochemical parameters were measured. OSI, Castelli’s Risk Index I (CRI-I) and Castelli’s Risk Index II (CRI-II) were calculated. Univariate and multivariate binary logistic regression analysis were used to test the associations between oxidative stress and cardiometabolic markers, respectively and NAFLD. Principal component analysis (PCA) was applied to explore its mutual effect on NAFLD status.Results: Significant positive associations of CRI-I, CRI-II, high sensitivity C-reactive protein (hsCRP) and AOPP with NAFLD were found. PCA analysis extracted 3 significant factors: Oxidative stress-cardiometabolic related factor (i.e., triglycerides, AOPP, HDL-c and HbA1c)-explained 36% of variance; Pro-oxidants related factor (i.e., TOS and PAB)-explained 17% of variance; and Antioxidants related factor (i.e., TAS)-explained 15% of variance of the tested parameters. Moreover, binary logistic regression analysis revealed significant predictive ability of Oxidative stress-cardiometabolic related factor (pConclusion: In addition to oxidative stress (i.e., determined by higher AOPP levels), dyslipidemia (i.e., determined by higher lipid indexes: CRI-I and CRI-II) and inflammation (determined by higher hsCRP) are independently related to NAFLD status. The mutual involvement of pro-oxidants (i.e., TOS and PAB), or the joint involvement of pro-oxidants (i.e., AOPP) and cardiometabolic parameters (i.e., HbA1c, triglycerides and HDL-c) can differentiate subjects with NAFLD from those individuals without this metabolic disorder. New studies are needed to validate our results in order to find the best therapeutic approach for NAFLD.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Defects in trophoblast invasion, differentiation of extravillous trophoblasts and spiral artery remodeling are key factors in PE development. Currently there are no predictive biomarkers clinically available for PE. Recent technological advancements empowered transcriptome exploration and led to the discovery of numerous non-coding RNA species of which microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most investigated. They are implicated in the regulation of numerous cellular functions, and as such are being extensively explored as potential biomarkers for various diseases. Altered expression of numerous lncRNAs and miRNAs in placenta has been related to pathophysiological processes that occur in preeclampsia. In the following text we offer summary of the latest knowledge of the molecular mechanism by which lnRNAs and miRNAs (focusing on the chromosome 19 miRNA cluster (C19MC)) contribute to pathophysiology of PE development and their potential utility as biomarkers of PE, with special focus on sample selection and techniques for the quantification of lncRNAs and miRNAs in maternal circulation.

IntroductionMarkers of iron homeostasis are related to insulin resistance (IR) in adults. However, studies in children and adolescents are scarce and show contradictory results. The aim was to evaluate the potential relationship between iron status markers and IR. Additionally, no previous study has explored the mutual effect of biomarkers of iron homeostasis and inflammation (i.e. high sensitivity C-reactive protein (hsCRP)), and adipokines (i.e. retinol-binding protein 4 (RBP4)) on IR in the cohort of adolescent girls.Material and methodsA total of 60 girls age between 16 and 19 years were included in the study. Serum levels of ferritin, transferrin, soluble transferrin receptor (sTfR), hsCRP, and RBP4 were measured by immunonephelometry. Homeostasis model assessment of insulin resistance (HOMA-IR) and iron homeostasis indexes were calculated. Univariate and multivariate binary logistic regression analysis were used to investigate the possible independent associations of the examined biomarkers. Principal component analysis was used to examine their mutual effect on HOMA-IR in the studied girls.ResultsFerritin, sTfR, hsCRP and RBP4 were significant predictors for higher HOMA-IR in univariate analysis (p = 0.020, p = 0.009, p = 0.007, p = 0.003, respectively). Multivariate regression analysis after adjustment for waist circumference (WC) showed that serum sTfR levels remained positively associated with higher HOMA-IR (p = 0.044). Factorial analysis revealed that the obesity-inflammation related factor (i.e., WC and hsCRP) and adipokine-acute phase protein related factor (i.e., RBP4 and ferritin) showed significant differences between HOMA-IR < 2.5 and HOMA-IR ≥ 2.5.ConclusionsSerum sTfR levels are independently associated with HOMA-IR, whereas higher serum ferritin levels together with higher RBP4 are related to higher HOMA-IR in adolescent girls.

Introduction: We aimed to examine serum endocan level and the summary involvement of dyslipidemia, oxidative stress (OS) and inflammation by calculation of its comprehensive score (i.e. Dyslipidemia-Oxy-Inflammation (DOI) score) in relation to glucoregulation in subjects with prediabetes and overt type 2 diabetes (T2D). Material and methods: A total of 59 patients with prediabetes and 102 patients with T2D were compared with 117 diabetes-free controls. Glycated hemoglobin (HbA1c), inflammation, OS and lipid parameters were measured. Associations of clinical data with HbA1c level were tested with univariate and multivariate logistic ordinal regression analysis. HbA1c as a dependent variable is given at the ordinal level (i.e. < 5.7%; 5.7-6.4%, > 6.4%, respectively). Results: Endocan was significantly higher in the T2D group than in the controls. As endocan concentration rose by 1 unit, the probability for higher HbA1c concentration increased by more than 3 times (OR = 3.69, 95% CI: 1.84-7.01, p < 0.001). Also, a rise in the dyslipidemia score, oxy score, inflammation score and DOI score by 1 unit increased the probability of higher HbA1c concentration by 19%, 13%, 51% and 11%, respectively. In the models, after adjustment for confounding variables, endocan and DOI score remained independent predictors of HbA1c level. Conclusions: Endocan and DOI score are independently correlated with HbA1c in patients with prediabetes and overt T2D.

Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients.This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction.Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p0.001) and TAS (p0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034).Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood.Koronarna arterijska bolest (KAB) je jedan od najvažnijih uzročnika mortaliteta i morbiditeta u širokoj svetskoj populaciji. Dislipidemija, inflamacija i oksidativni stres mogu doprineti poremecaju strukture i funkcije endotela, nastanku ateroskleroze i KAB. Naša studija je imala za cilj da utvrdi da li ekspresije gena Cu/Zn supsoksid dismutaze (Cu/Zn SOD) i Mn superoksid dismutaze (Mn SOD) mogu da budu promenjene pod uticajem oksidativnog stresa kod pacijenata sa KAB.Ova studija je obuhvatila 77 pacijenata sa KAB i 31 naizgled zdravih osoba kod kojih su određeni nivoi serumskih lipida, visoko osetljivi C-reaktivni protein (hsCRP), ukupni antioksidativni status (TAS) i tiobarbituratna kiselina-reagujuće supstance (TBKRS). Ekspresija gena izoenzima SOD određena je u mononuklearnim ćelijama periferne krvi pomoću metode kvantitativne lančane reakcije polimeraze.Nivoi informacione ribonukleinske kiseline (iRNK) Mn SOD su značajno bili niži kod pacijenata sa KAB nego kod kontrole (p=0,011), dok se nivoi Cu/Zn SOD iRNK nisu značajno razlikovali između ispitanih grupa (p=0,091). Kod pacijenata sa KAB utvrđeni su znatno nižinivoi holesterola u lipoproteinima visoke gustine (HDL-h) (p0,001) i TAS (p0,001) i znatno veće koncentracije hsCRP (p=0,002) i TBKRS (p0,001). Postojale su značajne pozitivne korelacije između TAS i iRNK Mn SOD (ρ=0,243, p=0,020) i TAS i iRNK Cu/Zn SOD (ρ= 0,359, p0,001). TBKRS su bile u negativnoj korelaciji samo sa iRNK Cu/Zn SOD (ρ =-0,215, p= 0,040). TAS je bio nezavisni prediktor za nivoe iRNK Mn SOD (OR=2,995, p=0,034).Rezultati ove studije pokazali su da je ekspresija Mn SOD gena smanjena kod pacijenata sa KAB u poređenju sa kontrolnom grupom i da može biti modulirana neenzimskim antioksidativnim statusom u krvi.

BackgroundSpecific metabolic changes during physiological pregnancy are characterized by hyperlipidemia and increased oxidative stress. However, these specific changes raise the question of their pro-atherogenic potential during pregnancy and their influence on the risk of developing cardiovascular disease (CVD) in women later in life, as well as complications during pregnancy. The aim of this study was to investigate the changes in lipid indexes and parameters of lipid peroxidation in non-complicated pregnancy in order to estimate their course of change and potential relationship during non-complicated pregnancy.MethodsThe study included 43 healthy pregnant women and 38 non-pregnant healthy women, in appropriate ages, as the control group. Lipid parameters and oxidative stress parameters were monitored in a longitudinal study in the first, second and third trimesters, and before delivery during non-complicated pregnancy.ResultsResults have shown that lipid indexes rise during pregnancy. The values were significantly increased when compared to the first trimester in all lipid indices and in comparison with the control group. Thyobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were not changed significantly during physiological pregnancy, but LOOH showed a significantly higher value in the first trimester compared with the control group. Prooxidative-antioxidative balance (PAB) significantly increases as pregnancy progresses.ConclusionsWe observed the changes in lipids, lipid indexes and parameters that indicate oxidative modification of lipids in physiological pregnancy that may lead to an atherogenic, prooxidant state.

Nitric oxide (NO) is oxidative stress biomarker which is regarded as one of the key determinants of energy metabolism and vascular tone. Considering the controversial reports on the association between nitric oxide products (NOx) and metabolic syndrome (MetS), the aim of the current study was to examine that potential relationship. Additionally, we aimed to evaluate a broad spectrum of other oxidative stress biomarkers [i.e., malondialdehyde (MDA), advanced oxidation protein products (AOPP), xanthine oxidoreductase (XOD), xanthine oxidase (XO) xanthine dehydrogenase (XDH)] in relation with MetS.A total of 109 volunteers (46.8% of them with MetS) were included in this cross-sectional study. Biohemical and anthropometric parameters, as well as blood pressure, were obtained. The MetS was diagnosed according to the International Diabetes Federation criteria.Multivariate logistic regression analysis showed that XOD (OR=1.011; 95% CI 1.002-1.019; p=0.016), XO (OR=1.014; 95% CI 1.003-1.026; p=0.016), MDA (OR=1.113; 95% CI 1.038-1.192; p=0.003) and AOPP (OR=1.022; 95% CI 1.005-1.039; p=0.012) were the independent predictors of MetS, whereas no association between NOx and MetS was found. As XOD rose for 1 U/L, XO for 1 U/L, MDA for 1 μmol/L and AOPP for 1 T/L, probability for MetS rose for 1.1%, 1.4%, 11.3% and 2.2%, respectively. Adjusted RUnlike XOD, MDA and AOPP, NOx is not associated with MetS.Azot-monoksid (NO) je biomarker oksidativnog stresa i smatra se jednom od ključnih determinanti energetskog metabolizma i vaskularnog tonusa. S obzirom na oprečne rezultate dosadašnjih studija koje se odnose na povezanost između produkata azot-monoksida (NOx) i metaboličkog sindroma (MetS), cilj ove studije je da se ispita njihova potencijalna povezanost. Takođe, cilj je i da se ispita povezanost između širokog spektra ostalih biomarkera oksidativnog stresa [npr., malondialdehida (MDA), produkata uznapredovale oksidacije proteina (AOPP), ksantin oksidoreduktaze (XOD), ksantin oksidaze (XO) i ksantin dehidrogenaze (XDH)] i MetS.Ukupno 109 dobrovoljaca (od kojih je 46,8% ispunjavalo kriterijume za MetS) je uključeno u studiju preseka. Mereni su biohemijski i antropometrijski parametri, kao i krvni pritisak. Dijagnoza MetS-a je postavljena prema kriterijumima Međunarodnog udruženja za dijabetes.Multivarijantna logistička regresija je pokazala da su XOD (OR=1,011; 95% CI 1,002–1,019; p=0,016), XO (OR=1,014; 95% CI 1,003–1,026; p=0,016), MDA (OR=1,113; 95% CI 1,038–1,192; p=0,003) i AOPP (OR=1,022; 95% CI 1,005–1,039; p=0,012) nezavisni prediktori MetS-a, ali postojanje povezanosti između NOx i MetS nije utvrđeno. Sa porastom XOD za 1 U/L, XO za 1 U/L, MDA za 1 μmol/L i AOPP za 1 T/L verovatnoćapojave MetS-a je rasla za 1,1%, 1,4%, 11,3% i 2,2%. Prilagođeni RZa razliku od XOD, MDA i AOPP, NOx nisu povezani sa MetS-om.

Alanine-aminotransferase (ALT) and uric acid cut-off levels used in non-alcoholic fatty liver disease (NAFLD) diagnosis are advised to be lowered. Due to contradictory results on the utility of both these biomarkers for NAFLD screening, we aimed to determine their cut-off levels that can be applied to Montenegrin population with the fatty liver disease.A total of 771 volunteers were enrolled. A fatty liver index (FLI) score ≥60 was used as proxy of NAFLD. The receiver operating characteristic curve analysis with the area under the curve (AUC) was used to determine the cut-off values of ALT and uric acid associated with FLI ≥60.ALT was independent predictor of FLI in both men and women, whereas serum uric acid was its independent predictor only in women. Lower cut-off levels of ALT are associated with the increased prevalence of NAFLD [i.e., ALT was 19 IU/L (AUC=0.746, sensitivity 63%, specificity 72%, P0.001) in women and 22 IU/L (AUC=0.804, sensitivity 61%, specificity 95%, P0.001) in men]. The cut-off value for uric acid was 274 μmol/L (AUC=0.821, sensitivity 68%, specificity 82%, P0.001) in women.Lower cut-off levels of ALT in both genders, and serum uric acid in females, can be reliable predictors of the FLI.Preporuka skorijih studija je da cut-off vrednosti alanin-aminotransferaze (ALT) i mokraćne kiseline budu niže u cilju dijagnostikovanja nealkoholne steatoze jetre. S obzirom na postojanje oprečnih rezultata kada su u pitanju ovi biomarkeri u cilju skrininga na nealkoholnu steatozu jetre, cilj ove studije je bio da se odrede cut-off vrednosti koje bi mogle biti primenjive u crnogorskoj populaciji za dijagnostiku ovog poremećaja.Istraživanje je obuhvatilo ukupno 771 dobrovoljca. Indeks masne jetre (engl. fatty liver index-FLI) ≥60 je korišten za dijagnostikovanje nealkoholne steatoze jetre. ROC analiza i površina ispod krive (engl. area under the curve-AUC) su korišteni za određivanje cut-off vrednosti ALT i mokraćne kiseline, koji su povezani sa FLI ≥60.ALT je nezavisan prediktor FLI kod oba pola, dok je mokraćna kiselina nezavisan prediktor masne jetre samo kod žena. Takođe, niže cut-off vrednosti ALT su povezane sa većom prevalencom pojave masne jetre [za ALT kod žena vrednost je 19 IU/L (AUC=0,746, senzitivnost 63%, specifičnost 72%, P0,001), a kod muškaraca je 22 IU/L (AUC=0,804, senzitivnost 61%, specifičnost 95%, P0,001)]. Cut-off vrednost za mokraćnu kiselinu za pojavu masne jetre kod žena je 274 μmol/L (AUC=0,821, senzitivnost 68%, specifičnost 82%, P0,001).Niže cut-off vrednosti ALT kod oba pola, kao i niže vrednosti mokraćne kiseline kod žena, mogu biti pouzdani prediktori za pojavu masne jetre.

Different byproducts of oxidative stress do not always lead to the same conclusion regarding its relationship with cardiometabolic risk, since controversial results are reported so far. The aim of the current study was to examine prooxidant determinant ((prooxidant-antioxidant balance (PAB)) and the marker of antioxidant defence capacity (total sulphydryl groups (tSHG)), as well as their ratio (PAB/tSHG) in relation to different cardiometabolic risk factors in the cohort of adult population. Additionally, we aimed to examine the joint effect of various cardiometabolic parameters on these markers, since to our knowledge, there are no studies that investigated that issue. A total of 292 participants underwent anthropometric measurements and venipuncture procedure for cardiometabolic risk factors assessment. Waist-to-height ratio (WHtR), body mass index, visceral adiposity index (VAI), and lipid accumulation product (LAP) were calculated. Principal component analysis (PCA) grouped various cardiometabolic risk parameters into different factors. This analysis was used in the subsequent binary logistic regression analysis to estimate the predictive potency of the factors towards the highest PAB and tSHG values. Our results show that triglycerides, VAI, and LAP were positively and high density lipoprotein cholesterol (HDL-c) were negatively correlated with tSHG levels and vice versa with PAB/tSHG index, respectively. On the contrary, there were no independent correlations between each cardiometabolic risk factor and PAB. PCA revealed that obesity-renal function-related factor (i.e., higher WHtR, but lower urea and creatinine) predicts both high PAB ( OR = 1.617 , 95% CI (1.204-2.171), P < 0.01 ) and low tSHG values ( OR = 0.443 , 95% CI (0.317-0.618), P < 0.001 ), while obesity-dyslipidemia-related factor (i.e., lower HDL-c and higher triglycerides, VAI, and LAP) predicts high tSHG values ( OR = 2.433 , 95% CI (1.660-3.566), P < 0.001 ). In conclusion, unfavorable cardiometabolic profile was associated with higher tSHG values. Further studies are needed to examine whether increased antioxidative capacity might be regarded as a compensatory mechanism due to free radicals’ harmful effects.

Introduction/Objective Given the contradictory results regarding the association of liver function biomarkers [e.g., alanine-aminotransferase (ALT), gamma-glutamyl transferase (GGT) and total biliru-bin)] and the risk of cardiovascular disease (CVD), we aimed to explore the relationship between these biomarkers and Framingham risk score (FRS), an established tool used in the prediction of 10-year CVD risk in the cohort of women.Methods A total of 278 women participated in this cross-sectional study. Anthropometric, biochemical parameters, and blood pressure were obtained.Results There was a significant increase in ALT and GGT activity, as well as a decrease in total bilirubin level in the high-risk FRS group compared to moderate-, and low-risk FRS (p for trend = 0.025, p < 0.001, p < 0.001, respectively). Multivariate logistic regression analysis showed that body mass index, triglycer-ides, creatinine, and high sensitivity C-reactive protein levels were the independent predictors of FRS in women [odds ratio (OR) = 1.234, p = 0.001; OR = 2.856, p = 0.001; OR = 1.090, p = 0.002, and OR = 1.295, p = 0.045, respectively]. In contrast, total bilirubin, ALT and GGT lost their independent predictions for high CVD risk. Увод/Циљ С обзиром на контрадикторне резултате који се односе на повезаност биомаркера функције јетре [аланин-аминотрансферазе (АЛТ), гама-глутамил трансферазе (ГГТ) и укупног билирубина)] и ризика за појаву кардиоваску-ларних болести, циљ студије је био да се испита повезаност између ових биомаркера и Фрамингхамског скора за ризик (ФСР), алгоритма за процену 10-годишњег ризика за појаву кардиоваскуларних болести у кохорти женске популације. Методе У овој студији пресека учествовало је укупно 278 жена. Мерени су антропометријски, биохемијски параметри и крвни притисак. Резултати Уочен је статистички значајан пораст активности АЛТ и ГГТ, као и пад вредности укупног билирубина у групи са високим статусом ФСР, у поређењу са средњим и ниским ФСР (p = 0,025, p < 0,001, p < 0,001, редом). Мултиваријантна логистичка регресиона анализа показала је да су индекс телесне масе, вредности триглицерида, креатинина и висо-коосетљивог c-реактивног протеина независни предиктори ФСР код жена (OR = 1,234, p = 0,001; OR = 2,856, p = 0,001; OR = 1,090, p = 0,002 и OR = 1,295, p = 0,045, редом). С друге стране, укупни билирубин, АЛТ и ГГТ су изгубили независну предикцију за високи ризик за појаву кардиоваскуларних болести.

Obstructive sleep apnea (OSA) as a worldwide prevalent condition carries risk for cardiovascular and metabolic diseases, ultimately increasingoverall mortality rates. Non-alcoholic fatty liver disease (NAFLD) can be considered as the primary metabolic disease, but also as a coexisting OSA comorbidity. Although prevalence of NAFLD covers quarter of world population, it increases with OSA presence. It can be speculated that chronic intermittent hypoxia (CIH) and sympathetic nervous system overactivity are involved in NAFLD pathogenesis and progression from simple steatosis throughsteatohepatitis to fibrosis. CIH provides the environment for liveroxidative stress, inflammation and increases the expression of genes involved in cholesterol and fatty acids synthesis. Catecholamines increase β-oxidation in liver and release free fatty acids from adipose tissue in plasma which inhibit insulin effects. Obesity and insulin resistance as key playersin NAFLD development and advancement, deepen vicious circle of oxidative stress, inflammation and dyslipidemia. If not treated, OSA in NAFLD patients has been associated with inflammation, hepatocytes’ necrosis, and fibrosis. Continuous positive airway pressure (CPAP) represents gold standard for OSA therapy, allowing the unimpeded air passage through upper parts of respiratory system. However, it has been demonstrated that CPAP therapyhave beneficial effects on cardiometabolic outcomes and slowliver degeneration Opstruktivna apneja u snu (OSA) kao oboljenje prevalentno u svetu nosi rizik za nastanak kardiovaskularnih i metaboličkih bolesti, povećavajući ukupnu smrtnost. Bolest nealkoholne masne jetre (eng. non-alcoholic fatty liver disease -NAFLD) se može smatrati primarnom metaboličkom bolešću, ali kao i komorbiditet OSA. Iako prevalenca NAFLD obuhvata četvrtinu svetske populacije, ona se povećava sa prisustvom OSA. Pretpostavlja se da su hronična intermitentna hipoksija (eng. chronic intermittent hypoxia -CIH) i prekomerna aktivnost simpatičkog nervnog sistema uključeni u patogenezu NAFLD i progresiju od steatoze preko steatohepatitisa do fibroze. U jetri CIH stvara uslove za oksidativni stres, inflamaciju i povećava ekspresiju gena koji učestvuju u sintezi holesterola i masnih kiselina. Kateholamini stimulišu b-oksidaciju masnih kiselina u jetri i oslobađaju slobodne masne kiseline iz masnog tkiva u plazmu, koje inhibiraju dejstva insulina. Gojaznost i insulinska rezistencija kao ključni faktori u razvoju i napredovanju NAFLD produbljuju začarani krug oksidativnog stresa, inflamacije i dislipidemije. Ako se ne leči, OSA kod pacijenata sa NAFLD je povezana sa inflamacijom, nekrozom hepatocita i fibrozom. Kontinuirani pozitivni pritisak vazduha (eng. continuous positive airway pressure -CPAP) predstavlja zlatni standard u terapiji OSA, koji omogućava neometani prolaz vazduha kroz gornje delove respiratornog sistema. Međutim, CPAP terapija je pokazala da ima povoljne efekte na kardiometaboličke ishode i da usporava degeneraciju jetre.

Introduction: MicroRNAs have a significant role in the pathogenesis of preeclampsia. Circulating microRNAs could represent a potential biomarker for preeclampsia. The aim of this study was to evaluate plasma miR210-3p and miR518b in preeclampsia and healthy pregnancy for the first time by digital droplet PCR (ddPCR). Methods: Thirty-six pregnant women (seventeen healthy pregnancies, nineteen preeclampsia patients) were involved from the Clinic for Gynaecology and Obstetrics “Narodni front” in Belgrade, Serbia. Plasma miR210-3p, miR518b and cel-miR-39 as a spike-in control were measured by ddPCR. Results: MiR518b was significantly elevated in preeclampsia compared to a healthy pregnancy (P = 0.034; 0.302(0.217–0.421) vs. 0.171(0.110–0.266)). MiR210-3p showed no significant difference between the two groups (P = 0.951). The adjustment of miR518b was made for a gestational age and smoking status and the difference between the preeclampsia and healthy pregnancy group was more significant (P = 0.026; 0.300(0.216–0.419) vs. 0.172(0.121–0.245)). Plasma miR-518b was significantly higher in the group of preeclampsia patients with proteinuria above the 75th percentile for the group (P=0.033), in women who smoked (P=0.039), and was positively related to uric acid in preeclampsia (P = 0.018, r = 0.536). Plasma miR518b was able to significantly discriminate between preeclampsia and healthy pregnancy, yielding AUC of 0.712 (95%CI:0.539–0.891), P = 0.028. Conclusions: In this study plasma microRNA were measured for the first time in preeclampsia and healthy pregnancies with ddPCR. Placenta-specific miR-518b could serve as a potential biomarker for discriminating preeclampsia and healthy pregnancy, which should be confirmed on a larger study population. This study has failed to confirm the same potential for miR210-3p. This article has been corrected. Link to the correction: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3669]

Studies that evaluated endocan levels in nonalcoholic fatty liver disease (NAFLD) and liver fibrosis are scarce. We aimed to explore endocan levels in relation to different stages of liver diseases, such as NAFLD, as determined with fatty liver index (FLI) and liver fibrosis, as assessed with BARD score. A total of 147 participants with FLI≥60 were compared with 64 participants with FLI

Reynolds Risk Score (RRS) is regarded as a good screening tool for cardiovascular disease (CVD) risk. Since CVD is the leading cause of death in Montenegro, we aimed to assess the risk of CVD as assessed by RRS and to examine its association with cardiometabolic parameters in apparently healthy middle-aged population. In addition, we aimed to test whether obesity had an independent influence on RRS. A total of 132 participants (mean age 56.2±6.73 years, 69% females) were included. Body mass index (BMI), waist circumference (WC), blood pressure (BP) and biochemical parameters (fasting glucose, insulin, lipid parameters, creatinine and high sensitivity C-reactive protein) were determined. Insulin resistance (HOMA-IR) and glomerular filtration rate (eGFR) were calculated. Compared with females, a significantly higher number of males were in the high RRS subgroup (χ2=45.9, p, Reynoldsov zbir rizika (Reynolds Risk Score, RRS) se smatra dobrim algoritmom probira za procjenu rizika od kardiovaskularnih bolesti (KVB). Kako su KVB vodeći uzrok smrtnosti u Crnoj Gori, cilj studije je bio procijeniti KV rizik primjenom algoritma RRS i ispitati njegovu povezanost s kardiometaboličkim čimbenicima rizika u populaciji odraslih zdravih ispitanika. Cilj je također bio ispitati nezavisan utjecaj pretilosti na RRS. U studiju su bile uključene 132 osobe srednje dobi od 56,2±6,73 godine; 69% su bile žene. Mjereni su sljedeći parametri: indeks tjelesne mase, obim struka, krvni tlak te biokemijski parametri (glikemija natašte, inzulin, lipidni parametri i visoko osjetljiv C-reaktivni protein). Izračunata je inzulinska rezistencija (HOMA-IR) i procijenjena razina glomerularne filtracije (eGFR). U usporedbi sa ženama, značajno veći broj muškaraca bio je u skupini s većim KV rizikom (χ2=45,9; p

Since there is a high prevalence of type 2 diabetes mellitus (DM2), as well as CVD in Montenegro, we aimed to estimate CVD risk by United Kingdom Prospective Diabetes Study (UKPDS) risk engine algorithm in individuals with DM2. Furthermore, we aimed to explore whether non-traditional biomarker such as high sensitivity C-reactive protein (hsCRP) is superior for CVD risk prediction over old traditional risk factors. A total of 180 participants with DM2 (of them 50% females) were included in the current cross-sectional study. Biochemical and anthropometric parameters, and blood pressure were obtained. More males than females were classified at high UKPDS risk category (p

In this randomized controlled pilot trial, we investigated the effects of a 6-month intake of hydrogen-rich water (HRW) on several molecular and phenotypic biomarkers of aging in older adults aged 70 years and over. Forty older adults (20 women) were randomly allocated in a parallel-group design to receive 0.5 L per day of HRW (15 ppm of hydrogen) or control drink (0 ppm of hydrogen) during a 6-month intervention period. The biomarkers assessed at baseline and 6-month follow up were molecular markers in the blood (DNA and chromosomes, nutrient sensing, protein, and lipid metabolism, oxidative stress and mitochondria, cell senescence, inflammation), brain metabolism, cognitive functioning, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life. The mean age, weight, and height of study participants were 76.0 ± 5.6 years, 78.2 ± 16.1 kg, height 167.5 ± 11.5 cm, respectively. A significant treatment vs. time interaction was found for telomere length (P = 0.049), with the length increased after HRW intervention (from 0.99 ± 0.15 at baseline to 1.02 ± 0.26 at follow up) and decreased after drinking control water (from 0.92 ± 0.27 to 0.79 ± 0.15). A marker of DNA methylation (Tet methylcytosine dioxygenase 2, TET2) expression at 6-month follow-up increased in both groups, yet the degree of elevation was significantly higher in HRW (from 0.81 ± 0.52 at baseline to 1.62 ± 0.66 at follow up) comparing to the control water (from 1.13 ± 0.82 to 1.76 ± 0.87) (P = 0.040). A strong trend for treatment vs. time interaction was found for a degree of DNA methylation (P = 0.166), with the methylation increased in the HRW group (from 120.6 ± 39.8 ng at baseline to 126.6 ± 33.8 ng at follow up) and decreased after taking control water (from 133.6 ± 52.9 ng to 121.2 ± 38.4 ng). HRW was superior to control water to increase brain choline and NAA levels in the left frontal grey matter, brain creatine at the right parietal white matter, and brain NAA at the right parietal mesial grey matter (P < 0.05). No significant differences were found between interventions for other outcomes (P > 0.05), except for a significantly improved chair stand performance after HRW intervention compared to the control water (P = 0.01). Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803).

Xanthine oxidase (XO) is an important enzyme responsible for conversion of purine bases to uric acid and represents the major source of reactive oxygen species (ROS) production in circulation. Since pathophysiological mechanism of the relationship between XO activity and urinary albumin excretion (UAE) rate is not well elucidated, we aimed to investigate this association in patients with diabetes mellitus type 2 (DM2). In addition, we wanted to examine whether uric acid itself plays an independent role in albuminuria onset and progression, or it is only mediated through XO activity. A total of 83 patients with DM2 (of them 56.6% females) were included in this cross-sectional study. Anthropometric, biochemical parameters and blood pressure were obtained. Multivariate logistic regression analysis showed that uric acid and XO were the independent predictors for albuminuria onset in patients with DM2 [odds ratio (OR) 1.015, 95% CI (1.008-1.028), p = 0.026 and OR 1.015, 95% CI (1.006-1.026), p = 0.040, respectively]. Rise in uric acid for 1 mu mol/L enhanced the probability for albuminuria by 1.5%. Also, elevation in XO activity for 1 U/L increased the probability for albuminuria for 1.5%. A total of 66.7% of variation in UAE could be explained with this Model. Both XO and uric acid are independently associated with albuminuria in diabetes. Better understanding of pathophysiological relationship between oxidative stress and albuminuria could lead to discoveries of best pharmacological treatment of XO- and/or uric acid-induced ROS, in order to prevent albuminuria onset and progression.

Introduction/Aim Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in individuals with type 2 diabetes mellitus (DM2), we aimed to investigate the potential benefit of determining markers of oxidative stress, inflammation and dyslipidemia for prediction of NAFLD, as estimated with fatty liver index (FLI) in individuals with DM2. Methods A total of 139 individuals with DM2 (of them 49.9% females) were enrolled in cross-sectional study. Anthropometric and biochemical parameters, as well as blood pressure were obtained. A FLI was calculated. Results Multivariate logistic regression analysis showed that high density lipoprotein cholesterol (HDL-c) and malondialdehyde (MDA) were independent predictors of higher FLI [Odds ratio (OR)=0.056, p=0.029; and OR=1.105, p=0.016, respectively]. In Receiver Operating Characteristic curve analysis, the addition of fatty liver risk factors (e. g., age, gender, body height, smoking status, diabetes duration and drugs metabolized in liver) to each analysed biochemical parameter [HDL-c, non-HDL-c, high sensitivity C-reactive protein (hsCRP), MDA and advanced oxidant protein products (AOPP)] in Model 1, increased the ability to discriminate patients with and without fatty liver [Area under the curve (AUC)=0.832, AUC=0.808, AUC=0.798, AUC=0.824 and AUC=0.743, respectively]. Model 2 (which included all five examined predictors, e. g., HDL-c, non-HDL-c, hsCRP, MDA, AOPP, and fatty liver risk factors) improved discriminative abilities for fatty liver status (AUC=0.909). Even more, Model 2 had the highest sensitivity and specificity (89.3% and 87.5%, respectively) together than each predictor in Model 1. Conclusion Multimarker approach, including biomarkers of oxidative stress, dyslipidemia and inflammation, could be of benefit in identifying patients with diabetes being at high risk of fatty liver disease.

Osteoporosis is characterised by reduced bone mineral density (BMD), increased bone fragility and risk of fractures. We investigated clinical significance of bone turnover biomarkers determination for the prediction of fracture risk and response to therapy. We performed three months follow-up study in 48 women with osteoporosis. During the follow-up period 32 patients were on antiresorptive and 16 patients received anabolic therapy. Serum alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide of collagen type I and vitamin D were measured before and 3 months after initiation of the therapy. Higher osteocalcin and ALP levels were significantly associated with increased risk of BMD loss. Following antiresorptive therapy levels of C-terminal telopeptide (P lt 0.001) and osteocalcin (P lt 0.001) significantly decreased. Anabolic therapy significantly increased osteocalcin (P lt 0.01). At the study entry 25.5% of the patients had optimal levels of 25(OH)D and 17% had severe vitamin D deficiency. Vitamin D supplementation during three months improved vitamin D status of the patients (P lt 0.001). In conclusion, our data indicate that osteocalcin and C-terminal telopeptide determination may be useful for BMD loss prediction and monitoring of osteoporosis therapy. This study confirmed importance of vitamin D testing in osteoporosis in order to detect the patients with deficiency and determine the need for supplementation. Osteoporoza se karakteriše smanjenom mineralnom gustinom kostiju, što povećava fragilnost kostiju i rizik za nastanak fraktura. U ovoj studiji pratili smo 48 pacijentkinja sa osteoporozom tokom tri meseca sa ciljem da utvrdimo značaj određivanja koštanih biomarkera u proceni rizika od fraktura i praćenju terapije osteoporoze. Tokom trajanja studije 32 pacijentkinje su bile na antiresorptivnoj, a 16 na anaboličkoj terapiji. Svim pacijentkinjama odredili smo aktivnost alkalne fosfataze (ALP) i koncentracije osteokalcina, C-terminalnog telopeptida kolagena tip I i vitamina D u serumu pre i tri meseca nakon uvođenja terapije. Sa povećanjem nivoa osteokalcina i ALP rastao je rizik za smanjenje mineralne gustine kostiju (BMD). Antiresorptivna terapija dovela je do značajnog smanjenja koncentracija C-terminalnog telopeptida (P lt 0,001) i osteokalcina (P lt 0,001). Tokom anaboličke terapije nivo osteokalcina je značajno porastao (P lt 0,01). Na početku studije 25,5% pacijentkinja je imalo optimalne koncentracije 25(OH)D u serumu, a tešku deficijenciju 17% žena. Nakon 3 meseca suplementacije većina je poboljšala status vitamina D (P lt 0,001). Naši rezultati ukazuju da određivanje osteokalcina i C-terminalnog telopeptida može biti korisno za predviđanje rizika za smanjenje BMD i praćenje efekata terapije osteoporoze. Takođe, potvrđena je važnost određivanja koncentracije 25(OH)D za procenu statusa vitamina D u osteoporozi, u cilju otkrivanja pacijenata sa insuficijencijom i utvrđivanja potrebe za suplementacijom.

Background: Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Methods: Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin’s concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Results: Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Conclusions: Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin’s secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features. © 2019 International Union of Biochemistry and Molecular Biology

BACKGROUND: It is known that non-alcoholic fatty liver disease (NAFLD), and in particular non-alcoholic steatohepatitis, can progress to advanced fibrosis. However, pathophysiological mechanisms implicated in this evolution are not elucidated yet. We aimed to investigate the independent predictors of liver fibrosis in patients with NAFLD, determined by BARD score, one of the most used algorithms for fibrosis evaluation. METHODS: This prospective study enrolled a total of 301 participants with NAFLD, as determined by a Fatty Liver Index (FLI) >= 60. All patients were categorized into two groups: with no/mild fibrosis (BARD score 1, N.=62) and with advanced fibrosis (BARD score 2, 3 and 4 N.=239). RESULTS: Serum high density lipoprotein cholesterol (HDL-c), glucose and glycated hemoglobin were higher (P=0.028, P lt 0.001 and P=0.002, respectively), whereas serum transaminases and gamma glutamil transferase levels were lower in patients with advanced fibrosis than in those with no/ mild fibrosis (P=0.010, P lt 0.001 and P=0.005, respectively). There were no significant differences in oxidative stress (i.e., advanced oxidant protein products and malondialdehyde) and anti-oxidative protection markers (i.e., catalase) between patients with no/ mild fibrosis and advanced fibrosis. Multivariate ordinal regression analysis showed independent associations and predictions of ages (OR=1.071, 95% CI 1.004-1.097, P lt 0.001), and HDL-c levels (OR= 2.549, 95% CI 1.087-5.989, P=0.032) on BARD score categories in patients with NAFLD. CONCLUSIONS: In conclusion, we found that older age and higher HDL-c, are independent predictors for advanced liver fibrosis assessed with the BARD score. Future investigations are needed to further explore this relationship.

Background Retinol-binding protein 4 (RBP4) and cystatin C are regarded as novel metabolic risk markers. Therefore, we aimed to examine which one of these biomarkers better correlates with metabolic syndrome (MetS) in a cohort of postmenopausal women. Methods A total of 129 postmenopausal women (among which 62 women had MetS) were recruited in this cross-sectional study. MetS was diagnosed according to the International Diabetes Federation criteria. Results Cystatin C and RBP4 levels were significantly higher in women with MetS, compared to those without MetS (p=0.011 vs. p2=5.1, p=0.025, and χ2=11.1, p=0.001, respectively). Logistic regression analysis revealed a borderline significant relationship between cystatin C and MetS (p=0.066), but this significance disappeared after adjustment for age, inflammation level and duration of menopause (p=0.221). On the contrary, a significant relationship between RBP4 and MetS was observed not only without adjustment (p=0.009), but also even after adjustment for age, inflammation level and duration of menopause (p=0.006). Conclusions RBP4 better correlates with MetS than cystatin C in postmenopausal women.

Background Chronic renal failure, particularly end-stage renal disease, is a serious health problem associated with a high mortality rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Aims To examine superoxide dismutase isoenzyme gene expression in peripheral blood mononuclear cells of patients on hemodialysis and to determine the associations between superoxide dismutase isoenzyme gene expression, oxidative stress, and non-enzymatic antioxidative protection. Study Design Case control study. Methods This study included 33 patients on hemodialysis (age, 55.33±15.31 years old) and 33 apparently healthy controls (age, 45.37±8.92 years old). Superoxide dismutase isoenzyme messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. General biochemical parameters, high sensitivity C-reactive protein, total antioxidant status, thiobarbituric acid-reactive substances, and the superoxide anion radical were also determined. Results Normalized Cu/Zn superoxide dismutase and Mn superoxide dismutase messenger ribonucleic acid levels were significantly higher in patients than controls (p

Purpose: The pathophysiological mechanism of the relationship between xanthine oxidase (XO) activity and obesity has not been completely elucidated. Since inflammation and oxidative stress are regarded as key determinants of enlarged adipose tissue, we aimed to investigate the association between oxidative stress (as measured with XO activity), inflammation [as measured with high-sensitivity C-reactive protein (hsCRP)] and obesity [as measured with body mass index (BMI)]. In addition, we wanted to examine whether hsCRP itself plays an independent role in XO activity increase or it is only mediated through obesity. Methods: A total of 118 overweight/obese volunteers (mean age 54.76 ± 15.13 years) were included in the current cross-sectional study. Anthropometric, biochemical parameters, and blood pressure were obtained. Results: Significant differences between age, BMI, waist circumference, concentrations of uric acid and hsCRP, as well as xanthine dehydrogenase (XDH) activities were evident among XO tertile groups. Multiple linear regression analysis revealed that BMI (beta = 0.241, p = 0.012) and XDH (beta = − 0.489, p < 0.001) are the independent predictors of XO activity (R2-adjusted = 0.333), whereas hsCRP lost its independent role in XO activity prediction. Conclusion: Obesity (as determined with increased BMI) is an independent predictor of high XO activity in overweight/obese population. Level of Evidence: Level V: cross-sectional descriptive study.

Background Visceral adiposity index (VAI) and Lipid accumulation product (LAP) are novel visceral adiposity indexes, proposed for the evaluation of cardiometabolic risk in adult population. Considering contradictory results obtained from many studies so far, we aimed to examine the potential benefit of applicability of VAI and LAP, over simple anthropometric indices and traditional lipid parameters in individuals with type 2 diabetes mellitus (DM2). Methods A total of 180 DM2 (of them 50% females) and 119 controls who volunteered to participate in this cross-sectional study were enrolled. Anthropometric and biochemical parameters, as well as blood pressure were obtained. VAI and LAP were calculated. Results Multivariate logistic regression analysis showed that high-density lipoprotein cholesterol (HDL-c), (P

Aim: Retinol-binding protein 4 (RBP4) is a novel adipokine closely related to insulin resistance. However, data on the influence of menopausal status on serum RBP4 are scarce. Therefore, the aim of the current study was to examine whether RBP4 levels are associated with menopausal status per se, independently of insulin resistance. Methods: A total of 30 premenopausal and 100 postmenopausal women non-treated with medications were included in the cross-sectional study. Anthropometric and biochemical parameters, as well as blood pressure (BP) were obtained. The homeostasis model assessment of insulin resistance (HOMA-IR) and estimated glomerular filtration rate (eGFR) were calculated. Results: Postmenopausal women displayed higher RBP4 and an unfavorable cardiometabolic profile, compared to premenopausal ones. Multiple linear regression analysis showed that in addition to high triglycerides level (beta=0.315; p=0.002), decreased eGFR (beta=-0.258; p=0.004) and high systolic BP (beta=0.418; p=0.028), menopause per se is an independent predictor of higher RBP4 levels (beta=0.240; p=0.016), (R2-adjusted=0.310; F=6,522; p lt 0.001). Conclusions: Serum RBP4 levels are dependent of menopausal status, which should be taken into account when examining the role of this adipokine in cardiometabolic diseases' occurrence. Cilj: Retinol-vezujući protein 4 (RBP4) je novi adipokin, usko povezan sa insulinskom rezistencijom. Međutim, nema dovoljno podataka u literaturi o uticaju menopauze na vrednosti ovog proteina u serumu. Zato je cilj ove studije bio da se ispita da li je povezanost menopauze i RBP4 nezavisna ili je posredovana insulinskom rezistencijom. Metode: Ukupno 30 žena u premenopauzi i 100 žena u postmenopauzi, koje nisu na terapiji su uključene u studiju preseka. Mereni su antropometrijski i biohemijski parametri, kao i krvni pritisak (KP), HOMA indeksi, procenjena jačina glomerularne filtracije (JGF) i izračunati su. Rezultati: Kod žena u postmenopauzi zabeležene su veće vrednosti RBP4 i nepovoljniji kardiometabolički profil, u poređenju sa ženama u premenopauzi. Višestruka linearnaregresiona analiza je pokazala da su više vrednosti triglicerida (beta=0,315; p=0,002), smanjena JGF (beta=-0,258; p=0,004), više vrednosti sistolnog KP (beta=0,418; p=0,028), i menopauza (beta=0,240; p=0,016), nezavisni prediktori povišenih vrednosti RBP4 u serumu (R2-adjusted=0,310; F=6,522; p lt 0,001). Zaključak: Menopauza utiče na vrednosti RBP4 u serumu, što treba uzeti u obzir prilikom ispitivanja uloge ovog adipokina u pojavi kardiometaboličkih poremećaja.

85th Congress of the European-Atherosclerosis-Society (EAS), 2017.

Aim: Although previous studies confirmed the association between obesity and hypertension, the underlying pathophysiological mechanism is not well elucidated, specially considering the fact that discordant results exist when examining the independent role of obesity and/or insulin resistance on risk for hypertension onset. Therefore, we aimed to examine if obesity [as measured with body mass index (BMI)] is a predictor for hypertension, independently of insulin resistance [as measured with Homeostasis model assessment of insulin resistance (HOMA-IR)] in the cohort of postmenopausal women. Methods: A total of 150 postmenopausal women non-treated with medications(among them 44.7% hypertensive)were included in cross-sectional study. Anthropometric and biochemical parameters, so as blood pressure were obtained. HOMA-IR was calculated. Results: Multivariate logistic regression analysisrevealed that both, BMI and HOMA-IR were the independent predictors of blood pressure in postmenopausal women (OR=1.240, p=0.035 and OR=2.419, p=0.008, respectively). Rise in BMI for 1 kg/m2 enhanced the probability for higher blood pressure by 24%. Also, elevation in HOMA-IR for 1 unit, rose the probability for higher blood pressure almost 2.5 times. Even 47% of variation in blood pressure could be explained with this Model. Also, this Model correctly classified 76% of postmenopausal women having hypertension. Conclusions: Both, obesity and insulin resistance are the independent predictors of blood pressure in postmenopausal women. Cilj: Premda su ranije studije potvrdile vezu između gojaznosti i hipertenzije, patofiziološki mehanizam ove povezanosti još uvek nije rasvetljen, naročito što postoje oprečni rezultati kada je u pitanju nezavisna uloga gojaznosti i/ili insulinske rezistencije u nastanku hipertenzije. Stoga je cilj studije bio da se ispita da li je gojaznost [merena indeksom telesne mase (ITM)] prediktor za nastanak hipertenzije, nezavisno od insulinske rezistencije [merene HOMA indeksom (HOMA-IR)] u kohorti žena u postmenopauzi. Metode: Ukupno 150 žena u postmenopauzi koje nisu na terapiji (među njima 44,7% sa hipertenzijom) su uključene u studiju preseka. Antropometrijski i biohemijski parametri, kao i krvni pritisak su mereni. HOMA-IR je računat. Rezultati: Multivarijantna logistička regresiona analiza je pokazala da su i ITM (OR=1,240; p=0,035) i HOMA-IR (OR=2,419; p=0,008)nezavisni prediktori krvnog pritiska kod žena u postmenopauzi. Povećanje ITMza1 kg/m2 povećava verovatnoću za pojavu hipertenzije za 24%. Takođe, porast HOMA-IR za 1 jedinicu povećava verovatnoću za pojavu hipertenzije za skoro 2,5 puta. Čak 47% varijacije u vrednosti krvnog pritiska može biti objašnjeno ovim modelom. Takođe, ovaj model je ispravno klasifikovao 76% žena u postmenopauzi koje imaju hipertenziju. Zaključak: I gojaznost, i insulinska rezistencija su nezavisni prediktori krvnog pritiska kod žena u postmenopauzi.

Aim: The purpose of this study was to investigate the relationship between anthropometric parameters and serum lipid concentrations in both preadolescent and adolescent girls and boys. Materials & Methods: Basic lipid status parameters were determined in fasting venous blood from 186 preadolescents and adolescents. Atherogenic indices were calculated. Results: Two-way analysis of variance showed significant interactions between age and BMI subgroups in girls at the level of HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C, total cholesterol/HDL-C and LDL-C/HDL-C. Ordinal regression analysis showed that increasing age in both genders reduced the probability of higher HDL-C concentrations. Conclusion: Age was an independent predictor for lower HDL-C concentration in both genders. BMI was the most significant independent predictor for most lipid parameters in girls.

Background: Recent studies hypothesize that dyslipidemia can predict glycated hemoglobin (HbA1c) and could be important contributing factor to the pathogenesis of type 2 diabetes mellitus (DM2). Therefore, we aimed to evaluate the influence of lipid parameters on long-term glycemic control in DM2. Materials and Methods: A total of 275 sedentary DM2 (mean [+/- standard deviation] age 60.6 [+/- 10.0] years) who volunteered to participate in this cross-sectional study were enrolled. Anthropometric (body weight, body hight, and waist circumference), biochemical parameters (fasting glucose, HbA1c, lipid parameters, creatinine), as well as blood pressure were obtained. Results: Total cholesterol (odds ratio [OR] = 1.30, 95% confidence interval [CI] [1.02-1.66], P = 0.032), triglycerides (OR = 1.34, 95% CI (1.07-1.67), P = 0.010), and low density lipoprotein cholesterol (OR = 1.42, 95% CI [1.10-1.83], P = 0.006) were the independent predictors of higher HBA1c, and as they increased by 1 mmol/L each, probabilities of higher HBA1c increased by 30%, 34%, and 42%, respectively. Low level of high-density lipoprotein cholesterol (HDL-c) was found to be the independent predictor of higher HBA1c (OR = 0.44, 95% CI [0.20-0.67], P = 0.039), and increase in HDL-c by 1 mmol/L, reduced the probability of higher HBA1c by 56%. Conclusion: Unfavorable lipid profile can predict HbA1c level in DM2 patients. Early diagnosis of dyslipidemia, as well as its monitoring and maintaining good lipids control can be used as a preventive measure for optimal long-term glycemic control.