The association between oxidative stress, inflammation and cardiovascular risk factors in obese postmenopausal women

Uvod: Oksidativni stres i inflamacija, koji postoje kod gojaznih osoba, mogu imati važnu ulogu u nastanku kardiovaskularnih bolesti koje su vodeći uzrok smrtnosti u ovoj populaciji. Međutim, priroda odnosa između gojaznosti, oksidativnog stresa i inflamacije ostaje i dalje otvoreno pitanje. Cilj: Cilj ovog istraživanja je bio da se ispita postojanje razlike u nivou markera inflamacije i parametara oksidativnog stresa kod gojaznih žena u postmenopauzi u odnosu na normalno uhranjene, kao i da se ispita povezanost oksidativnog stresa i inflamacije sa kardiovaskularnim faktorima rizika kod gojaznih žena u postmenopauzi. Metode: U ovom istraživanju izvedena je studija slučajeva i kontrola u koju je bilo uključeno 100 gojaznih žena u postmenopauzi i 50 normalno uhranjenih žena u istom periodu. Svim ispitanicama su izvršena antropometrijska merenja koja su obuhvatila merenje telesne visine, telesne mase i obima struka. Indeks telesne mase je izračunat kao količnik telesne mase izražene u kilogramima i kvadrata telesne visine izražene u metrima (kg/m2). Određivani su sledeći biohemijski parametri: glukoza, insulin, HOMA-IR, lipidni status, pokazatelji bubrežne funkcije, markeri inflamacije, markeri oksidativnog stresa, polni hormone i globulin koji vezuje polne hormone (SHBG). Statistička obrada podataka izvršena je primenom SPSS statističkog programskog paketa. Rezultati: Gojazne ispitanice u postmenopauzi su imale blago povišenu aktivnost superoksid dismutase (SOD) (p>0,05) i značajno veći nivo mokraćne kiseline (p<0,001), kao i značajno nižu aktivnost glutation peroksidaze (GPx) (p<0,05) u odnosu na normalno uhranjene žene. Kod gojaznih žena u postmenopauzi aktivnost GPx je korelirala sa telesnom masom (p<0,05), a izmenjena aktivnost GPx i SOD je korelirala sa nivoom FSH kod ovih žena (p<0,05)...Introduction: Oxidative stress and inflammation reported in obesity may have important role in cardiovascular disease which is the leading cause of death in this population. However, the nature of relation between obesity, oxidative stress, and inflammation is still an open question. Aim: The aim of this study was to examine the difference between inflammation and oxidative stress markers in normal weight and obese postmenopausal women, as well as to investigate the association between oxidative stress, inflammation and cardiovascular risk factors in obese postmenopausal women. Methods: A total of 100 overweight/obese postmenopausal women and 50 age-matched normal weight controls were included in this case-control study. Anthropometric parameters: height, weight and waist circumference (WC) were measured, and body mass index was calculated as weight in kilograms divided by height in meters squared (kg/m2) in all participants. Biochemical parameters: glucose, insulin, HOMA-IR, lipid profile, kidney function markers, inflammation markers, oxidative stress markers, sex hormones, as well as sex-hormone binding globuline level (SHBG). Statistical analysis was performed using SPSS statistical package. Results: Obese postmenopausal women had slightly higher superoxide dismutase (SOD) activity (p>0.05) and higher serum uric acid level (p<0.001), but lower gluthatione peroxide (GPx) activity (p<0.05), as compared with the normal weight postmenopausal women. In obese postmenopausal women GPx positively correlated with body weight (p<0.05), while both GPx and SOD activity correlated positively with FSH (p<0.05). Moreover, anthropometric parameter (WC), and kidney function markers (cystatin C and estimated glomerular filtration rate) were independent predictors of uric acid level (p<0.001) in obese postmenopausal women..

Serum cystatin C levels are associated with triglycerides/high-density lipoprotein cholesterol ratio in adolescent girls ages between 16-19 years old

OBJECTIVE: The pathophysiological role of cystatin C in cardiometabolic disorders is not completely explored in young population. On the other hand, together with the increase in obesity, dyslipidemia and insulin resistance (IR) are often observed even in youngsters. The aim of the study was to investigate the relationship between cystatin C and triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-c), as an indicator of dyslipidemia and a surrogate marker of IR in the cohort of adolescent girls ages between 16-19 years. PATIENTS AND METHODS: A total of 99 girls were included in the study. Anthropometric and biochemical parameters were provided. Associations of biochemical markers with TG/HDL-c ratio were tested using univariable and multivariable ordinal regression analysis for TG/HDL-c ratio tertiles as dependent variable. RESULTS: In univariate analysis, cystatin C levels were significantly associated with TG/HDL-c ratio (OR=1.813; 95% CI: 1.190-2.757, p=0.005). Furthermore, multivariate analysis revealed that cystatin C was an independent predictor of TG/HDL-c ratio when body mass index and high sensitivity C-reactive protein (i.e., markers that were significantly correlated with TG/HDL-c ratio in Spearman’s correlation analysis) were included in the Model. Adjusted odds for cystatin C (OR=1.621; 95% CI: 1.028-2.552, p=0.037) demonstrated that rise in cystatin C by 0.1 mg/L increased the probability for higher TG/HDL-c tertile group by 1.621 times. CONCLUSIONS: Serum cystatin C levels are associated with TG/HDL-c ratio in adolescent girls. Longitudinal studies are needed to confirm the causal relationship between cystatin C and TG/HDL-c ratio and to further explore its diagnostic and therapeutic potential in dyslipidemia and insulin resistance in young population

Editorial: Oxidative stress and inflammation in cardiometabolic disorders

Editorial on the Research Topic: Oxidative stress and inflammation in cardiometabolic disorder

Serum soluble transferrin receptor levels are independently associated with homeostasis model assessment of insulin resistance in adolescent girls

Introduction: Markers 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 methods: A 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. Results: Ferritin, 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. Conclusions: Serum 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

Multimarker Approach as More Reliable Method Than Single Vitamin D in Relationship with Type 2 Diabetes Mellitus in Montenegrin Postmenopausal Women

Objective: Previous studies suggested that ethnic differences, sex and obesity could modify the relationship between 25-hydroxyvitamin D [25(OH)D], glycometabolic markers and/or type 2 di- abetes mellitus (T2D). We aimed to examine the potential relationship between [25(OH)D] and T2D in postmenopausal women in Montenegro. In addition, we aimed to explore if a set of biomarkers, rather than [25(OH)D] as a single biomarker, could better explain its potential association with T2D. Patients and Methods: A total of 116 postmenopausal, otherwise healthy women and 48 postmenopausal women with T2D were included. Univariable and multivariable binary logistic regression analy- sis, along with principal component analysis (PCA), were applied to test the associations between examined biomarkers/set of biomarkers with T2D. Results: Women with T2D had lower serum [25(OH)D] levels than healthy controls (p = 0.024). No independent relationship between [25(OH)D] and T2D was found. PCA extracted three significant factors that were associated with T2D, i.e., age-glycometabolic-related factor (i.e., with positive loadings of age, glucose and insulin; OR = 11.321, p < 0.001), obesity-inflammation- related factor (i.e., with positive loadings of hsCRP and WC, and negative loading of [25(OH)D]; (OR = 2.079, p < 0.001)) and lipid-related factor (i.e., with positive loadings of TG and LDL-c, and negative loading of HDL-c; OR = 1.423, p = 0.044). Conclusions: The relationship between [25(OH)D] and T2D is modulated by central obesity (as measured by WC) and inflammation (as measured with hsCRP) in postmenopausal women. Their joint measurement, rather than [25(OH)D] itself, could provide better information for the risk assessment for T2D in postmenopausal women

Oxidative stress and cardiometabolic biomarkers in patients with non-alcoholic fatty liver disease

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. 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 predictions of oxidative stress and cardiometabolic markers, respectively for NAFLD. Principal component analysis (PCA) was applied to explore its mutual effect on NAFLD status. 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 (p < 0.001) and Pro-oxidants related factor (p < 0.05) for NAFLD status. 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

Total leukocyte count, leukocyte subsets and their indexes in relation to cardiovascular risk in adolescent population

OBJECTIVE: No studies investigated total leukocytes, their subpopulations and novel indexes based on different ratios of leukocyte subsets concerning cardiovascular risk (CV) risk in late adolescents. Therefore, the aim of the present study was to explore such potential relationships. PATIENTS AND METHODS: A total of 156 adolescents were included. CV risk score was calculated by summarizing each risk factor (i.e., female sex, low high density lipoprotein cholesterol (HDL-c), high non-HDL-c, smoking, blood pressure, and fasting glycemia). Adolescents were divided into a low CV risk score (i.e., -2≤ CV risk score ≤1) and moderate/ higher CV risk score (i.e., CV risk score ≥ 2). White blood cell count (WBC) and its subsets were analyzed on an automatic device. The indexes were calculated. RESULTS: Total and differential WBC counts except basophil count were higher in moderate/higher CV risk participants. Multivariate binary regression analysis showed that total WBC count independently increased CV risk score by 1.623 times (p=0.001). Neutrophil and eosinophil counts (p=0.027 and p=0.010, respectively) were independently able to increase CV risk score by 1.486 and 1.556 times, respectively. On the contrary, indexes were not independently correlated with CV risk. CONCLUSIONS: WBC, neutrophil, and eosinophil count are the independent predictors of increased CV risk in adolescents. The associations may indicate the different pathways that lead to CV disease in adulthood

Red cell distribution width is inversely associated with body mass index in late adolescents

OBJECTIVE: There are no studies that investigated the association between red blood cell (RBC) and platelet (PLT) indices in relation to obesity in a cohort of exclusively late adolescents. Hence, we aimed to explore this potential relationship. PATIENTS AND METHODS: A cohort of adolescents (n=156) aged between 16-19 years was included. Iron homeostasis parameters [i.e. RBC, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] and platelet indices [i.e., PLT, mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW)] were determined on the automatic hematology analyzer. Their indexes (i.e., MCV/RBC, MCH/RBC, RDW/MCV, MPV/ PLT and PDW/PCT) were calculated. RESULTS: Univariate binary regression analysis showed negative associations between body mass index (BMI) and RDW, PDW, and PDW/PCT, respectively, and positive associations between BMI and MPV and PCT, respectively. However, only RDW kept the independent negative association with BMI in multivariate binary regression analysis [Odds Ratio (95% Confidence Interval)=0.734 (0.548-0.983); p=0.038]. CONCLUSIONS: Lower RDW values are the independent predictor of higher BMI in the adolescent population. As a low-cost and simply measured parameter, RDW could be a useful diagnostic biomarker in young populations with overweight/obesity

Kardiometabolički rizik u gradske djece u Crnoj Gori - povezanost s pretilošću i spolom

Considering previously reported discrepant results in the literature, we aimed to investigate the impact of gender and overweight/obesity on cardiometabolic risk (CMR) among Montenegrin urban children. The cross-sectional study included random sample of 201 schoolchildren aged 7-12 years (64% of boys) from Podgorica. Children’s nutritional status was determined according to the International Obesity Task Force criteria. CMR was assessed using a sum of z values of the following five indicators: glucose, total cholesterol, inverted value of high-density lipoprotein cholesterol, triglycerides, and hypertension. Higher CMR was found among both overweight and obese boys compared to normal weight boys (p<0.001). The effect size of the difference in CMR between overweight and obese girls and normal weight counterparts was less prominent (p<0.05). Logistic regression analysis revealed that body mass index was independent predictor of high CMR [odds ratio (OR)=1.06; 95% confidence interval (CI)=1.02-1.10); p=0.002]. On the contrary, we found no impact of socioeconomic status, physical activity or sedentary time on CMR in the examined cohort of schoolchildren. In conclusion, both overweight and obesity even among young population are related to higher CMR and this effect is more prominent among boys as compared to girls.Imajući u vidu oprečne podatke iz literature, cilj našega istraživanja je bio ispitati utjecaj spola i pretilosti na kardiometabolički rizik (KMR) kod gradske djece u Crnoj Gori. Studija presjeka je obuhvatila slučajni uzorak od 201 učenika u dobi od 7-12 godina (64% dječaci) iz Podgorice. Nutritivni status djece procijenjen je prema kriterijima International Obesity Task Force. KMR je izračunat kao zbir z vrijednosti dobivenih zbrajanjem 5 parametara: glukoze, ukupnog kolesterola, inverzne koncentracije kolesterola u lipoproteinima visoke gustoće, triglicerida i visokog krvog tlaka. Pretili i debeli dječaci su imali veći KMR u usporedbi s normalno uhranjenim dječacima (p<0,001). Ova razlika u KMR bila je manje izražena kod pretilih i debelih djevojčica (p<0,05) u usporedbi s normalno uhranjenim djevojčicama. Logistička regresija je pokazala da je indeks tjelesne mase nezavisan prediktor povećanog KMR [OR=1,06; (95% CI=1,02-1,10), p=0,002]. Nasuprot tome, nismo utvrdili utjecaj socio-ekonomskog statusa, fizičke aktivnosti ili sedentarnog načina života na povećan KMR u ispitivanoj kohorti djece. U zaključku, postoji povezanost pretilosti i KMR čak i u dječjoj populaciji, ali je taj učinak izraženiji kod dječaka u usporedbi s djevojčicama

Malondialdehid kao nezavisan prediktor indeksa telesne mase kod adolescentkinja

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<0.001) and NOx (p=0.010) concentrations which were significantly higher in overweight/obese adolescent girls. Positive associations were evident between BMI and high sensitivity C-reactive protein (hsCRP) (OR=2.495), BMI and uric acid (OR=1.024) and BMI and MDA (OR=1.062). Multivariable binary regression analysis demonstrated sig- nificant independent associations of BMI and hsCRP (OR=2.150) and BMI and MDA (OR=1.105). Even 76.3% of the variation in BMI could be explained with this Model. Conclusions: Inflammation (as measured with hsCRP) and oxidative stress (as determined with MDA) independently correlated with BMI in teenage girls.Uvod: Imajući u vidu činjenicu da je malo studija koje su ispitivale povezanost oksidativnog stresa i gojaznosti kod adolescenata i da iste pokazuju oprečne rezultate, cilj istraživanja je bio da se ispita povezanost širokog spektra biomarkera nitro-oksidativnog stresa tj. malondialdehida (MDA), ksantin oksidaze (XO), ksantin oksidoreduktaze (XOD), ksantin dehidrogenaze (XDH), produkata uznapredovale oksidacije proteina (AOPP) i produkata azot-monoksida (NOx), kao i enzima antioksidativne zaštite, tj. katalaze (CAT) i gojaznosti u kohorti adolescentkinja starosne dobi izme|u 16 i 19 godina. Metode: Ukupno 59 tinejdžerki je uključeno u ovu studiju preseka. Binarna logistička regresija je primenjena u cilju ispitivanja potencijalne povezanosti između biohemijskih markera i markera nitro-oksidativnog stresa i indeksa telesne mase (ITM). Rezultati: Nije uočena razlika u biomarkerima oksidativnog stresa između normalno uhranjenih i predgojaznih/gojaznih adolescentkinja (odnosno AOPP, XOD, XO, XDH) i CAT, osim u vrednostima MDA (p<0,001) i NOx (p=0,010) koje su bile značajno veće kod predgojaznih/gojaznih adolescentkinja. Pozitivna korelacija je utvrđena izme|u ITM-a i visokosenzitivnog C-reaktivnog proteina (hsCRP) (OR=2,495), ITM-a i mokraćne kiseline (OR=1,024) i ITM-a i MDA (OR=1,062). Multivarijanta binarna regresija je pokazala nezavisnu povezanost ITM-a i hsCRP (OR=2,150), kao i ITM-a i MDA (OR=1,105). Čak 76,3% varijabiliteta ITM-a može biti objašnjeno ovim modelom. Zaključak: Inflamacija (merena hsCRP-om) i oksidativni stres (meren malondialdehidom) nezavisno koreliraju sa ITM kod adolescentkinja