Impact of insulin resistance, dyslipidemia, oxidative stress and adipokines on blood pressure and cardiovascular diseases in obese children and adolescents.

Uvod: Gojaznost je postala jedan od najvažnijih globalnih zdravstvenih problema. Globalna epidemija gojaznosti je udružena sa porastom prevalencije arterijske hipertenzije. Sa porastom broja dece sa hipertenzijom, očekuje se porast broja komplikacija hipertenzije u detinjstvu. Najvažnija komplikacija arterijske hipertenzije je hipertrofija miokarda leve komore koja se nalazi u oko 30% dece sa hipertenzijom. Hipertrofija leve komore je poznat faktor rizika za kardiovaskularnu bolest odraslih. Metabolički činioci udruženi sa gojaznošću kao što su insulinska rezistencija, inflamacija i oksidativni stres mogu uticati na kardiovaskularna oštećenja kod dece i adolescenata. Cilj: Cilj rada je ispitati faktore rizika kardiovaskularnih obolenja kod gojazne dece i adolescenata sa i bez hipertenzije. Radi ostvarenja cilja ispitivanja postavljeni su sledeći zadaci istraživanja: ispitivati povezanost parametara oksidativnog stresa i adipokina sa debljinom intime i medije karotidne arterije i sa insulinskom rezistencijom; odrediti prevalenciju hipertrofije miokarda leve komore i poremećene geometrije leve komore; otkriti faktore koji utiču na povećanje indeksa mase leve komore i na poremećenu geometriju leve komore. Metodologija: Studija presek izvedena na Univerzitetskoj dečjoj klinici, uključila je 103 gojazna pacijenta i 30 zdrave normalno uhranjene dece. Gojazni pacijenti su na osnovu rezultata ambulatornog monitoringa krvnog pritiska podeljeni u 2 grupe: gojazne sa i bez hipertenzije. Učinjena su sledeća ispitivanja: odreĎivanje debljine intime i medije karotidnih arterija, ehokardiografija, test opterećenja fizičim naporom, i laboratorijske analize krvi i urina. Laboratorijske analize su uključivale oralni glukoza tolerans test sa insulinom, glikozilirani hemoglobin (HbA1c), serumske elektrolite, ureju, kreatinin, mokraćnu kiselinu, C reaktivni protein, holesterol, trigliceride, lipoproteine velike gustine (HDL-holesterol), lipoproteine male gustine (LDL-holesterol), markere oksidativnog stresa, leptin i adiponektin. Parametri oksidativnog stresa koji su odreĎeni su prooksidativno-antioksidativni balans, uznapredovali produkti oksidacije proteina, malondialdehid, i superoksidni anjon...Introduction: Obesity has become one of the most important global health problems. The global epidemic of obesity is associated with an increase in the prevalence of hypertension. Increase of the number of children with hypertension is expected to increase the number of complications of hypertension in childhood. The most important complication of hypertension is left ventricular hypertrophy which is found in about 30% of children with hypertension. Left ventricular hypertrophy is a known risk factor for cardiovascular disease of adults. Metabolic factors associated with obesity such as insulin resistance, inflammation and oxidative stress may affect the cardiovascular damage in children and adolescents. Aim: to investigate the risk factors of cardiovascular disease in obese children and adolescents with and without hypertension. In order to realize the aim the following tasks were assigned: analyze the relationship of oxidative stress parameters and adipokines with intima-media thickness of the carotid artery (cIMT), and with insulin resistance; determine the prevalence of left ventricular mass and impaired left ventricular geometry; discover the factors affecting the increase in left ventricular mass index, and abnormal left ventricular geometry. Methodology: The cross-sectional study performed at the University Children’s Hospital, included 103 obese patients and 30 healthy nonobese children. Obese patients were divided into 2 groups based on the results of ambulatory monitoring of blood pressure: obese with and without hypertension. We performed the following tests: the determination of the intima and media thickness of the carotid artery, echocardiography, exercize stress test, and laboratory analysis of blood and urine. Laboratory analysis included oral glucose tolerance test with insulin, glycosylated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, uric acid, C-reactive protein, cholesterol, triglycerides, high-density lipoproteins (HDL-cholesterol), low density lipoprotein (LDL-cholesterol), markers of oxidative stress, leptin and adiponectin. Parameters of oxidative stress, which are determined included prooxidant-antioxidant balance, advanced oxidation protein products, malondialdehyde, and superoxide anion..

Pedijatrijski nefrotski sindrom: međusobna interakcija oksidativnog stresa i inflamacije

Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (- SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflam- matory parameters such as pentraxin 3 (PTX3), leptin, programmed cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the dis- ease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (r s =0.42, p=0.027 and r s =0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxi- dant capacity may contribute to nephrotic syndrome devel- opment. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflam- mation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.Uvod: Patofiziološki mehanizmi ključni u razvoju nefrotskog sindroma (NS) u pedijatrijskoj populaciji još uvek nisu u potpunosti razjašnjeni. Ova studija ima za cilj proučavanje sinergističkog delovanja oksidativnog stresa i inflamacije u patogenezi NS. Takođe, jedan od ciljeva ove studije je i ispitivanje veze hipertenzije sa stepenom oksidativnog stresa i inflama - cije kod pacijenata u akutnoj fazi bolesti. Metode: U studiju je uključeno 33 dece sa NS uzrasta od 2 do 9 godina. Uzorci krvi su prikupljeni tokom akutne faze i remisije. Od parametara oksidativnog statusa određivani su: totalni oksidativni status (TOS), uznapredovali proizvodi oksidacije proteina (AOPP), balans prooksidans-antioksidans (PAB), sulfhidrilne grupe (-SH), paraoksonaza 1 (PON1) i ukupan antioksidativni status (TAS) u serumu su mereni spektrofometrijski, a od parametara inflamacije su pentraksin 3 (PTX3), leptin, ligand programirane smrti ćelije 1 (PD-L1) i E-kadherin određivani metodom enzimskog imunosorbentnog testa (ELISA). Rezultati: Pacijenti sa NS i hipertenzijom imali su značajno više nivoe AOPP i TOS (p=0.029 i p=0.003, respektivno). U akutnoj fazi bolesti su uočene nižu aktivnost -SH i PON1 u poređenju sa remisijom (p<0.001, za oba). Nivoi PTX 3 su bili viši, dok su nivoi leptina bili niži tokom akutne faze (p<0.001, za oba). PTX 3 je korelirao sa AOPP i TAS u akutnoj fazi, ali ne i u remisiji (rs=0.42, p=0.027 i rs=0.43, p=0.025,respektivno). U akutnooj fazi utvrđena je negativna korelacija između AOPP i leptina, koja je nestala u remisiji (rs=-0.42, p=0.028). Zaključak: Rezultati ove studije ukazuju da hipertenzija utiče na markere oksidativnog stresa, a smanjeni antioksidativni kapacitet može doprineti razvoju NS. PTX3 se pojavljuje kao potencijalni marker aktivnosti bolesti, što ukazuje na dinamičku vezu između inflamacije i oksidativnog stresa. Leptin može igrati ulogu u oksidativnom stresu u NS

Clinical Application Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as Indicators of Inflammation Persistence and Acute Kidney Injury in Children with Urinary Tract Infection

Background. The aim of this study was to examine the novel renal biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assist pediatricians in the assessment of longer duration of inflammation and acute kidney injury (AKI) development during urinary tract infection (UTI). Methods. The patients enrolled in the study comprised 50 children (mean age was 6 months) with UTI. NGAL in serum and urine (sNGAL and uNGAL, resp.) and KIM-1 in urine were measured by enzyme-linked immunosorbent assays. Results. uNGAL levels in subjects with longer duration of inflammation were higher (115.37 ng/mL) than uNGAL levels in subjects with shorter duration of inflammation (67.87 ng/mL, P = 0.022). Difference in sNGAL and KIM-1 levels was not significant (P = 0.155 and P = 0.198, resp.). Significant difference was seen in KIM-1 excretion among groups with and without AKI (P = 0.038). KIM-1 was not able to discriminate between subjects with and without AKI (area under the curves (AUC) = 0.620, P = 0.175). Conclusions. uNGAL cannot be used for screening of the duration of inflammation during UTI. Accuracy of KIM-1 in screening of AKI development in children with UTI is low. We suggest larger studies to check the negative predictive value of KIM-1 for the development of AKI

Oxidative status parameters in children with urinary tract infection

Introduction: Urinary tract infection (UTI) is one of the most common bacterial infectious diseases in children. The aim of this study was to determine the total prooxidant and antioxidant capacity of children with UTI, as well as changes of oxidative status parameters according to acute inflammation persistence and acute kidney injury (AKI) development. Materials and methods: The patients enrolled in the study comprised 50 Caucasian children (median age was 6 months) with UTI. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), inflammation marker C-reactive protein (CRP) and renal function parameters urea and creatinine were analyzed in patient's serums. Results: According to duration of inflammation during UTI, TAS values were significantly higher (0.99 vs. 0.58 mmol/L, P = 0.017) and OSI values were significantly lower (0.032 vs. 0.041 AU, P = 0.037) in the subjects with longer duration of inflammation than in the subjects with shorter duration of inflammation. We did not find significant difference in basal values of oxidative status parameters according to AKI development. Conclusions: OSI values could detect the simultaneous change of TAS and TOS due to change in the oxidative-antioxidant balance during the recovery of children with UTI. TAS and OSI as markers of oxidative stress during UTI are sensitive to accompanying inflammatory condition. Further investigations are needed to evaluate whether TAS, TOS and OSI could be used to monitor disease severity in children with UTI

Alterations of HDL Particles in Children with End-Stage Renal Disease

Background: Unfavorable lipid profile presents one of most important risk factor for cardiovascular disease in renal pathology. Myeloperoxidase (MPO) as enzyme which oxidizes lipoproteins and paraoxonase1 (PON1) as anti-oxidative enzyme have been involved in pathogenesis of cardiovascular disease. In the present study we sought to assess oxidative stress status, lipoprotein subclasses distribution as well as functionality of high density lipoprotein (HDL) trough MPO/PON1 ratio in children with chronic kidney disease (CKD) and children after renal transplantation. Methods: PON1 activity and oxidative stress parameters were measured spectrophotometrically, while MPO concentration was determined using immunoassay. Separation of lipoprotein subclasses was performed by vertical gradient gel electrophoresis in 19 children with different stage of CKD and 19 post-transplantation patients (PT). Results: CKD patients had increased MPO/PON1 ratio and higher prevalence of smaller HDL subclasses when compared to PT subjects. Also, there was a significant positive correlation between MPO level and MPO/PON1 ratio with relative proportion of smaller HDL subclasses. Conclusions: Children with CKD have impaired HDL distribution that is improved after kidney transplantation. Since that measurement of HDL distribution and functionality arenot routinely available, MPO/PON1 ratio may be useful marker that could provide necessary information

Association of Myeloperoxidase and the Atherogenic Index of Plasma in Children with End-Stage Renal Disease

Background: The aim of this study was to explore oxidative stress status, especially the enzyme myeloperoxidase in children with end-stage renal disease. Also, we investigated possible associations between the atherogenic index of plasma and these parameters. Methods: Lipid status parameters, oxidative stress status parameters, and myeloperoxidase concentration were measured in the sera of 20 children in the last stage of chronic renal disease (ESRD) and 35 healthy children of matching age and sex. The Atherogenic Index of Plasma (AIP) was calculated according to the appropriate equation. Results: We did not find any significant differences in myeloperoxidase concentrations between the investigated groups (p = 0.394). Oxidative stress parameters were, however, significantly higher in the patient group (p lt 0.001), as well as the atherogenic index of plasma (p lt 0.001). Myelo per oxidase concentration and advanced oxidation protein product (AOPP) concentration were independently associated with increased AIP in the patient group (p lt 0.05). Conclusions: Changes in AIP in children with ERSD are associated with the oxidative stress status and myeloper oxidase concentration

Rezistin, inflamacija i dislipidemija kod gojazne dece i adolescenata

Introduction: Childhood obesity is related to cardiovascular diseases and diabetes mellitus type 2 in later life. Resistin, an adipokine primarily secreted by monocytes and tissue macrophages in humans, is considered to be associated with these conditions. The Aim: To examine the correlations between resistin concentration and anthropometric parameters, lipid status, inflammatory markers and parameters of insulin resistance in obese children and adolescents. Material and Methods: The study included 66 patients (40 boys, 26 girls), which underwent anthropometric measuring and laboratory testing (glucose level, total cholesterol, high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), triglycerides, uric acid, high-sensitivity C-reactive protein (hsCRP) and glycosylated hemoglobin (HbA1c). Insulin resistance was estimated with HOMA-IR (homeostasis model assessment of insulin resistance). Results: We determined that 63.3% of our patients had dyslipidemia, while hsCRP and uric acid levels suggested an ongoing inflammation. We established that there was a correlation between resistin concentration and waist to hip ratio (WHR) (r=0.294, p lt 0.05), as well as between resistin concentration and HOMA-IR (r=0.293, p lt 0.05). Also, uric acid levels correlated with obesity parameters. While comparing parameters by gender we found a significant difference in height (p lt 0.01), WHR (p lt 0.001), uric acid levels (p lt 0.01) and HOMA-IR (p lt 0.01). Conclusion: Our results show a link between obesity, inflammation and dyslipidemia in children and adolescents. In the future, resistin could become a significant clinical marker for evaluation of cardiometabolic risk.Uvod: Gojaznost u dečjem uzrastu se povezuje sa razvojem kardiovaskularnih bolesti i tipa 2 dijabetes melitusa u kasnijem dobu. Smatra se da je rezistin, adipokin kojeg u humanom organizumu luče monociti i tkivne makrofage, povezan sa ovim poremećajima. Cilj: Ispitati povezanost koncentracije rezistina kod gojazne dece i adolescenata sa antropometrijskim parametrima gojaznosti, lipidnim statusom, inflamatornim markerima i parametrima insulinske rezistencije. Materijal i metode: U istraživanju je učestvovalo 66 ispitanika (40 dečaka, 26 devojčica) kojima su izvršena antropometrijska merenja i laboratorijska ispitivanja (koncentracije glukoze, ukupnog holesterola, holesterola u česticama lipoproteina visoke gustine (eng. high-density lipoprotein, HDL) i niske gustine (eng. low-density lipoprotein, LDL), triglicerida, mokraćne kiseline, visokoosetljivog C-reaktivnog proteina (high-sensitivity C-reactive protein; hsCRP) i glikoziliranog hemoglobina (HbA1c)). Insulinska rezistencija je procenjena na osnovu modela za izračunavanje indeksa insulinske rezistencije (eng. homeostasis model assessment of insulin resistance; HOMA-IR). Rezultati: Kod 63,3% ispitanika utvrdili smo prisutnu dislipidemiju, a dobijene vrednosti hsCRP i mokraćne kiseline ukazuju na prisustvo inflamacije. Utvrdili smo korelaciju između koncentracije rezistina i odnosa obima struka i kukova (r=0,294, p lt 0,05) i između koncentracije rezistina i HOMA-IR (r=0,293, p lt 0,05). Ustanovili smo povezanost koncentracije mokraćne kiseline i parametara gojaznosti. Upoređivanjem parametara između polova, značajna razlika postoji u telesnoj visini (p lt 0,01), odnosu obima struka i kukova (p lt 0,001), mokraćnoj kiselini (p lt 0,01) i HOMA-IR (p lt 0,01). Zaključak: Naši rezultati ukazuju na povezanost gojaznosti, inflamacije i dislipidemije kod dece i adolescenata. Rezistin bi u budućnosti mogao biti značajan za procenu kardiometaboličkog rizika u ovoj populaciji

Associations of Apgar score and size at birth with lipoprotein subclasses in juvenile obesity

N Background/aim: Juvenile obesity is associated with several metabolic abnormalities, one of them being atherogenic dyslipidemia. Suboptimal fetal growth is associated with obesity risk in childhood, but also with increased rate of metabolic diseases in later life. This study investigated associations of neonatal data (Apgar score, birth weight and birth length) with low-density lipoprotein and high-density lipoprotein (LDL and HDL) subclasses in a group of obese children, as well as a possible impact of breastfeeding duration on obesity-associated lipoprotein subclasses distributions. Materials and methods: We included 42 obese children, aged 14.2 +/- 2.1 years. LDL and HDL subfractions were separated by gradient gel electrophoresis and biochemical parameters were assessed by routine methods. Results: Compared with obese children with Apgar >= 9, the group with Apgar lt 9 had significantly higher percentages of small, dense LDL particles (P lt 0.05), due to reduced LDL I (P lt 0.01) and increased LDL III subclasses (P lt 0.05). Birth weight was positively associated with the proportions of LDL I particles (P lt 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P lt 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P lt 0.01) and lower proportion of HDL 2a particles (P lt 0.05) than their >= 3 months breastfed peers. Conclusion: The results showed significant associations of neonatal characteristics with LDL and HDL particle distributions in obese children. In addition, our results point toward positive aspects of longer breastfeeding duration on lipoprotein particle distributions in obese children

SuO033EXPLORING THE DIFFERENTIAL MORTALITY RISK IN EUROPEAN CHILDREN WITH END-STAGE RENAL DISEASE - RESULTS FROM THE ESPN/ERA-EDTA REGISTRY

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