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as well as having predictive value regarding cardiovascular events&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Adipose tissue is a metabolically active organ that produces various bioactive substances&#44; known as adipokines&#44; involved in metabolic&#44; endocrine and immunological processes&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Of these substances&#44; leptin and adiponectin are the most specifically related to adipose tissue&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Leptin is a hormone closely linked to adiposity&#44; and its levels are influenced by the amount of fat mass and adipocyte size&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> It is a non-glycosylated protein encoded by the <span class="elsevierStyleItalic">ob</span> gene&#44; located on chromosome 7&#46; Through its central actions it controls food intake and&#44; indirectly&#44; energy balance&#46; Paradoxically&#44; in obesity&#44; high levels do not suppress appetite&#44; possibly due to a state of leptin resistance&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> It also has pro-inflammatory properties&#44; stimulating the secretion of other cytokines such as interleukin-6 and tumor necrosis factor alpha &#40;TNF-&#945;&#41;&#44; all important in the pathophysiological mechanisms of obesity&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Adiponectin is negatively correlated with obesity&#46; It is the most abundant of the adipokines and is an insulin-sensitizing hormone with anti-inflammatory&#44; anti-atherogenic and anti-diabetic properties&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Synthesis of this hormone is inhibited in situations of cellular hypoxia and oxidative stress&#44; as well as by interleukin-6 and TNF-&#945;&#44; all present in obesity&#46; Its production also appears to be regulated by insulin and inhibited in insulin-resistant states&#44; also common in obesity&#46; Unlike leptin&#44; adiponectin&#39;s levels and anti-inflammatory actions are suppressed in obesity&#44; a consequence of the over-expression of pro-inflammatory molecules&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> particularly in abdominal obesity&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Thus&#44; increased adiposity&#44; especially in the visceral component&#44; results ultimately in an imbalance of adipocyte metabolism that favors the release of pro-inflammatory mediators&#44; contributing to the low-grade inflammatory process that characterizes obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In turn&#44; these mediators affect the actions of other tissues&#44; further stimulating the synthesis of other inflammatory molecules&#44; such as C-reactive protein &#40;CRP&#41;&#44; produced in the liver by the action of interleukin-6&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In obesity&#44; CRP is one of the most important inflammatory markers&#46; In laboratory tests it is quantified by assaying high-sensitivity C-reactive protein &#40;hs-CRP&#41;&#46; CRP is considered an independent cardiovascular risk predictor due to its direct involvement in the various stages of atheroma plaque formation&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In the adult population&#44; relative cardiovascular disease risk can be inferred from its levels&#44; even in apparently healthy individuals&#44; classified as low &#40;&#60;0&#46;1 mg&#47;dl&#41;&#44; moderate &#40;0&#46;1-0&#46;3 mg&#47;dl&#41; or high &#40;&#62;0&#46;3 mg&#47;dl&#41;&#46; Those with hs-CRP above 0&#46;3 mg&#47;dl have twice the risk of acquiring atherosclerotic disease compared to those with low levels &#40;class IIa recommendation&#44; level of evidence B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> In obese children&#44; raised hs-CRP levels suggest a persistent inflammatory process&#44; and&#44; as with the adult population&#44; also confer cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The inflammatory cascade induced by adiposity leads to endothelial dysfunction&#44; which in this patient group raises their cardiovascular risk&#46; Implicitly&#44; nitric oxide bioavailability is compromised&#44; as is vessels&#8217; vasodilatory capacity&#46; Endothelial dysfunction is considered the earliest step in the atherosclerotic process and precedes any morphological vessel wall changes&#46; If the inflammatory milieu is maintained&#44; the arterial wall phenotype undergoes progressive changes that culminate in the formation of the atheromatous plaque&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> Various studies have shown that atherosclerotic disease begins in childhood&#44; mostly in children with cardiovascular risk factors&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and thus obesity is an important predictor of morbidity and mortality in adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">We carried out an observational&#44; cross-sectional analysis in a cohort of obese children recruited from the Cardiovascular Risk Clinic of the Department of Pediatric Cardiology of Coimbra Pediatric Hospital&#44; Portugal&#44; over the course of 2012 and 2013&#46; All parents gave their informed consent for the children to participate in the study&#44; which had been approved by the local Ethics Committee&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The inclusion criteria for the study group were children with primary obesity &#40;BMI above the 95th percentile for gender and age&#41; aged 6-17 years without recent or chronic illness&#46; The control group included healthy children within the same age range with a normal BMI &#40;P5-85&#41;&#46; All children had undergone a 12-hour fast prior to clinical assessment and blood sampling&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The study group included 120 obese children and the control group 41 children&#44; of both sexes&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Weight &#40;in kg to the nearest 100 g&#41; was determined using a SECA 220 digital weight scale &#40;Seca Medical Scales and Measuring Systems&#44; Germany&#41; and standing height &#40;in cm to the nearest 0&#46;1 cm&#41; was determined using a stadiometer incorporated in the same apparatus&#44; with the children wearing only underwear&#46; BMI was calculated based on the formula&#58; weight &#40;kg&#41;&#47;height &#40;cm&#41;<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> We used the World Health Organization BMI percentile charts to define BMI &#40;obesity if BMI &#62;P95&#59; normal if BMI P5-P85&#41;&#46; WC&#44; to the nearest 0&#46;1 cm&#44; was measured using a flexible plastic tape placed midway between the last rib and the iliac crest and plotted on published WC charts&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Body fat mass percentage &#40;FM&#37;&#41; was determined by bioelectric impedance using a BIA 101 Anniversary device &#40;Akern Srl&#44; Italy&#41;&#46; FM&#37; was defined according to the charts published by McCarthy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Blood collection and biochemical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Fasting venous blood samples &#40;15 ml&#41; were obtained to determine hematological parameters&#46; Blood specimens were collected in vacutainer tubes with or without ethylenediaminetetraacetic acid&#46; Serum and plasma were prepared and then frozen at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C for storage until analysis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">hs-CRP was determined by immunonephelometry from serum samples and processed in a BN ProSpec<span class="elsevierStyleSup">&#174;</span> system &#40;Siemens Healthcare Diagnostics Inc&#46;&#41; &#40;undetected if &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02 mg&#47;dl&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Quantitative measurements of serum leptin and adiponectin levels were performed using commercially available enzyme-linked immunosorbent assay kits &#40;eBioscience&#44; San Diego&#44; CA&#44; USA and BioVendor&#44; Brno&#44; Czech Republic&#44; respectively&#41;&#44; and absorbances were measured at 450 nm &#40;Bio-RAD microplate reader model 680&#44; Hercules&#44; CA&#44; USA&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The data were analyzed using SPSS version 20&#46; Descriptive analysis of the parametric variables was performed by calculating the mean and standard error of the mean&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Differences in the demographic and hematological characteristics of the case and control groups were analyzed using the Student&#39;s t test and the Mann-Whitney U test&#44; depending on population distribution&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">For categorical variables&#44; differences between the two groups were assessed using the chi-square test&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Logistic regression was used when clinical variables were controlled between the two groups&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Pearson&#39;s and Spearman&#39;s correlation were used to establish correlations between the parameters in the obese group&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Results were considered statistically significant at p&#60;0&#46;05&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0110" class="elsevierStylePara elsevierViewall">One hundred and twenty obese children&#44; 61 boys and 59 girls&#44; aged between 6 and 17 years &#40;mean 11&#46;65&#177;2&#46;96 years&#41;&#44; were included in the study&#46; The control group was made up of 41 healthy&#44; non-obese children&#44; 29 boys and 12 girls&#44; within the same age group &#40;mean 12&#46;73&#177;2&#46;77 years&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">We firstly compared the two groups&#8217; anthropometric&#44; clinical and laboratory parameters&#44; which showed significant differences for all the variables analyzed &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; With the exception of adiponectin&#44; all were higher in the obese group&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">As both age &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038&#41; and gender &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#41; were also significantly different between the groups&#44; we used logistic regression to adjust for these parameters and repeated the analysis&#44; which demonstrated that adiponectin &#40;p&#60;0&#46;001&#41;&#44; leptin &#40;p&#60;0&#46;001&#41; and hs-CRP &#40;p&#60;0&#46;001&#41; still showed statistically significant differences&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">We then analyzed these parameters as a function of gender and pubertal age&#44; and the statistical differences remained&#44; as can be seen in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">We further aimed to determine correlations between hs-CRP and the other variables&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">hs-CRP was directly and moderately correlated with BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;507&#59; p&#60;0&#46;001&#41;&#44; WC &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;496&#59; p&#60;0&#46;001&#41;&#44; FM&#37; &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;535&#59; p&#60;0&#46;001&#41; and leptin &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;568&#59; p&#60;0&#46;001&#41;&#44; and inversely but weakly correlated with adiponectin &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;240&#59; p&#61;0&#46;007&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The same analysis within the obese group showed that hs-CRP maintained a direct but weak correlation with BMI&#44; WC&#44; FM&#37; and leptin&#44; as demonstrated in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; In boys within the obese group&#44; hs-CRP was directly related to WC &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;274&#59; p&#60;0&#46;001&#41;&#44; FM&#37; &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;285&#59; p&#61;0&#46;029&#41; and leptin &#40;r&#61;0&#46;469&#59; p&#60;0&#46;001&#41;&#46; In girls&#44; only leptin was related to hs-CRP &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;353&#59; p&#61;0&#46;006&#41;&#46; In obese pre-adolescents hs-CRP was related to leptin &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;462&#59; &#60;0&#46;001&#41;&#44; whereas in the adolescent obese group it was related to BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;386&#59; p&#61;0&#46;002&#41;&#44; WC &#40;r&#61;0&#46;351&#59; p&#61;0&#46;006&#41;&#44; FM&#37; &#40;r&#61;0&#46;261&#59; p&#61;0&#46;036&#41; and leptin &#40;r&#61;0&#46;462&#59; p&#60;0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">In the obese group&#44; apart from hs-CRP&#44; leptin was directly related to BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;395&#59; p&#60;0&#46;001&#41;&#44; WC &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;390&#59; p&#60;0&#46;001&#41; and FM&#37; &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;378&#59; p&#60;0&#46;001&#41;&#46; Adiponectin was inversely but weakly correlated with BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>-0&#46;276&#59; p&#61;0&#46;002&#41; and WC &#40;r&#61;0&#46;291&#59; p&#61;0&#46;005&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0150" class="elsevierStylePara elsevierViewall">We have demonstrated that in our young obese population there is a correlation between markers of adiposity and leptin&#44; adiponectin and hs-CRP&#44; all important risk factors in the pathogenesis of cardiovascular disease and insulin resistance&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Obesity is a chronic inflammatory disorder&#44; in which leptin&#44; adiponectin and CRP play an important role&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Besides its relationship with energy balance&#44; leptin is also an important immune modulator&#46; Leptin is a member of the cytokine family and shares structural similarities with molecules such as interleukin-6&#44; and is thus considered a pro-inflammatory cytokine&#46; A leptin receptor is expressed in immune cells&#44; and leptin thereby actively influences the functions of T-lymphocytes&#44; natural killer cells&#44; macrophages and monocytes&#46; It also influences the release of inflammatory markers&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> particularly CRP&#44; in turn a major player in cardiovascular disease through its pro-inflammatory actions&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Based on these facts&#44; we sought to establish the relationship between these parameters in a population of Portuguese children with primary obesity&#46; To the best of our knowledge this is the first report relating these parameters in our pediatric obese population&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">We firstly compared the obese group with a control group made up of healthy non-obese children&#44; and found significant differences in leptin &#40;p&#60;0&#46;001&#41;&#44; adiponectin &#40;p&#60;0&#46;001&#41; and hs-CRP &#40;p&#60;0&#46;001&#41; levels between these two groups&#58; in the obese group&#44; leptin and hs-CRP levels were higher&#44; whereas adiponectin levels were lower&#46; These differences are expected&#44; but especially in the obese group&#44; highlight the pathophysiological processes triggered by adiposity present in children as young as six years of age&#44; as clearly shown in our analysis&#46; Age &#40;p&#60;0&#46;038&#41; and gender &#40;p&#60;0&#46;027&#41; were also significantly different&#44; and as such could also account for these differences&#44; but when our sample was adjusted by logistic regression for gender and age&#44; all three variables still remained significantly different&#44; retaining the same pattern&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Leptin reflects fat mass&#59; its levels are influenced by gender and age&#44; particularly at puberty when girls acquire more fat mass&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Previous studies have shown that in non-obese children leptin levels increase in both boys and girls until puberty&#44; at which point they increase in girls and decrease in boys&#44; most likely due to the effects of testosterone&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Not surprisingly&#44; in the obese group&#44; we found leptin to be significantly correlated with BMI&#44; WC&#44; and fat mass percentage&#44; particularly in girls&#44; showing strong gender dimorphism&#44; as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> More importantly&#44; it was also equally and moderately related to hs-CRP&#46; We further aimed to clarify the correlations between hs-CRP&#44; leptin&#44; BMI&#44; WC&#44; fat mass percentage and adiponectin&#46; With the exception of adiponectin&#44; which was inversely but directly related to hs-CRP&#44; all others were directly and moderately correlated with hs-CRP&#46; These trends highlight the role of adiposity and leptin as pro-inflammatory triggers in obesity&#44; and these were evident from our study&#44; regardless of age or pubertal status&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Evidence in animal studies suggests that leptin&#44; like interleukin-6&#44; is capable of directly stimulating the production of hepatic CRP&#44; thus maintaining a low-grade inflammatory state&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> It also appears to compromise nitric oxide bioavailability&#44; and hence contribute towards endothelial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In our study&#44; leptin was the best predictor of hs-CRP levels&#46; This observation may provide a clue to the link between adipocyte dysfunction&#44; inflammation and ultimately endothelial dysfunction&#46; In contrast to our findings&#44; some authors have found that the best predictor of CRP is BMI&#44; while for others it was adiposity&#44;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#8211;39</span></a> but in these studies leptin was not included as a variable&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">As expected&#44; adiponectin showed gender dimorphism and was age-related&#44; being higher in girls than boys&#44; and decreased with age&#46; Our findings showed that&#44; in the obese group&#44; it was inversely correlated with BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>-0&#46;212&#59; p&#61;0&#46;39&#41; and WC &#40;r&#61;-0&#46;278&#59; p&#61;0&#46;06&#41;&#44; but not correlated with hs-CRP or leptin&#46; In a study by Caprio et al&#46;&#44; an association was demonstrated between adiponectin levels and CRP&#44; whereas in ours&#44; as shown&#44; this was not the case&#46; In healthy individuals adiponectin has anti-atherogenic properties and studies have shown that&#44; in adults&#44; hypoadiponectinemia correlates with coronary lesions and is an independent risk factor for the progression of type 2 diabetes&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;41</span></a> In the light of our results&#44; we can infer that the presumptive loss of adiponectin&#39;s protective properties is yet another cardiovascular risk factor present in our population&#44; and if not abated may contribute to early onset cardiovascular disease and type 2 diabetes in this population&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">This study&#39;s main limitation relates to the sample size&#44; particularly the control group&#46; It also only includes a Caucasian population&#44; race thus being a possible source of bias in this study&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Based on our findings&#44; these markers may be considered for use in clinical practice for cardiovascular risk stratification in obese children&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical disclosures</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Protection of human and animal subjects</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Confidentiality of data</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Right to privacy and informed consent</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pediatric obesity is increasingly prevalent in the Portuguese population&#46; Adipocyte dysfunction results in the expression of pro-inflammatory mediators that are responsible for the low-grade inflammatory process that characterizes obesity&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to investigate the relationship between markers of adiposity&#44; inflammation and adipokines in a Portuguese obese pediatric population&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">One hundred and twenty children of both sexes&#44; aged 6&#8211;17 years&#44; were included in this study&#46; The control group consisted of 41 healthy normal-weight children&#46; The variables analyzed were age&#44; gender&#44; body mass index&#44; waist circumference&#44; fat mass percentage&#44; high-sensitivity C-reactive protein &#40;hs-CRP&#41;&#44; leptin and adiponectin&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There were significant differences between controls and obese children for all parameters analyzed&#46; In the obese group&#44; after controlling for age and gender&#44; hs-CRP &#40;p&#61;0&#46;041&#41;&#44; adiponectin &#40;p&#61;0&#46;019&#41; and leptin &#40;p&#60;0&#46;001&#41; still showed significant statistical differences&#46; A direct correlation was found between hs-CRP&#44; leptin&#44; body mass index and waist circumference&#44; the strongest being with leptin &#40;r&#61;0&#46;568&#59; p&#60;0&#46;001&#41;&#46; This trend remained statistically significant&#44; regardless of gender or pubertal age&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Considering the role of leptin&#44; adiponectin and hs-CRP in the genesis of endothelial dysfunction&#44; they may be used in clinical practice for risk stratification&#44; as well as in the assessment of weight control programs&#46;</p>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A obesidade pedi&#225;trica &#233; prevalente na nossa popula&#231;&#227;o&#46; A adiposidade resulta na express&#227;o de marcadores pr&#243;-inflamat&#243;rios que s&#227;o respons&#225;veis pelo processo de inflama&#231;&#227;o de baixo grau que caracteriza a obesidade&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Tivemos como objetivo avaliar a rela&#231;&#227;o entre marcadores de adiposidade&#44; inflama&#231;&#227;o e adipocinas num grupo de crian&#231;as portuguesas obesas&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;das no estudo 120 crian&#231;as obesas&#44; entre os 6 e 17 anos de idade&#46; O grupo controlo continha 41 crian&#231;as saud&#225;veis&#44; sem excesso de peso&#44; dentro da mesma faixa et&#225;ria&#46; As vari&#225;veis analisadas foram&#58; idade&#44; g&#233;nero&#44; &#237;ndice de massa corporal&#44; circunfer&#234;ncia abdominal&#44; percentagem de massa gorda&#44; prote&#237;na C-reativa ultra-sens&#237;vel&#44; leptina e adiponectina&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Todos os par&#226;metros analisados encontravam-se significativamente mais elevados no grupo de crian&#231;as obesas&#46; No grupo obeso&#44; ap&#243;s avalia&#231;&#227;o por regress&#227;o log&#237;stica&#44; ajustando &#224; idade e g&#233;nero&#44; a prote&#237;na C-reativa ultra-sens&#237;vel &#40;p&#61;0&#44;041&#41;&#44; adiponectina &#40;p&#61;0&#44;019&#41; e leptina &#40;p&#60;0&#44;001&#41;&#44; mantiveram significado estat&#237;stico&#46; Os marcadores de adiposidade correlacionaram-se diretamente com a leptina &#40;p&#61;0&#44;001&#41; e inversamente com a adiponectina &#40;p&#61;0&#44;029&#41;&#46; Encontr&#225;mos tamb&#233;m uma correla&#231;&#227;o direta entre a prote&#237;na C-reactiva ultra-sens&#237;vel&#44; leptina&#44; &#237;ndice de massa corporal e circunfer&#234;ncia abdominal&#44; sendo a correla&#231;&#227;o mais robusta com a leptina &#40;&#961;&#61;0&#44;568&#59; p&#60;0&#44;001&#41;&#46; Esta tend&#234;ncia manteve-se independentemente do g&#233;nero ou idade puberal&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#245;es</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Considerando a rela&#231;&#227;o da leptina&#44; adiponectina e prote&#237;na C-reativa na g&#233;nese da disfun&#231;&#227;o endotelial&#44; estes poder&#227;o ser &#250;teis na pr&#225;tica di&#225;ria para estratifica&#231;&#227;o de risco&#44; assim como&#44; para avaliar medidas implementadas nos programas para redu&#231;&#227;o de peso em crian&#231;as obesas&#46;</p>"
      ]
    ]
    "nomenclatura" => array:1 [
      0 => array:3 [
        "identificador" => "nom0005"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0075">Abbreviations</span>"
        "listaDefinicion" => array:1 [
          0 => array:1 [
            "definicion" => array:5 [
              0 => array:2 [
                "termino" => "BMI"
                "descripcion" => "<p id="par0220" class="elsevierStylePara elsevierViewall">body mass index</p>"
              ]
              1 => array:2 [
                "termino" => "FM&#37;"
                "descripcion" => "<p id="par0225" class="elsevierStylePara elsevierViewall">fat mass percentage</p>"
              ]
              2 => array:2 [
                "termino" => "hs-CRP"
                "descripcion" => "<p id="par0235" class="elsevierStylePara elsevierViewall">high-sensitivity C-reactive protein</p>"
              ]
              3 => array:2 [
                "termino" => "TNF-&#945;"
                "descripcion" => "<p id="par0240" class="elsevierStylePara elsevierViewall">tumor necrosis factor alpha</p>"
              ]
              4 => array:2 [
                "termino" => "WC"
                "descripcion" => "<p id="par0245" class="elsevierStylePara elsevierViewall">waist circumference</p>"
              ]
            ]
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; FM&#37;&#58; fat mass percentage&#59; WC&#58; waist circumference&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as means &#177; standard error of the mean &#40;SEM&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
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                  \t\t\t\t">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Obese</td><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Mean &#177; SEM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Mean &#177; SEM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&#46;65&#177;0&#46;432&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">12&#46;73&#177;0&#46;270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;038<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">28&#46;465&#177;0&#46;438&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&#46;933&#177;0&#46;429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">WC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">93&#46;15&#177;1&#46;197&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#46;16&#177;0&#46;861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FM&#37; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">36&#46;840&#177;0&#46;647&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;544&#177;0&#46;526&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leptin &#40;ng&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#46;973&#177;1&#46;627&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;845&#177;0&#46;706&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adiponectin &#40;&#956;g&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;597&#177;0&#46;140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;173&#177;0&#46;413&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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Original Article
Pro-inflammatory triggers in childhood obesity: Correlation between leptin, adiponectin and high-sensitivity C-reactive protein in a group of obese Portuguese children
Fatores pró-inflamatórios na obesidade infantil: correlação entre a leptina, adiponectina e proteína C-reativa num grupo de crianças portuguesas obesas
António Piresa,
Autor para correspondência
pires1961@gmail.com

Corresponding author.
, Paula Martinsa, Ana Margarida Pereirab, Joana Marinhoa, Patrícia Vaz Silvaa, Margarida Marquesc, Eduardo Castelaa, Cristina Senab, Raquel Seiçab
a Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal
b Laboratório de Fisiologia, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
c Laboratório de Estatística, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
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obesity is defined by a body mass index &#40;BMI&#41; above the 95th percentile for age and gender&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However&#44; various studies have shown that body fat distribution&#44; particularly visceral fat&#44; rather than BMI&#44; is linked to cardiovascular events&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> About 85&#37; of adipose tissue is subcutaneous&#44; the remainder being located in the abdominal cavity&#44; both intra- and retroperitoneally&#44; and this relationship is maintained regardless of the individual&#39;s weight&#46; Magnetic resonance imaging and computed axial tomography are the gold standard references used to quantify visceral fat&#46; However&#44; in clinical practice&#44; access to these exams is limited&#44; and hence waist circumference &#40;WC&#41; is used to infer visceral fat&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> with which it is strongly correlated&#44; as well as having predictive value regarding cardiovascular events&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Adipose tissue is a metabolically active organ that produces various bioactive substances&#44; known as adipokines&#44; involved in metabolic&#44; endocrine and immunological processes&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Of these substances&#44; leptin and adiponectin are the most specifically related to adipose tissue&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Leptin is a hormone closely linked to adiposity&#44; and its levels are influenced by the amount of fat mass and adipocyte size&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> It is a non-glycosylated protein encoded by the <span class="elsevierStyleItalic">ob</span> gene&#44; located on chromosome 7&#46; Through its central actions it controls food intake and&#44; indirectly&#44; energy balance&#46; Paradoxically&#44; in obesity&#44; high levels do not suppress appetite&#44; possibly due to a state of leptin resistance&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> It also has pro-inflammatory properties&#44; stimulating the secretion of other cytokines such as interleukin-6 and tumor necrosis factor alpha &#40;TNF-&#945;&#41;&#44; all important in the pathophysiological mechanisms of obesity&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Adiponectin is negatively correlated with obesity&#46; It is the most abundant of the adipokines and is an insulin-sensitizing hormone with anti-inflammatory&#44; anti-atherogenic and anti-diabetic properties&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Synthesis of this hormone is inhibited in situations of cellular hypoxia and oxidative stress&#44; as well as by interleukin-6 and TNF-&#945;&#44; all present in obesity&#46; Its production also appears to be regulated by insulin and inhibited in insulin-resistant states&#44; also common in obesity&#46; Unlike leptin&#44; adiponectin&#39;s levels and anti-inflammatory actions are suppressed in obesity&#44; a consequence of the over-expression of pro-inflammatory molecules&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> particularly in abdominal obesity&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Thus&#44; increased adiposity&#44; especially in the visceral component&#44; results ultimately in an imbalance of adipocyte metabolism that favors the release of pro-inflammatory mediators&#44; contributing to the low-grade inflammatory process that characterizes obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In turn&#44; these mediators affect the actions of other tissues&#44; further stimulating the synthesis of other inflammatory molecules&#44; such as C-reactive protein &#40;CRP&#41;&#44; produced in the liver by the action of interleukin-6&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In obesity&#44; CRP is one of the most important inflammatory markers&#46; In laboratory tests it is quantified by assaying high-sensitivity C-reactive protein &#40;hs-CRP&#41;&#46; CRP is considered an independent cardiovascular risk predictor due to its direct involvement in the various stages of atheroma plaque formation&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In the adult population&#44; relative cardiovascular disease risk can be inferred from its levels&#44; even in apparently healthy individuals&#44; classified as low &#40;&#60;0&#46;1 mg&#47;dl&#41;&#44; moderate &#40;0&#46;1-0&#46;3 mg&#47;dl&#41; or high &#40;&#62;0&#46;3 mg&#47;dl&#41;&#46; Those with hs-CRP above 0&#46;3 mg&#47;dl have twice the risk of acquiring atherosclerotic disease compared to those with low levels &#40;class IIa recommendation&#44; level of evidence B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> In obese children&#44; raised hs-CRP levels suggest a persistent inflammatory process&#44; and&#44; as with the adult population&#44; also confer cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The inflammatory cascade induced by adiposity leads to endothelial dysfunction&#44; which in this patient group raises their cardiovascular risk&#46; Implicitly&#44; nitric oxide bioavailability is compromised&#44; as is vessels&#8217; vasodilatory capacity&#46; Endothelial dysfunction is considered the earliest step in the atherosclerotic process and precedes any morphological vessel wall changes&#46; If the inflammatory milieu is maintained&#44; the arterial wall phenotype undergoes progressive changes that culminate in the formation of the atheromatous plaque&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> Various studies have shown that atherosclerotic disease begins in childhood&#44; mostly in children with cardiovascular risk factors&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and thus obesity is an important predictor of morbidity and mortality in adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">We carried out an observational&#44; cross-sectional analysis in a cohort of obese children recruited from the Cardiovascular Risk Clinic of the Department of Pediatric Cardiology of Coimbra Pediatric Hospital&#44; Portugal&#44; over the course of 2012 and 2013&#46; All parents gave their informed consent for the children to participate in the study&#44; which had been approved by the local Ethics Committee&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The inclusion criteria for the study group were children with primary obesity &#40;BMI above the 95th percentile for gender and age&#41; aged 6-17 years without recent or chronic illness&#46; The control group included healthy children within the same age range with a normal BMI &#40;P5-85&#41;&#46; All children had undergone a 12-hour fast prior to clinical assessment and blood sampling&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The study group included 120 obese children and the control group 41 children&#44; of both sexes&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Weight &#40;in kg to the nearest 100 g&#41; was determined using a SECA 220 digital weight scale &#40;Seca Medical Scales and Measuring Systems&#44; Germany&#41; and standing height &#40;in cm to the nearest 0&#46;1 cm&#41; was determined using a stadiometer incorporated in the same apparatus&#44; with the children wearing only underwear&#46; BMI was calculated based on the formula&#58; weight &#40;kg&#41;&#47;height &#40;cm&#41;<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> We used the World Health Organization BMI percentile charts to define BMI &#40;obesity if BMI &#62;P95&#59; normal if BMI P5-P85&#41;&#46; WC&#44; to the nearest 0&#46;1 cm&#44; was measured using a flexible plastic tape placed midway between the last rib and the iliac crest and plotted on published WC charts&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Body fat mass percentage &#40;FM&#37;&#41; was determined by bioelectric impedance using a BIA 101 Anniversary device &#40;Akern Srl&#44; Italy&#41;&#46; FM&#37; was defined according to the charts published by McCarthy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Blood collection and biochemical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Fasting venous blood samples &#40;15 ml&#41; were obtained to determine hematological parameters&#46; Blood specimens were collected in vacutainer tubes with or without ethylenediaminetetraacetic acid&#46; Serum and plasma were prepared and then frozen at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C for storage until analysis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">hs-CRP was determined by immunonephelometry from serum samples and processed in a BN ProSpec<span class="elsevierStyleSup">&#174;</span> system &#40;Siemens Healthcare Diagnostics Inc&#46;&#41; &#40;undetected if &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02 mg&#47;dl&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Quantitative measurements of serum leptin and adiponectin levels were performed using commercially available enzyme-linked immunosorbent assay kits &#40;eBioscience&#44; San Diego&#44; CA&#44; USA and BioVendor&#44; Brno&#44; Czech Republic&#44; respectively&#41;&#44; and absorbances were measured at 450 nm &#40;Bio-RAD microplate reader model 680&#44; Hercules&#44; CA&#44; USA&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The data were analyzed using SPSS version 20&#46; Descriptive analysis of the parametric variables was performed by calculating the mean and standard error of the mean&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Differences in the demographic and hematological characteristics of the case and control groups were analyzed using the Student&#39;s t test and the Mann-Whitney U test&#44; depending on population distribution&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">For categorical variables&#44; differences between the two groups were assessed using the chi-square test&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Logistic regression was used when clinical variables were controlled between the two groups&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Pearson&#39;s and Spearman&#39;s correlation were used to establish correlations between the parameters in the obese group&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Results were considered statistically significant at p&#60;0&#46;05&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0110" class="elsevierStylePara elsevierViewall">One hundred and twenty obese children&#44; 61 boys and 59 girls&#44; aged between 6 and 17 years &#40;mean 11&#46;65&#177;2&#46;96 years&#41;&#44; were included in the study&#46; The control group was made up of 41 healthy&#44; non-obese children&#44; 29 boys and 12 girls&#44; within the same age group &#40;mean 12&#46;73&#177;2&#46;77 years&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">We firstly compared the two groups&#8217; anthropometric&#44; clinical and laboratory parameters&#44; which showed significant differences for all the variables analyzed &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; With the exception of adiponectin&#44; all were higher in the obese group&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">As both age &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038&#41; and gender &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;027&#41; were also significantly different between the groups&#44; we used logistic regression to adjust for these parameters and repeated the analysis&#44; which demonstrated that adiponectin &#40;p&#60;0&#46;001&#41;&#44; leptin &#40;p&#60;0&#46;001&#41; and hs-CRP &#40;p&#60;0&#46;001&#41; still showed statistically significant differences&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">We then analyzed these parameters as a function of gender and pubertal age&#44; and the statistical differences remained&#44; as can be seen in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">We further aimed to determine correlations between hs-CRP and the other variables&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">hs-CRP was directly and moderately correlated with BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;507&#59; p&#60;0&#46;001&#41;&#44; WC &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;496&#59; p&#60;0&#46;001&#41;&#44; FM&#37; &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;535&#59; p&#60;0&#46;001&#41; and leptin &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;568&#59; p&#60;0&#46;001&#41;&#44; and inversely but weakly correlated with adiponectin &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;240&#59; p&#61;0&#46;007&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The same analysis within the obese group showed that hs-CRP maintained a direct but weak correlation with BMI&#44; WC&#44; FM&#37; and leptin&#44; as demonstrated in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; In boys within the obese group&#44; hs-CRP was directly related to WC &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;274&#59; p&#60;0&#46;001&#41;&#44; FM&#37; &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;285&#59; p&#61;0&#46;029&#41; and leptin &#40;r&#61;0&#46;469&#59; p&#60;0&#46;001&#41;&#46; In girls&#44; only leptin was related to hs-CRP &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;353&#59; p&#61;0&#46;006&#41;&#46; In obese pre-adolescents hs-CRP was related to leptin &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;462&#59; &#60;0&#46;001&#41;&#44; whereas in the adolescent obese group it was related to BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;386&#59; p&#61;0&#46;002&#41;&#44; WC &#40;r&#61;0&#46;351&#59; p&#61;0&#46;006&#41;&#44; FM&#37; &#40;r&#61;0&#46;261&#59; p&#61;0&#46;036&#41; and leptin &#40;r&#61;0&#46;462&#59; p&#60;0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">In the obese group&#44; apart from hs-CRP&#44; leptin was directly related to BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;395&#59; p&#60;0&#46;001&#41;&#44; WC &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;390&#59; p&#60;0&#46;001&#41; and FM&#37; &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;378&#59; p&#60;0&#46;001&#41;&#46; Adiponectin was inversely but weakly correlated with BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>-0&#46;276&#59; p&#61;0&#46;002&#41; and WC &#40;r&#61;0&#46;291&#59; p&#61;0&#46;005&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0150" class="elsevierStylePara elsevierViewall">We have demonstrated that in our young obese population there is a correlation between markers of adiposity and leptin&#44; adiponectin and hs-CRP&#44; all important risk factors in the pathogenesis of cardiovascular disease and insulin resistance&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Obesity is a chronic inflammatory disorder&#44; in which leptin&#44; adiponectin and CRP play an important role&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Besides its relationship with energy balance&#44; leptin is also an important immune modulator&#46; Leptin is a member of the cytokine family and shares structural similarities with molecules such as interleukin-6&#44; and is thus considered a pro-inflammatory cytokine&#46; A leptin receptor is expressed in immune cells&#44; and leptin thereby actively influences the functions of T-lymphocytes&#44; natural killer cells&#44; macrophages and monocytes&#46; It also influences the release of inflammatory markers&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> particularly CRP&#44; in turn a major player in cardiovascular disease through its pro-inflammatory actions&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Based on these facts&#44; we sought to establish the relationship between these parameters in a population of Portuguese children with primary obesity&#46; To the best of our knowledge this is the first report relating these parameters in our pediatric obese population&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">We firstly compared the obese group with a control group made up of healthy non-obese children&#44; and found significant differences in leptin &#40;p&#60;0&#46;001&#41;&#44; adiponectin &#40;p&#60;0&#46;001&#41; and hs-CRP &#40;p&#60;0&#46;001&#41; levels between these two groups&#58; in the obese group&#44; leptin and hs-CRP levels were higher&#44; whereas adiponectin levels were lower&#46; These differences are expected&#44; but especially in the obese group&#44; highlight the pathophysiological processes triggered by adiposity present in children as young as six years of age&#44; as clearly shown in our analysis&#46; Age &#40;p&#60;0&#46;038&#41; and gender &#40;p&#60;0&#46;027&#41; were also significantly different&#44; and as such could also account for these differences&#44; but when our sample was adjusted by logistic regression for gender and age&#44; all three variables still remained significantly different&#44; retaining the same pattern&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Leptin reflects fat mass&#59; its levels are influenced by gender and age&#44; particularly at puberty when girls acquire more fat mass&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Previous studies have shown that in non-obese children leptin levels increase in both boys and girls until puberty&#44; at which point they increase in girls and decrease in boys&#44; most likely due to the effects of testosterone&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Not surprisingly&#44; in the obese group&#44; we found leptin to be significantly correlated with BMI&#44; WC&#44; and fat mass percentage&#44; particularly in girls&#44; showing strong gender dimorphism&#44; as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> More importantly&#44; it was also equally and moderately related to hs-CRP&#46; We further aimed to clarify the correlations between hs-CRP&#44; leptin&#44; BMI&#44; WC&#44; fat mass percentage and adiponectin&#46; With the exception of adiponectin&#44; which was inversely but directly related to hs-CRP&#44; all others were directly and moderately correlated with hs-CRP&#46; These trends highlight the role of adiposity and leptin as pro-inflammatory triggers in obesity&#44; and these were evident from our study&#44; regardless of age or pubertal status&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Evidence in animal studies suggests that leptin&#44; like interleukin-6&#44; is capable of directly stimulating the production of hepatic CRP&#44; thus maintaining a low-grade inflammatory state&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> It also appears to compromise nitric oxide bioavailability&#44; and hence contribute towards endothelial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In our study&#44; leptin was the best predictor of hs-CRP levels&#46; This observation may provide a clue to the link between adipocyte dysfunction&#44; inflammation and ultimately endothelial dysfunction&#46; In contrast to our findings&#44; some authors have found that the best predictor of CRP is BMI&#44; while for others it was adiposity&#44;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#8211;39</span></a> but in these studies leptin was not included as a variable&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">As expected&#44; adiponectin showed gender dimorphism and was age-related&#44; being higher in girls than boys&#44; and decreased with age&#46; Our findings showed that&#44; in the obese group&#44; it was inversely correlated with BMI &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>-0&#46;212&#59; p&#61;0&#46;39&#41; and WC &#40;r&#61;-0&#46;278&#59; p&#61;0&#46;06&#41;&#44; but not correlated with hs-CRP or leptin&#46; In a study by Caprio et al&#46;&#44; an association was demonstrated between adiponectin levels and CRP&#44; whereas in ours&#44; as shown&#44; this was not the case&#46; In healthy individuals adiponectin has anti-atherogenic properties and studies have shown that&#44; in adults&#44; hypoadiponectinemia correlates with coronary lesions and is an independent risk factor for the progression of type 2 diabetes&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;41</span></a> In the light of our results&#44; we can infer that the presumptive loss of adiponectin&#39;s protective properties is yet another cardiovascular risk factor present in our population&#44; and if not abated may contribute to early onset cardiovascular disease and type 2 diabetes in this population&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">This study&#39;s main limitation relates to the sample size&#44; particularly the control group&#46; It also only includes a Caucasian population&#44; race thus being a possible source of bias in this study&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Based on our findings&#44; these markers may be considered for use in clinical practice for cardiovascular risk stratification in obese children&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical disclosures</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Protection of human and animal subjects</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Confidentiality of data</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Right to privacy and informed consent</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        ]
        10 => array:2 [
          "identificador" => "xack104187"
          "titulo" => "Acknowledgments"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-03-31"
    "fechaAceptado" => "2014-04-01"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec362873"
          "palabras" => array:5 [
            0 => "Pediatric"
            1 => "Obesity"
            2 => "High-sensitivity C-reactive protein"
            3 => "Adiponectin"
            4 => "Leptin"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec362872"
          "palabras" => array:5 [
            0 => "Pediatria"
            1 => "Obesidade"
            2 => "Prote&#237;na-C-reativa ultrassens&#237;vel"
            3 => "Adiponectina"
            4 => "Leptina"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pediatric obesity is increasingly prevalent in the Portuguese population&#46; Adipocyte dysfunction results in the expression of pro-inflammatory mediators that are responsible for the low-grade inflammatory process that characterizes obesity&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to investigate the relationship between markers of adiposity&#44; inflammation and adipokines in a Portuguese obese pediatric population&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">One hundred and twenty children of both sexes&#44; aged 6&#8211;17 years&#44; were included in this study&#46; The control group consisted of 41 healthy normal-weight children&#46; The variables analyzed were age&#44; gender&#44; body mass index&#44; waist circumference&#44; fat mass percentage&#44; high-sensitivity C-reactive protein &#40;hs-CRP&#41;&#44; leptin and adiponectin&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There were significant differences between controls and obese children for all parameters analyzed&#46; In the obese group&#44; after controlling for age and gender&#44; hs-CRP &#40;p&#61;0&#46;041&#41;&#44; adiponectin &#40;p&#61;0&#46;019&#41; and leptin &#40;p&#60;0&#46;001&#41; still showed significant statistical differences&#46; A direct correlation was found between hs-CRP&#44; leptin&#44; body mass index and waist circumference&#44; the strongest being with leptin &#40;r&#61;0&#46;568&#59; p&#60;0&#46;001&#41;&#46; This trend remained statistically significant&#44; regardless of gender or pubertal age&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Considering the role of leptin&#44; adiponectin and hs-CRP in the genesis of endothelial dysfunction&#44; they may be used in clinical practice for risk stratification&#44; as well as in the assessment of weight control programs&#46;</p>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A obesidade pedi&#225;trica &#233; prevalente na nossa popula&#231;&#227;o&#46; A adiposidade resulta na express&#227;o de marcadores pr&#243;-inflamat&#243;rios que s&#227;o respons&#225;veis pelo processo de inflama&#231;&#227;o de baixo grau que caracteriza a obesidade&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Tivemos como objetivo avaliar a rela&#231;&#227;o entre marcadores de adiposidade&#44; inflama&#231;&#227;o e adipocinas num grupo de crian&#231;as portuguesas obesas&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;das no estudo 120 crian&#231;as obesas&#44; entre os 6 e 17 anos de idade&#46; O grupo controlo continha 41 crian&#231;as saud&#225;veis&#44; sem excesso de peso&#44; dentro da mesma faixa et&#225;ria&#46; As vari&#225;veis analisadas foram&#58; idade&#44; g&#233;nero&#44; &#237;ndice de massa corporal&#44; circunfer&#234;ncia abdominal&#44; percentagem de massa gorda&#44; prote&#237;na C-reativa ultra-sens&#237;vel&#44; leptina e adiponectina&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Todos os par&#226;metros analisados encontravam-se significativamente mais elevados no grupo de crian&#231;as obesas&#46; No grupo obeso&#44; ap&#243;s avalia&#231;&#227;o por regress&#227;o log&#237;stica&#44; ajustando &#224; idade e g&#233;nero&#44; a prote&#237;na C-reativa ultra-sens&#237;vel &#40;p&#61;0&#44;041&#41;&#44; adiponectina &#40;p&#61;0&#44;019&#41; e leptina &#40;p&#60;0&#44;001&#41;&#44; mantiveram significado estat&#237;stico&#46; Os marcadores de adiposidade correlacionaram-se diretamente com a leptina &#40;p&#61;0&#44;001&#41; e inversamente com a adiponectina &#40;p&#61;0&#44;029&#41;&#46; Encontr&#225;mos tamb&#233;m uma correla&#231;&#227;o direta entre a prote&#237;na C-reactiva ultra-sens&#237;vel&#44; leptina&#44; &#237;ndice de massa corporal e circunfer&#234;ncia abdominal&#44; sendo a correla&#231;&#227;o mais robusta com a leptina &#40;&#961;&#61;0&#44;568&#59; p&#60;0&#44;001&#41;&#46; Esta tend&#234;ncia manteve-se independentemente do g&#233;nero ou idade puberal&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#245;es</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Considerando a rela&#231;&#227;o da leptina&#44; adiponectina e prote&#237;na C-reativa na g&#233;nese da disfun&#231;&#227;o endotelial&#44; estes poder&#227;o ser &#250;teis na pr&#225;tica di&#225;ria para estratifica&#231;&#227;o de risco&#44; assim como&#44; para avaliar medidas implementadas nos programas para redu&#231;&#227;o de peso em crian&#231;as obesas&#46;</p>"
      ]
    ]
    "nomenclatura" => array:1 [
      0 => array:3 [
        "identificador" => "nom0005"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0075">Abbreviations</span>"
        "listaDefinicion" => array:1 [
          0 => array:1 [
            "definicion" => array:5 [
              0 => array:2 [
                "termino" => "BMI"
                "descripcion" => "<p id="par0220" class="elsevierStylePara elsevierViewall">body mass index</p>"
              ]
              1 => array:2 [
                "termino" => "FM&#37;"
                "descripcion" => "<p id="par0225" class="elsevierStylePara elsevierViewall">fat mass percentage</p>"
              ]
              2 => array:2 [
                "termino" => "hs-CRP"
                "descripcion" => "<p id="par0235" class="elsevierStylePara elsevierViewall">high-sensitivity C-reactive protein</p>"
              ]
              3 => array:2 [
                "termino" => "TNF-&#945;"
                "descripcion" => "<p id="par0240" class="elsevierStylePara elsevierViewall">tumor necrosis factor alpha</p>"
              ]
              4 => array:2 [
                "termino" => "WC"
                "descripcion" => "<p id="par0245" class="elsevierStylePara elsevierViewall">waist circumference</p>"
              ]
            ]
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; FM&#37;&#58; fat mass percentage&#59; WC&#58; waist circumference&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as means &#177; standard error of the mean &#40;SEM&#41;&#46;</p>"
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                  \t\t\t\t">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Mean &#177; SEM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Mean &#177; SEM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;73&#177;0&#46;270&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;038<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">BMI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">28&#46;465&#177;0&#46;438&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">18&#46;933&#177;0&#46;429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">WC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">68&#46;16&#177;0&#46;861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FM&#37; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">36&#46;840&#177;0&#46;647&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&#46;544&#177;0&#46;526&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leptin &#40;ng&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28&#46;973&#177;1&#46;627&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;845&#177;0&#46;706&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adiponectin &#40;&#956;g&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;597&#177;0&#46;140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                    0 => array:2 [
                      "titulo" => "Adiponectin in childhood and adolescent obesity and its association with inflammatory markers and components of the metabolic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;C&#46; Winer"
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                      "doi" => "10.1210/jc.2006-0733"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2006"
                        "volumen" => "91"
                        "paginaInicial" => "4415"
                        "paginaFinal" => "4423"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16926246"
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        "identificador" => "xack104187"
        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0215" class="elsevierStylePara elsevierViewall">The authors would like to thank all those who contributed towards this study&#44; particularly those at the Department of Pediatric Cardiology of Coimbra Pediatric Hospital&#44; the Biochemical&#44; Hematological and Immunological Laboratories of Coimbra Pediatric Hospital and the Department of Physiology of Coimbra University Faculty of Medicine&#46;</p>"
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Informação do artigo
ISSN: 08702551
Idioma original: Inglês
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