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Children with a history of extrauterine growth restriction (EUGR), later at prepubertal age, exhibit an increased metabolic risk including risen insulin resistance and low-grade inflammation. However, the progression of such metabolic changes after puberty and the lasting health implications have not yet been investigated. The objective of this study was to ascertain whether young adults with a history of EUGR faced increased vulnerability to metabolic disorders. A study was conducted comparing a group of adults with a history of EUGR with a healthy reference group. A total of 110 young adults (36 from the EUGR group and 74 from the control group) were included. Anthropometric variables, blood pressure (BP), general biochemical parameters, plasma inflammatory biomarkers, and adipokines were assessed. Compared to the reference group, the EUGR group had a shorter height and body weight with higher lean mass and waist circumference, as well as a greater percentage of individuals with high BP. In addition, EUGR patients had higher values of insulin, HOMA-IR, nerve growth factor, and leptin, and lower levels of adiponectin and resistin. The present study suggests that young adults with a history of EUGR present increased metabolic risk factors therefore, clinical follow-up should be considered.

Nutritional support is an integral part of the supportive care of hematopoietic stem cell transplantation (HSCT) patients. Omega-3 fatty acids (n-3 FA) emulsions in parenteral nutrition (PN) may modify the inflammatory response. The purpose of this study is to compare plasma cytokine levels in children after HSCT using an n-3 FA-containing lipid emulsion (LE) and a soybean oil-based formulation in PN. A randomized double-blind controlled trial was conducted on 14 children following HSCT. Children were randomized to receive either a fish oil or a soybean oil LE. Blood samples were drawn at baseline, on Day 10 and after completion of PN to analyze plasma interleukin 1 beta (IL-1β), 2 (IL-2), 6 (IL-6), 8 (IL-8), 10 (IL-10), and tumor necrosis factor alpha (TNF-α). After 10 days of PN, there were no significant changes in interleukins levels when comparing the two groups or time points (baseline vs. Day 10 of PN). In children requiring PN >21 days, IL-10 and TNF-α levels (P ≤ 0.05) were lower in the fish-oil-containing LE group. Fish oil- and soybean oil-supplemented PN administered for at least 10 days does not cause inflammatory changes. Prolonged PN based on fish oil LE may modulate the inflammatory response.

Background/aims: We aimed to evaluate the use of a continuous metabolic syndrome (MetS) score and to assess the associations of this score with risk biomarkers of inflammation, endothelial damage and cardiovascular disease (CVD) in prepubertal children., Methods: A total of 677 prepubertal children (295 obese, 146 overweight, and 236 normal-weight) were recruited. MetS traits, markers of inflammation, endothelial damage and CVD risk were measured, and a continuous MetS score was calculated, consisting of the sum/5 of the standardised scores of the MetS components., Results: The continuous MetS score was significantly associated with active plasminogen activator inhibitor-1 (r = 0.406, p < 0.001), adiponectin (r = -0.212, p < 0.001), resistin (r = 0.263, p < 0.001), C-reactive protein (r = 0.254, p < 0.001), tumour necrosis factor alpha (r = 0.120, p = 0.003), myeloperoxidase (r = 0.188, p < 0.001) and sE-selectin (r = 0.278, p < 0.001). Children in the normal-weight, overweight and obese groups with MetS totalled 0 (0%), 1 (0.7%) and 24 (8.7%), respectively, whereas the at-risk children identified using the continuous MetS score in each group totalled 2 (0.85%), 17 (11.6%) and 167 (56.6%), respectively., Conclusions: The association of the continuous MetS score with specific risk biomarkers of inflammation, endothelial damage and CVD supports its use in the early identification of children at increased risk of metabolic dysfunction., (© 2015 S. Karger AG, Basel.)

Intra-uterine growth restriction (IUGR) may induce significant metabolic and inflammatory anomalies, increasing the risk of obesity and CVD later in life. Similarly, alterations in the adipose tissue may lead to metabolic changes in children with a history of extra-uterine growth restriction (EUGR). These mechanisms may induce alterations in immune response during early life. The aim of the present study was to compare pro-inflammatory markers in prepubertal EUGR children with those in a reference population. A total of thirty-eight prepubertal children with a history of EUGR and a reference group including 123 healthy age- and sex-matched children were selected. Perinatal data were examined. In the prepubertal stage, the concentrations of inflammatory biomarkers were measured in both groups. The serum concentrations of C-reactive protein (CRP) and plasma concentrations of hepatocyte growth factor (HGF), IL-6, IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, TNF-α and plasminogen activator inhibitor type 1 were determined. The plasma concentrations of inflammatory biomarkers CRP, HGF, IL-8, MCP-1 and TNF-α were higher in the EUGR group than in the reference group (P< 0·001). After adjustment for gestational age, birth weight and length, blood pressure values and TNF-α concentrations remained higher in the EUGR group than in the reference group. Therefore, further investigations should be conducted in EUGR children to evaluate the potential negative impact of metabolic, nutritional and pro-inflammatory changes induced by the EUGR condition.

Background: Variants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children., Methods: A multicentre case-control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student's t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis., Results: All anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin., Conclusions: We validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin.

Objective: Obesity is associated with a state of chronic low-grade inflammation. Myeloperoxidase (MPO) plays an important role in the initiation and progression of acute and chronic inflammatory diseases, such as cardiovascular disease (CVD). The objectives of the current study were to evaluate plasma MPO levels in prepubertal obese children and to determine whether MPO could be an early biomarker of inflammation and CVD risk., Research Design and Methods: In a prospective multicenter case-control study paired by age and sex of 446 Caucasian prepubertal children ages 6-12 years, 223 normal-weight and 223 obese children were recruited. Blood pressure, waist circumference, weight, and height were measured. In addition to MPO, glucose, insulin, metabolic lipid parameters, oxidized low-density lipoproteins, adiponectin, leptin, resistin, C-reactive protein (CRP), interleukin 6, tumor necrosis factor α, matrix metalloproteinase-9 (MMP-9), and plasminogen activator inhibitor 1 were determined., Results: We found that MPO was elevated in prepubertal obese children and that this enzyme was associated with such proinflammatory and cardiovascular risk biomarkers as CRP, MMP-9, and resistin. Insulin resistance calculated by the homeostatic assessment model was the best predictor of MPO., Conclusions: MPO is an early biomarker of inflammation associated with CVD risk in obese children at the prepubertal age.

White adipose tissue functions not only as an energy store but also as an important endocrine organ and is involved in the regulation of many pathological processes. The obese state is characterised by a low-grade systemic inflammation, mainly a result of increased adipocyte as well as fat resident- and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. In obesity, the pro- and anti-inflammatory effects of adipokines and cytokines through intracellular signalling pathways mainly involve the nuclear factor kappa B (NF-kappaB) and the Jun N-terminal kinase (JNK) systems as well as the I kappa B kinase beta (IKK-beta). Mitogen-activated protein kinase (MAPK) and extracellular-signal-regulated kinase (ERK) pathways, which lead to signal transducer and activator of transcription 3 (STAT3) activation, are also important in the production of pro-inflammatory cytokines. Obesity increases the expression of leptin and other cytokines, as well as some macrophage and inflammatory markers, and decreases adiponectin expression in adipose tissue. A number of cytokines, e.g. tumour necrosis factor alpha (TNF-alpha) and monocyte chemotactic protein 1 (MCP-1), and some pro-inflammatory interleukins, leuckocyte antigens, chemochines, surface adhesion molecules and metalloproteases are up-regulated whereas other factors are down-regulated. The present paper will focus on the molecular mechanisms linking obesity and inflammation with emphasis on the alteration of signalling and gene expression in adipose cell components.

ObjectiveTo evaluate the association between waist-to-height ratio (WHtR) and specific biomarkers of inflammation, CVD risk and endothelial dysfunction in prepubertal obese children.DesignProspective, multicentre case–control study matched by age and sex.SettingChildren were recruited between May 2007 and May 2010 from primary-care centres and schools in three cities in Spain (Cordoba, Santiago de Compostela and Zaragoza).SubjectsFour hundred and forty-six (223 normal weight and 223 obese) Caucasian prepubertal children aged 6–12 years.ResultsWHtR was higher in the obese than in the normal-weight children. Blood pressure, waist circumference, weight, height, insulin, plasma lipids, leptin, resistin, abnormal neutrophil and monocyte counts, C-reactive protein, IL-6, IL-8, TNF-α, myeloperoxidase, soluble intercellular adhesion molecule-1, selectin and plasminogen activator inhibitor-1 levels were higher in the obese than in the normal-weight group. Adiponectin and HDL-cholesterol were lower and glucose and metalloproteinase-9 showed no differences. Resistin, TNF-α and active plasminogen activator inhibitor-1 were associated with WHtR, a sensitive indicator of central obesity.ConclusionsOur results lead to the hypothesis that changes in biomarker levels of insulin resistance, inflammation and CVD risk before puberty might induce metabolic consequences of obesity in obese children before reaching adulthood. [ABSTRACT FROM AUTHOR]

Diet is a key factor for obesity development; however, limited data are available on dietary cluster analysis in children with obesity. We aimed to assess the associations between dietary patterns and obesity and several cardiometabolic markers. Anthropometry, bioelectrical impedance, blood pressure and plasma biomarkers of oxidative stress, inflammation and endothelial damage were determined in 674 Caucasian children, aged 5–16, with normal or excess weight. Using a food frequency questionnaire and cluster analysis, two consistent dietary patterns were shown, labeled as health conscious (HC) and sweet and processed (SP). The HC pattern included a greater proportion of participants with overweight/obesity than the SP cluster (80.1% vs. 63.8%). However, children with obesity within the HC cluster, showed less abdominal fat, through waist to hip (0.93 vs. 0.94) and waist to height (0.61 vs. 0.63) indexes (p < 0.01). Univariate general models showed several additional differences in cardiometabolic risk biomarkers in the global and stratified analyses, with a healthier profile being observed mainly in the HC cluster. However, multivariate models questioned these findings and pointed out the need for further studies in this field. Anyhow, our findings support the benefits of a healthy diet and highlight the importance of dietary patterns in the cardiometabolic risk assessment of children with overweight/obesity, beyond weight control. [ABSTRACT FROM AUTHOR]