Childhood obesity is associated with a high degree of metabolic disturbance in children from Brazilian semi-arid region.

Projected to impact 310 million children by the next decade, childhood obesity is linked to serious health issues like metabolic disturbance and cardiovascular diseases. This study introduces a novel approach for the integrated assessment of inflammatory, glycemic and lipid disorders in obese children in resources-limited settings and also identifies key factors contributing to these changes. Conducting a cross-sectional analysis of 231 children aged 5-12 years from public schools in Brazil's semi-arid region, the research involved collecting medical history, anthropometric measurements, and blood samples to analyze glycemic and lipid profiles, along with C-reactive protein levels. We used an adapted the Molecular Degree of Perturbation model to analyze deviations in metabolic markers from a healthy control group. Statistical analyses included Mann-Whitney and Fisher exact tests, backward logistic regression, and hierarchical cluster analysis. The study identified a direct and independent association between elevated Metabolic Disturbance Degree and both overweight and obesity in children, with significant differences in CRP, Triglycerides, and HDL levels noted between obese and healthy-weight groups. The findings highlight the critical need for early detection and comprehensive understanding of obesity-related changes to mitigate the severe health risks associated with childhood obesity.

Association between Childhood Overweight and Altered Concentrations of Circulating Amino Acids.

(1) Background: Dysregulated serum amino acids (AA) are known to be associated with obesity and risk of Type 2 Diabetes (T2D) in adults, and recent studies support the same notion in the pubertal age. It is, however, unknown whether childhood overweight may already display alterations of circulating AA. (2) Methods: We used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)-targeted metabolomics to determine plasma concentrations of AA and AA-related molecules in 36 children aged 7-12 years with normal weight or overweight. Clinical and anthropometric parameters were measured. (3) Results: Overweight in children is associated with an altered AA profile, with increased branched-chain amino acids (BCAA) and decreased glycine levels, with no clinically manifested metabolic conditions. Moreover, z-BMI was positively and negatively correlated with BCAA and glycine levels, respectively, even after adjustment for age and gender. We also found a correlation between the AA profile and clinical parameters such as lipids profile and glycemia. (4) Conclusions: A pattern of low glycine, and increased BCAA is correlated to z-BMI, total cholesterol, and triglycerides in overweight but otherwise healthy children. Our data suggest that, in childhood overweight, AA disturbances may precede other clinical parameters, thus providing an early indicator for the later development of metabolic disease.

Presence of metabolic syndrome markers in very low birth weight ex-premature infants during early adolescence.

OBJECTIVES: To investigate the association of growth patterns with overweight/obesity and markers of metabolic syndrome in ex-premature adolescents; to assess the relationship between the increase (1 SD) in Z-score weight at term and at 2 years with outcomes in adolescents with or without intrauterine growth restriction; and to evaluate the association between the Cook criteria and overweight/obesity according to body mass index. METHODS: Cohort, retrospective, analytical study. Population: adolescents born weighting<1,500 g. RESULTS: One hundred twenty-seven adolescents (11.3 years) were included. There is an association between the 1 SD increase in the percentile (Pc) of weight at 40 weeks and at 2 years in the population with adequate birth weight (PCA) with insulin levels, resistance, and sensitivity at 11 years. Catch-up at 2 years was associated with significantly higher proportion of HDL value<41 (18.75 vs. 5.36 %) OR 4.08 95% CI (1.04-16.05) p=0.031. Overweight/obesity was associated with waist circumference index>0.5, HDL<41, and with blood pressure greater than Pc 90 for sex and height. CONCLUSIONS: In preterm infants, a 1 SD increase in weight Z score at 40 weeks and 2 years was predictive of metabolic and cardiovascular disorders in adolescence.

Mediation effect of body mass index on the association between serum magnesium level and insulin resistance in children from Mexico City.

BACKGROUND/OBJECTIVES: Reduced serum magnesium (Mg) levels have been associated with obesity, insulin resistance (IR), type 2 diabetes, and metabolic syndrome in adults. However, in the children population, the evidence is still limited. In this cross-sectional study, we aimed to analyze the association of serum Mg levels with the frequency of overweight and obesity and cardiometabolic traits in 189 schoolchildren (91 girls and 98 boys) between 6 and 12 years old from Mexico City. SUBJECTS/METHODS: Anthropometrical data were collected and biochemical parameters were measured by enzymatic colorimetric assay. Serum Mg level was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. RESULTS: Serum Mg level was negatively associated with overweight (Odds ratio [OR] = 0.377, 95% confidence interval [CI] 0.231-0.614, p < 0.001) and obesity (OR = 0.345, 95% CI 0.202-0.589, p < 0.001). Serum Mg level resulted negatively associated with body mass index (BMI, ß = -1.16 ± 0.26, p < 0.001), BMI z-score (ß = -0.48 ± 0.10, p < 0.001) and TyG index (ß = -0.04 ± 0.04, p = 0.041). Through a mediation analysis was estimated that BMI z-score accounts for 60.5% of the negative association of serum Mg level with IR (Sobel test: z = 2.761; p = 0.005). CONCLUSION: Our results evidence that BMI z-score mediate part of the negative association of serum Mg level and IR in Mexican schoolchildren.

Inverse associations of cord blood mitochondrial DNA copy number with childhood adiposity.

OBJECTIVE: The objective of this study was to examine associations between umbilical cord mitochondrial DNA copy number (mtDNAcn) and adiposity across childhood. METHODS: In a prospective birth cohort of Dominican and African American children from New York City, New York (1998-2006), mtDNAcn was measured in cord blood. Children (N = 336) were evaluated for their height, weight, and bioimpedance at age 5, 7, 9, and 11 years. We used linear mixed-effects models to assess associations of mtDNAcn tertiles in cord blood with child BMI, BMI z scores, fat mass index, and body fat percentage. Latent class growth models and interactions between mtDNAcn and child age or child age2 were used to assess associations between age and adiposity trajectories. RESULTS: BMI was, on average, 1.5 kg/m2 higher (95% CI: 0.58, 2.5) in individuals with mtDNAcn in the low- compared with the middle-mtDNAcn tertile. Results were similar for BMI z score, fat mass index, and body fat percentage. Moreover, children in the low-mtDNAcn group had increased odds of being in an "increasing" or "high-stable" adiposity class. CONCLUSIONS: Lower mtDNAcn at birth may predict greater childhood adiposity, highlighting the potential key role of perinatal mitochondrial function in adiposity during development.

Responsiveness on metabolic syndrome criteria and hepatic parameters after 12 weeks and 24 weeks of multidisciplinary intervention in overweight adolescents.

PURPOSE: This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24 weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. METHODS: The study comprised 94 overweight adolescents, aged between 10 and 16 years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45 min of indoor cycling, 45 min of walking, and 20 min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. RESULTS: The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). CONCLUSION: Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. LEVEL OF EVIDENCE: Level I, evidence obtained from well-designed controlled trials randomization. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.

Emerging evidence for the opposite role of circulating irisin levels and brown adipose tissue activity measured by infrared thermography in anthropometric and metabolic profile during childhood.

Irisin is an adipomyokine that increases browning of adipose tissue and thermogenesis, thereby protecting against obesity and insulin resistance. However, the correlation between irisin, brown adipose tissue (BAT), and childhood obesity, as well as its association with an increased risk of developing metabolic diseases, has not been completely elucidated. This study aimed to investigate the association between irisin levels and BAT activity measured by infrared thermography among children and verify their correlation with anthropometric and metabolic parameters. This study included 42 children with normal weight and 18 overweight/obese children. Anthropometric data, irisin levels, lipid and glucose profile were evaluated. The percentage of the thermally active portion of the supraclavicular area (%AreaSCR) before and after a cold stimulus was measured by infrared thermography, and the differences between the percentages of thermally active (Δ%AreaSCR) was calculated as an index of BAT activation. The results were correlated with anthropometric and metabolic parameters. Circulating irisin levels was positive correlated with age (rho=0.327, P= 0.011), body mass index (BMI) (rho=0.707, P<0.001), waist circumference (rho=0.624, P<0.001), total cholesterol (rho=0.361, P=0.044), triglycerides (rho=0.419, P=0.001), and low-density lipoprotein cholesterol (LDLc) (rho=0.381, P= 0.003). Active BAT was negatively correlated with BMI, waist circumference, triglycerides, LDLc and irisin levels. We observed that normal weight children increased significantly the Δ% AreaSCR as compared to overweight/obese children. In conclusion, circulating irisin levels and BAT activity appear to have opposing roles, since normal weight children had greater BAT activity and lower circulating levels of irisin.

Prevalence and Clinical Significance of Autoantibodies in Children with Overweight and Obesity with Nonalcoholic Fatty Liver Disease.

OBJECTIVES: To evaluate the prevalence and clinical significance of autoantibodies in children with overweight and obesity with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) compared with those with autoimmune liver disease (ALD). STUDY DESIGN: This was a retrospective, cross-sectional study of children with a biopsy-proven diagnosis of NAFL, NASH, autoimmune hepatitis (AIH), or primary sclerosing cholangitis (PSC) and a body mass index (BMI) >85th percentile treated between 2007 and 2016. RESULTS: A total of 181 patients were identified, including 31 (17%) with NAFL, 121 (67%) with NASH, 12 (6.6%) with ALD (AIH, PSC, or overlap), and 17 (9.4%) with combined ALD and NAFLD. Antinuclear antibody (ANA), anti-actin antibody, and anti-liver kidney microsomal (LKM) antibody were positive in 16.1%, 13.8%, and 0%, respectively, of the patients with NAFL and in 32.8%, 15.5%, and 0%, respectively, of those with NASH. Total immunoglobulin G (IgG) was elevated in 27.3% of the patients with NAFL and in 47.7% of those with NASH, but in 100% of those with ALD. The positive predictive value of LKM was 100% for ALD but only 29% for ANA and 46% for anti-actin antibody. CONCLUSIONS: False-positive rates of autoantibodies were higher in pediatric patients with overweight and obesity with NAFLD compared with the general adult population. Positive LKM had the highest specificity and positive predictive value, and elevated IgG level had the highest sensitivity for ALD. The presence of autoantibodies does not signal more severe NAFLD in children. BMI >98th percentile seems to be an important breakpoint above which ALD is less likely.

High uric acid levels in overweight and obese children and their relationship with cardiometabolic risk factors: what is missing in this puzzle?

OBJECTIVES: The prevalence of hyperuricemia, a common disorder, has been increasing. Moreover, the association between obesity, serum uric acid levels, and cardiometabolic markers in children is unclear. Therefore, this study aimed to analyze the inter-relationships between these factors in a sample of children aged 6-12 years. METHODS: We evaluated 764 children and stratified them according to their body mass index (BMI). Blood pressure and uric acid, creatinine, lipid, and glycemic profiles were evaluated, and the estimated glomerular filtration rate (eGFR) and the homeostatic model assessment for insulin resistance (HOMA-IR) index were calculated. RESULTS: There was a significant linear trend of increasing systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol (LDLc), uric acid, insulin levels, and HOMA-IR index values corresponding with overweight and obese groups; however, high-density lipoprotein cholesterol (HDLc) levels decreased with increasing obesity. The mean creatinine level and eGFR were similar across all BMI groups. Uric acid levels were significantly correlated with BMI (r=0.527), waist circumference (r=0.580), SBP (r=0.497), DBP (r=0.362), TG (r=0.534), total cholesterol (r=0.416), LDLc (r=0.286), HDLc (r=-0.248), insulin (r=0.613), and HOMA-IR index (r=0.607). Multiple regression analyses showed that BMI (B=0.071; SE=0.012; p<0.001), TG (B=0.004; SE=0.001; p<0.001), LDLc (B=0.003; SE=0.001; p=0.006), and insulin (B=0.066; SE=0.007; p<0.001) (R2=0.460) were significant predictors of increased uric acid levels and explained 46% of the variability in uric acid in these children. CONCLUSIONS: Our findings suggest that overweight or obese children are more likely to have higher uric acid levels. Moreover, several cardiometabolic risk factors were strongly associated with high uric acid levels.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents.

BACKGROUND: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. OBJECTIVE: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. METHODS: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). RESULTS: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8-76.0] vs. 23.5 ng/mL [95% CI: 3.2-33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7-26.5] vs. 15.9 ng/mL [95% CI: 9.4-18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599-0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554-0.819, p = 0.008), considered fair. CONCLUSIONS: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice.

Sex Differences in MicroRNA Expression and Cardiometabolic Risk Factors in Hispanic Adolescents with Obesity.

OBJECTIVE: To evaluate sex differences in microRNA (miRNA) expression, anthropometric measures, and cardiometabolic risk factors in Hispanic adolescents with obesity. STUDY DESIGN: Cross-sectional study of 68 (60% male) Hispanic adolescents with obesity, aged 13-17 years, recruited from a pediatric weight management clinic. We used small RNA sequencing to identify differentially expressed circulating miRNAs. We used ingenuity pathway analysis and David bioinformatic resource tools to identify target genes for these miRNAs and enriched pathways. We used standard procedures to measure anthropometric and cardiometabolic factors. RESULTS: We identified 5 miRNAs (miR-24-3p, miR-361-3p, miR-3605-5p, miR-486-5p, and miR-199b-3p) that differed between females and males. miRNA targets-enriched pathways included phosphatidylinositol 3-kinase-protein, 5' AMP-activated protein kinase, insulin resistance, sphingolipid, transforming growth factor-ß, adipocyte lipolysis regulation, and oxytocin signaling pathways. In addition, there were sex differences in blood pressure, skeletal muscle mass, lean body mass, and percent body fat. CONCLUSIONS: We have identified sex differences in miRNA expression in Hispanic adolescents relevant to cardiometabolic health. Future studies should focus on sex-specific mechanistic roles of miRNAs on gene pathways associated with obesity pathophysiology to support development of precision cardiometabolic interventions.

CXCL8 expression and methylation are correlated with anthropometric and metabolic parameters in childhood obesity.

Childhood obesity is a global and increasing health issue. Inflammation and dysregulated adipose tissue secretion are common findings in obesity and have been related to poor metabolic function. Given that DNA methylation impacts gene expression and is responsive to environmental changes, we aimed, in addition to characterize the patients in anthropometric and biochemical terms, to determine the expression of cytokines and adipokines, assess the methylation on regulatory regions of the genes that code for these molecules, and investigate the association of the expression and gene methylation with anthropometric and biochemical parameters in childhood obesity. Obese children present dyslipidemia, dysregulated serum levels of adipokines and their ratios, altered leukocytic expression of cytokines, and higher methylation at the CXCL8 promoter as compared to the control group. However, no significant results were observed in the fasting plasma glucose levels or the methylation of TGFB1, LEP, and the enhancer region of ADIPOQ. We also found negative correlations of CXCL8 expression with anthropometric and biochemical parameters, and positive correlation of CXCL8 promoter methylation and the serum levels of hepatic enzymes. Our results indicate that changes in metabolic parameters observed in childhood obesity are associated with the expression of adipokines and cytokines, and the methylation status at the CXCL8 promoter. CXCL8 may be a key factor for these alterations, as it correlates with many of the parameters assessed in the present study.

Serum leptin as a mediator of the influence of insulin resistance on hepatic steatosis in youths with excess adiposity.

BACKGROUND AND AIMS: The relationship between insulin resistance (IR) and hepatic steatosis (fatty liver) is well known; however, the extent to which the satiety hormone leptin acts as a confounder or mediator in this relationship is uncertain. We examined whether the association between IR and hepatic steatosis is mediated by leptin in Colombian adolescents with excess adiposity. METHODS AND RESULTS: A total of 122 adolescents (mean age: 13.4 years; 68% girls) participated in the study. We assessed body composition, hepatic steatosis (as defined by the controlled attenuation parameter [CAP]), cardiometabolic risk factors (body mass index, waist circumference, body composition), biochemical variables (leptin, insulin, glucose, lipid profile, cardiometabolic Z-score, transaminases, etc.), and physical fitness (cardiorespiratory fitness and grip strength). Partial correlation, regression, and mediation analyses were conducted using the Barron and Kenny framework. RESULTS: Ninety-two youths (75.4%) had IR. Mediation analysis revealed a positive relationship between Homeostasis Model Assessment-IR (HOMA-IR) and CAP (ßdir = 3.414, 95% confidence interval [CI]: 1.012 to 5.816, p < 0.001), which was attenuated when leptin was included in the model, thus indicating that leptin mediates this relationship (ßind = 1.074, 95% CI: 0.349 to 2.686, p < 0.001). The percentage of the total effect mediated by leptin was 21%. Regarding sex, the mediation effect of leptin remains significant among boys (ßind = 0.962, 95% CI: 0.009 to 2.615, p < 0.001), but not in girls (ßind = 0.991, 95% CI: 1.263 to 5.483, p = 0.477). CONCLUSIONS: The findings are clinically relevant to consider leptin levels as a surrogate marker of insulin sensitivity when assessing youths with excess adiposity and/or suspected Nonalcoholic hepatic steatosis or nonalcoholic fatty liver disease (NAFLD).

Relationship of age at menarche and serum leptin with the metabolically unhealthy phenotype in adolescents.

INTRODUCTION: Objective: to analyze the relationship of age at menarche and leptin with the metabolically healthy (MH) and metabolically unhealthy (MUH) phenotypes in adolescent girls in different body mass index (BMI) categories. Method: an observational and cross-sectional study consisting of 139 female adolescents attended to at the Adolescent Reference Center in Macaé, Rio de Janeiro. Menarche was classified as early (EM) when the first menstruation occurred at or before 11 years of age; normal menarche (NM) was categorized at ages 12 to 14; menarche was considered late (LM) when it occurred at age 15 or older. The factors required to ascertain the subjects' phenotype, as well as their leptin levels, weight, and height, were measured and their BMIs were calculated. The girls were classified as MH or MUH based on the NCEP-ATP III criteria as adapted for children and adolescents. Results: 82 % (n = 114) of the girls were classified as MH and 18 % (n = 25) as MUH. Mean age at menarche was 11.79 ± 1.39 years. There was a higher prevalence of MUH amongst the girls who had EM (p = 0.04). A higher inadequacy of serum leptin concentrations was found in girls who had EM (p = 0.05) and in those classified as MUH (p = 0.01). The adolescents who were severely obese exhibited inadequate leptin levels (p < 0.01) and had gone through EM (p = 0.02). A total of 8.1 % (n = 7) of the normal-weight girls were classified as MUH, and 29.4 % (n = 5) of those who were severely obese were classified as MH (p < 0.01). Conclusion: early menarche and high serum leptin concentrations are related with the MUH phenotype in adolescent girls in different BMI categories.

INTRODUCCIÓN: Objetivo: analizar la relación de la edad de la menarquia y los niveles de leptina con los fenotipos metabólicamente saludables (MS) y metabólicamente no saludables (MNS) en adolescentes de diferentes categorías de índice de masa corporal (IMC). Método: estudio observacional y transversal compuesto por 139 adolescentes de sexo feminino, atendidas en el Centro de Referencia para Adolescentes de Macaé, Río de Janeiro. La menarquia se clasificó como precoz (MP) cuando se produjo la primera menstruación a o antes de los 11 años de edad; la menarquia normal (MN) se clasificó como aquella sucedida a la edad de 12 a 14 años; la menarquia se consideró tardía (MT) cuando ocurrió a los 15 años o más. Se midieron los factores necesarios para determinar el fenotipo de los sujetos, y se midieron sus niveles de leptina, peso y altura, y se calculó su IMC. Las adolescentes se clasificaron como MS y MNS según los criterios de NCEP-ATP III, adaptados para niños y adolescentes. Resultados: el 82 % (n = 114) de las adolescentes se clasificaron como MH y el 18 % (n = 25) como MUH. La edad media de la menarquia fue de 11,79 ± 1,39 años. Hubo una mayor prevalencia de MUH entre las adolescentes que tenían MP (p = 0,04). Se encontró una mayor insuficiencia de las concentraciones séricas de leptina en las adolescentes que tenían MP (p = 0,05) y en aquellas clasificadas como MNS (p = 0,01). Las adolescentes que eran severamente obesas exhibieron niveles inadecuados de leptina (p < 0,01) y habían pasado por una MP (p = 0,02). El 8,1 % (n = 7) de las adolescentes de peso normal se clasificaron como MNS y el 29,4 % (n = 5) de las que eran severamente obesas se clasificaron como MS (p < 0,01). Conclusión: la menarquia temprana y las altas concentraciones séricas de leptina están relacionadas con el fenotipo MNS en las adolescentes de diferentes categorías de IMC.

Homocysteine levels and cardiovascular risk factors in children and adolescents: systematic review and meta-analysis.

CONTEXT: Studies have indicated that homocysteine levels are nontraditional markers for cardiovascular disease. The onset of atherosclerotic disease begins in childhood and adolescence; thus, prevention of its risk factors should occur early. OBJECTIVE: This systematic review and meta-analysis was conducted to summarize the association between high homocysteine levels and traditional cardiovascular risk factors in children and adolescents. DATA SOURCES: This systematic review and meta-analysis were developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the protocol was submitted to PROSPERO. Only observational studies in children and adolescents with homocysteine levels as an exposure variable and cardiovascular risk factors as outcome variables were included and searched in the following electronic bibliographic databases: PubMed/MEDLINE, Web of Science, Embase, Latin American and Caribbean Literature in Health Sciences, Ovid and Scopus. DATA EXTRACTION: Two authors independently extracted data from eligible studies. The methodological quality of the studies was assessed using the Newcastle-Ottawa scale. DATA ANALYSIS: Seven studies were included in the systematic review; they were published from 1999 to 2017, predominantly were of a cross-sectional design, and mainly evaluated adolescents. In the meta-analysis (n = 6), cross-sectional studies (n = 3) identified that high homocysteine levels were positive and weakly correlated with overweight in children and adolescents (odds ratio, 1.08; 95%CI, 1.04-1.11). CONCLUSION: High homocysteine levels were weakly associated with overweight in children and adolescents in the reviewed cross-sectional studies. However, for the other traditional cardiovascular risk factors, the findings, although important, were inconclusive. Additional robust longitudinal studies are recommended to be conducted to better identify these associations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42018086252.

Relations between asthma and obesity: an analysis of multiple factors / Relações entre asma e obesidade: análise de múltiplos fatores

ABSTRACT Objective: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. Methods: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. Results: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. Conclusions: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

RESUMO Objetivo: A asma e a obesidade são doenças prevalentes e inter-relacionadas. Na população pediátrica, o efeito da inflamação sistêmica associada à obesidade, levando à inflamação das vias aéreas, é controverso. Nosso objetivo foi comparar padrões inflamatórios, clínicos e espirométricos entre crianças obesas e aquelas com peso normal. Métodos: Setenta e nove meninos e meninas de 6‒10 anos de idade foram selecionados e divididos em quatro grupos: asmáticos obesos, asmáticos não obesos, não asmáticos obesos e não asmáticos não obesos. Além de dados clínicos e antropométricos, todas as crianças foram submetidas a espirometria e testes cutâneos para alérgenos inalantes. Também foram coletadas amostras de sangue para dosagem de citocinas e adipocinas. Resultados: Obesos asmáticos tiveram um controle significativamente pior da asma do que os não obesos (RP 4,9; IC95% 1,1‒22,1), independentemente do sexo, atividade física e atopia. Não foram observadas diferenças nos níveis de espirometria, citocinas Th1 e Th2 e adipocinas entre os quatro grupos. Os testes cutâneos foram positivos em 81,8 e 80% dos não obesos asmáticos e obesos asmáticos, respectivamente. Conclusões: O grau de controle da asma foi significativamente menor no grupo obeso, apesar de não ter havido diferenças nos achados espirométricos. Esse resultado sugere que fatores extrapulmonares podem ser responsáveis por esse perfil sintomático. A alta positividade do teste cutâneo nos dois grupos, considerado um bom marcador de atopia, demonstrou o componente atópico como preponderante na gênese da asma, tanto em crianças com obesidade quanto naquelas com peso normal.

RELATIONS BETWEEN ASTHMA AND OBESITY: AN ANALYSIS OF MULTIPLE FACTORS.

OBJECTIVE: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. METHODS: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. RESULTS: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. CONCLUSIONS: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

Association of the Triglyceride/High-Density Lipoprotein Cholesterol Index with Insulin Resistance in a Pediatric Population in Northeast Mexico.

Background: The present study aimed to determine the association of the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index with IR in pediatric patients with overweight (OW) and OB, to assess the ability of the TG/HDL-C index to predict IR, and to estimate the prevalence of IR and metabolic syndrome (MetS). Methods: A cross-sectional study comprised 628 Mexican children (2-16 years old) from the OB clinic. IR was estimated using the HOMA-IR index (‡2.5). The modified Adult Treatment Panel III criteria were used to define MetS. Correlation analyses and a receiver operating characteristic (ROC) curve were used to assess the association of the TG/HDL-C index with IR and to establish the best cutoff for the TG/HDL-C index. Results: About 79.3% of the children presented IR and 55.4% MetS. Common findings in patients with IR were acanthosis nigricans (94.8%) and a TG/HDL-C index ‡2.27 (70.5%). Considering all the patients with a high TG/HDL-C index, 78.4% presented MetS, and 88.0% IR. The area under the curve-ROC for the ability of the TG/HDL-C index to predict IR was 0.72 (P < 0.001), with a sensitivity of 70.5% and specificity of 63.1%. Conclusions: TG/HDL-C index is a feasible alternative to the HOMA-IR index to predict IR in Mexican children with OW or OB. It might be used to identify children with the greatest need for treatment interventions.

Prevalence of Combined Lipid Abnormalities in Brazilian Adolescents and Its Association with Nutritional Status: Data from the Erica Study.

Background: Cardiovascular diseases are the leading cause of death in Brazil and worldwide. The growing incidence of obesity in children and adolescents and its association with lipid abnormalities may worsen this scenario, mainly in developing countries where obesity has reached epidemic levels. Dyslipidemias have several patterns, and the combination of some lipid abnormalities may have higher atherogenic potential. Objectives: To evaluate the prevalence of single or multiple combined lipid abnormalities in adolescents and its association with nutritional status assessed by body mass index. Methods: Data were obtained from the Study of Cardiovascular Risks in Adolescents (ERICA), a school-based, national representative study with Brazilian adolescents between 12 and 17 years of age. Adolescents whose lipid profiles were available were included, and lipid abnormalities were defined as LDL-C ≥ 100 mg/dL, HDL-C < 45 mg/dL, and tryglicerides (TG) ≥ 100 mg/dL. We assessed the prevalence of single or combined lipid abnormalities and correlated this nutritional status with body mass index of low weight, normal, overweight, and obesity. Results: A total of 38,069 adolescents were included, with more than 24,000 of them presenting at least one lipid abnormality (64.7%), and 3.7% showing alterations in all of them. The most prevalent combination was high TG with low HDL-C levels. The higher the BMI, the more lipid abnormalities were found. Conclusions: In this large and representative sample of Brazilian adolescents, the majority had at least one lipid abnormality. Higher BMI was associated with a higher prevalence of combined lipid abnormalities. Highlights: - There is a high prevalence of Brazilian adolescents with dyslipidemias.- BMI was associated with a higher prevalence of combined lipid abnormalities.- BMI can be considered as an indicator of the diagnosis of dyslipidemia in adolescents.

Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity.

BACKGROUND AND AIMS: Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. METHODS AND RESULTS: Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (-12%), NEFA (-26%) and uric acid (-22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = -0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). CONCLUSION: GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.