Insulin Sensitivity, Serum Lipids, and Systemic Inflammatory Markers in School-Aged Obese and Nonobese Children

The impact of obesity as a systemic low-grade inflammatory process has only partially been explored. To this effect, 704 community-based school-aged children (354 obese children and 350 age-, gender-, and ethnicity-matched controls) were recruited and underwent assessment of plasma levels of fasting insulin and glucose, lipids, and a variety of proinflammatory mediators that are associated with cardiometabolic dysfunction. Obese children were at higher risk for abnormal HOMA and cholesterol levels. Furthermore, BMI z score, HOMA, and LDL/HDL ratio strongly correlated with levels of certain inflammatory mediators. Taken together, obesity in children is not only associated with insulin resistance and hyperlipidemia, but is accompanied by increased, yet variable, expression of markers of systemic inflammation. Future community-based intervention and phenotype correlational studies on childhood obesity will require inclusion of expanded panels of inflammatory biomarkers to provide a comprehensive assessment of risk on specific obesity-related morbidities

Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

<p>Abstract</p> <p>Introduction</p> <p>Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity.</p> <p>Methods</p> <p>A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65) and non-obese (NOB). Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135), corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped.</p> <p>Results</p> <p>Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values.</p> <p>Conclusions</p> <p>Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.</p

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children

Rationale: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea–hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. Methods: DeidentifiednSpO2 recordings froma total of 4,191 children originating from13 pediatric sleep laboratories around the worldwere prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. Measurements and Main Results: The automatically estimated apnea–hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). Conclusions: Neural network–based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.Supported in part by project VA037 U16 from the Consejer´ıa de Educacio´ n de la Junta de Castilla y Leo´ n and the European Regional Development Fund (FEDER), project RTC-2015-3446-1 from the Ministerio de Econom´ıa y Competitividad and FEDER, and project 153/2015 of the Sociedad Espan˜ ola de Neumolog´ıa y Cirug´ıa Tora´ cica (SEPAR). L.K.-G. is supported by NIH grant 1R01HL130984. M.F.P. was supported by a Fellowship Educational grant award from the Kingdom of Saudi Arabia. D.´A. was in receipt of a Juan de la Cierva grant from the Ministerio de Econom´ıa y Competitividad. The funders played no role in the study design, data collection, data analysis, interpretation, and writing of the manuscript

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children

Rationale: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea–hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. Methods: DeidentifiednSpO2 recordings froma total of 4,191 children originating from13 pediatric sleep laboratories around the worldwere prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. Measurements and Main Results: The automatically estimated apnea–hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). Conclusions: Neural network–based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.Supported in part by project VA037 U16 from the Consejer´ıa de Educacio´ n de la Junta de Castilla y Leo´ n and the European Regional Development Fund (FEDER), project RTC-2015-3446-1 from the Ministerio de Econom´ıa y Competitividad and FEDER, and project 153/2015 of the Sociedad Espan˜ ola de Neumolog´ıa y Cirug´ıa Tora´ cica (SEPAR). L.K.-G. is supported by NIH grant 1R01HL130984. M.F.P. was supported by a Fellowship Educational grant award from the Kingdom of Saudi Arabia. D.´A. was in receipt of a Juan de la Cierva grant from the Ministerio de Econom´ıa y Competitividad. The funders played no role in the study design, data collection, data analysis, interpretation, and writing of the manuscript

Endothelial dysfunction in obese non-hypertensive children without evidence of sleep disordered breathing

<p>Abstract</p> <p>Background</p> <p>Endothelial dysfunction is a complication of both obesity and obstructive sleep apnea syndrome (OSAS), the latter being highly prevalent among obese children. It is unknown whether obesity causes endothelial dysfunction in children in the absence of OSAS. This study examines endothelial function in obese and non-obese children without OSAS.</p> <p>Methods</p> <p>Pre-pubertal non-hypertensive children were recruited. Endothelial function was assessed in a morning fasted state, using a modified hyperemic test involving cuff-induced occlusion of the radial and ulnar arteries. The absence of OSAS was confirmed by overnight polysomnography. Anthropometry was also performed.</p> <p>Results</p> <p>55 obese children (mean age 8.6 ± 1.4 years, mean BMI z-score: 2.3 ± 0.3) were compared to 50 non-obese children (mean age 8.0 ± 1.6 years, mean BMI z-score 0.3 ± 0.9). Significant delays to peak capillary reperfusion after occlusion release occurred in obese compared to non-obese children (45.3 ± 21.9 sec <it>vs</it>. 31.5 ± 14.1 sec, p < 0.01), but no differences in the magnitude of hyperemia emerged. Time to peak reperfusion and percentage of body fat were positively correlated (r = 0.365, p < 0.01).</p> <p>Conclusions</p> <p>Our findings confirm that endothelial dysfunction occurs early in life in obese children, even in the absence of OSAS. Thus, mechanisms underlying endothelial dysfunction in pediatric obesity are operational in the absence of sleep-disordered breathing.</p

Metabolic Alterations and Systemic Inflammation in Obstructive Sleep Apnea among Nonobese and Obese Prepubertal Children

Rationale: Obstructive sleep apnea (OSA) has been associated with a higher prevalence and severity of the metabolic syndrome in adult patients, even after controlling for obesity. In contrast, OSA in prepubertal children does not appear to correlate with the magnitude of such metabolic derangements

C-reactive Protein, Obstructive Sleep Apnea, and Cognitive Dysfunction in School-aged Children

Rationale: Obstructive sleep apnea (OSA) in children is associated with substantial neurobehavioral and cognitive dysfunction. However, not all children with OSA exhibit altered cognitive performance