The role of adipose tissue and subsequent liver tissue hypoxia in obesity and early stage metabolic dysfunction associated steatotic liver disease.

BACKGROUND: Obesity is linked to several health complication, including Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD). Adipose tissue hypoxia has been suggested as an important player in the pathophysiological mechanism leading to chronic inflammation in obesity, and in the progression of MASLD. The study aims to investigate the effect of progressive obesity on adipose and liver tissue hypoxia. METHODS: Male 8-week-old C57BL/6J mice were fed a high-fat high-fructose diet (HFHFD) or control diet (CD) for 4, 8, 12, 16 and 20 weeks. Serum ALT, AST and lipid levels were determined, and glucose and insulin tolerance testing was performed. Liver, gonadal and subcutaneous adipose tissue was assessed histologically. In vivo tissue pO2 measurements were performed in gonadal adipose tissue and liver under anesthesia. A PCR array for hypoxia responsive genes was performed in liver and adipose tissue. The main findings in the liver were validated in another diet-induced MASLD mice model, the choline-deficient L-amino acid defined high-fat diet (CDAHFD). RESULTS: HFHFD feeding induced a progressive obesity, dyslipidaemia, insulin resistance and MASLD. In vivo pO2 was decreased in gonadal adipose tissue after 8 weeks of HFHFD compared to CD, and decreased further until 20 weeks. Liver pO2 was only significantly decreased after 16 and 20 weeks of HFHFD. Gene expression and histology confirmed the presence of hypoxia in liver and adipose tissue. Hypoxia could not be confirmed in mice fed a CDAHFD. CONCLUSION: Diet-induced obesity in mice is associated with hypoxia in liver and adipose tissue. Adipose tissue hypoxia develops early in obesity, while liver hypoxia occurs later in the obesity development but still within the early stages of MASLD. Liver hypoxia could not be directly confirmed in a non-obese liver-only MASLD mice model, indicating that obesity-related processes such as adipose tissue hypoxia are important in the pathophysiology of obesity and MASLD.

Body composition helps to elucidate the different origins of low serum magnesium in children with obesity compared to children with type 1 diabetes.

Hypomagnesemia in patients with type 1 diabetes (T1D) as well as in obesity has been related to insulin resistance in adults, but not yet in pediatric patients. In this observational single-center study, we aimed to investigate the relation between the magnesium homeostasis, insulin resistance, and body composition in children with T1D and in children with obesity. Children with T1D (n = 148) and children with obesity and proven insulin resistance (n = 121) and healthy controls (n = 36) were included in this study. Serum and urine samples were collected to determine magnesium and creatinine. The total daily dose of insulin (for children with T1D), results from the oral glucose tolerance test (OGTT, for children with obesity), and biometric data were extracted from the electronic patient files. Furthermore, body composition was measured via bioimpedance spectroscopy. Serum magnesium levels were decreased in both children with obesity (0.87 ± 0.07 mmol/l) and children with T1D (0.86 ± 0.07 mmol/l) compared to healthy controls (0.91 ± 0.06; p = 0.005). A lower magnesium level was associated with more severe adiposity in children with obesity, while a worse glycemic control was associated with lower magnesium levels in children with T1D.   Conclusion: Children with T1D and children with obesity have decreased serum magnesium levels. An increased fat mass is associated with lower magnesium levels in childhood obesity, indicating that the adipose tissue is an important factor in magnesium homeostasis. In contrast, glycemic control was the main determining factor for serum magnesium levels in children with T1D. What is Known: • Hypomagnesaemia has been related to insulin resistance in both adults with T1D and adults with obesity. • There is an increasing prevalence of obesity and T1D in childhood, but little is known about the relationship between magnesium and insulin resistance in these children. What is New: • Both children with T1D and children with obesity have decreased serum magnesium levels. • In childhood obesity an increased fat mass is associated with lower magnesium levels, while glycaemic control is the main determining factor for serum magnesium in children with T1D.

The impact of obstructive sleep apnea on endothelial function during weight loss in an obese pediatric population.

BACKGROUND: Childhood obesity is an increasing problem with substantial comorbidities such as obstructive sleep apnea (OSA) and increased cardiovascular morbidity. Endothelial dysfunction is an underlying mechanism related to both obesity and OSA. RESEARCH QUESTION: To investigate the effect of weight loss on endothelial function and OSA in obese children and to determine whether a change in endothelial function can be linked to an improvement in OSA. METHODS: Obese children between 8 and 18 years of age were recruited while entering a 12-month inpatient weight loss program. Patients were followed at 3 study visits: baseline, after 10 months of weight loss, and 6 months after ending the program (18 months). Anthropometry and endothelial function (EndoPAT) were determined at all study visits. At baseline, sleep screening with a portable device (ApneaLink) was performed. This was repeated after 10 months if OSA was diagnosed at baseline. RESULTS: At baseline, 130 children were included, of which 87 had OSA (67%). Seventy-two patients attended the follow-up visit at 10 months, and 28 patients attended the follow-up visit at 18 months. The BMI z-score decreased after 10 months (from 2.7 (1.4-3.4) to 1.7 (0.5-2.7); p < 0.001) and remained stable at 18 months. Endothelial function improved significantly after weight loss, evidenced by a shorter time to peak response (TPR) and higher reactive hyperemia index (p = 0.02 and p < 0.001), and remained improved after 18 months (p < 0.001 and p = 0.007). After 10 months of weight loss, 10 patients had residual OSA. These patients had a higher TPR at 10 months (225 (75-285)s) than those without OSA (135 (45-225)s) and patients with a normalized sleep study (105 (45-285)s; p = 0.02). Linear mixed models showed that more severe OSA was associated with a worse TPR at baseline and less improvement after weight loss. CONCLUSION: Weight loss improves endothelial function in an obese pediatric population. However, even after weight loss, endothelial function improved less in the presence of OSA.

Improving Treatment Outcome in Children With Obesity by an Online Self-Control Training: A Randomized Controlled Trial.

Background: Currently available treatment programs for children with obesity only have modest long-term results, which is (at least partially) due to the poorer self-control observed within this population. The present trial aimed to determine whether an online self-control training, training inhibition, and redirecting attentional bias, can improve the short- and long-term treatment outcome of (in- or outpatient) child obesity treatment programs. Methods: In this double-blind multi-center randomized controlled trial (RCT), participants aged 8-18 years with obesity were allocated in a 1:1 ratio to receive an online self-control or sham training added to their in- or outpatient multidisciplinary obesity treatment (MOT) program. The primary endpoint was BMI SDS. Data were analyzed by linear mixed models and the main interactions of interest were randomization by time and randomization by number of sessions, as the latter was cumulatively expressed and therefore represents the effect of increasing dose over time. Results: One hundred forty-four inpatient (mean age 14.3 ± 2.2 years, BMI 2.7 ± 0.4 SDS, 42% male) and 115 outpatient children (mean age 11.9 ± 2.1 years, BMI 2.4 ± 0.4 SDS, 45% male) were included. Children's BMI lowered significantly during treatment in both the in- and outpatient treatment centers, p < 0.001. In a mixed model with BMI as dependent variable, randomization by time was non-significant, but the number of self-control trainings (randomization * number of sessions) interacted significantly with setting and with age (p = 0.002 and p = 0.047), indicating a potential effect in younger inpatient residents. Indeed, a subgroup analysis on 22 inpatient children of 8-12 years found a benefit of the number of self-control trainings on BMI (p = 0.026). Conclusions: The present trial found no benefit of the self-control training in the entire study population, however a subgroup of young, inpatient participants potentially benefited.

The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population With Obesity.

BACKGROUND: Childhood obesity has increased worldwide, becoming a significant public health concern. Brain-derived neurotrophic factor (BDNF) plays an important role in the central regulation of food intake and body weight, but little is known regarding its role in childhood obesity. Next to obesity, BDNF has been linked to obstructive sleep apnea (OSA) and endothelial dysfunction, two obesity-related comorbidities. The aim of this study is to investigate how BDNF, OSA and endothelial dysfunction interact in children with obesity and to determine the effect of weight loss on serum BDNF levels. METHODS: Children and adolescents with obesity aged 8-18 years who were enrolled in a multidisciplinary obesity treatment (MOT) in a tertiary hospital, were prospectively included. Several examinations were conducted during this MOT; at baseline, after 6 months and after 12 months, including the assessment of endothelial function, body composition measurements and a polysomnography. BDNF levels were measured on a serum sample by means of ELISA. RESULTS: A total of 103 patients with obesity was included, of which 20 had OSA (19.4%). BDNF levels were comparable in children with obesity and OSA and children with obesity but without OSA (26.75 vs. 27.87 ng/ml, p = 0.6). No correlations were found between BDNF and sleep-related variables or between BDNF and endothelial function parameters nor between BDNF and adiposity measures. To investigate if the interaction between OSA and endothelial dysfunction had an influence on BDNF levels, a general linear model was used. This model revealed that a diagnosis of OSA, as well as the interaction between OSA and maximal endothelial dilatation, contributed significantly (p = 0.03, p = 0.04, respectively) to BDNF levels. After 1 year of weight loss therapy, BDNF levels did not change (26.18 vs. 25.46 ng/ml, p = 0.7) in our population. CONCLUSION: BDNF concentrations were comparable in children with obesity, both with and without OSA, indicating that BDNF levels are not affected by OSA. However, we did find an interaction effect of OSA and endothelial function on BDNF levels.

A combined intrapleural administration of dornase alfa and tissue plasminogen activator is safe in children with empyema - A pilot study.

OBJECTIVE: There is still no consensus regarding the treatment of empyema in children. Intrapleural combination of tissue plasminogen activator and dornase alfa is a promising treatment for empyema in adults. The aim of this pilot study was to determine whether this combination is safe and successful in pediatric empyema. METHODS: Previous well children diagnosed with empyema as classified by the British Thoracic Society. After chest tube insertion, intrapleurally dornase alfa 2.5 mg for 2 days and tissue plasminogen activator 0.15 mg/kg for 3 days was given after which the chest tube was clamped for 4 h. Primary outcome was safety. RESULTS: Ten consecutive children were included (4 boys, aged 3.2 (1.3-15.0) years old). No serious adverse events were seen. One child developed urticaria but additional intervention or cessation of the trial was not needed. There was no bleeding or mortality and no additional procedures were performed. The median hospital stay after intervention was 7.5 days. CONCLUSIONS: The intrapleural treatment of dornase alfa and tissue plasminogen activator as treatment of empyema was safe in ten children with empyema. If confirmed in further studies, this combination of intrapleural therapy may improve the management of pediatric empyema.

Copy number variant analysis and expression profiling of the olfactory receptor-rich 11q11 region in obesity predisposition.

Genome-wide copy number surveys associated chromosome 11q11 with obesity. As this is an olfactory receptor-rich region, we hypothesize that genetic variation in olfactory receptor genes might be implicated in the pathogenesis of obesity. Multiplex Amplicon Quantification analysis was applied to screen for copy number variants at chromosome 11q11 in 627 patients with obesity and 330 healthy-weight individuals. A ± 80 kb deletion with an internally 1.3 kb retained segment was identified, covering the three olfactory receptor genes OR4C11, OR4P4, and OR4S2. A significant increase in copy number loss(es) was perceived in our patient cohort (MAF = 27%; p = 0.02). Gene expression profiling in metabolic relevant tissues was performed to evaluate the functional impact of the obesity susceptible locus. All three 11q11 genes were present in visceral and subcutaneous adipose tissue while no expression was perceived in the liver. These results support the 'metabolic system' hypothesis and imply that gene disruption of OR4C11, OR4P4, and OR4S2 will negatively influence energy metabolism, ultimately leading to fat accumulation and obesity. Our study thus demonstrates a role for structural variation within olfactory receptor-rich regions in complex diseases and defines the 11q11 deletion as a risk factor for obesity.

Clinical Predictors of Residual Sleep Apnea after Weight Loss Therapy in Obese Adolescents.

OBJECTIVE: To investigate clinical factors that could predict residual sleep-disordered breathing (SDB) after weight loss. STUDY DESIGN: Obese subjects between 10 and 19 years of age were recruited while entering an in-patient weight loss treatment program. All subjects underwent anthropometry and sleep screening using a portable device at baseline and after 4-6 months of therapy. Sleep and International Study of Asthma and Allergies in Childhood questionnaires were completed at baseline. RESULTS: A total of 339 patients were included. Median age was 15.4 years (10.1-19.1). Body mass index z score at baseline was 2.75 ± 0.42, and 35% of subjects were boys. SDB was present in 32%. After a mean decrease in body mass index z score of 32%, residual SDB was found in 20% of subjects with SDB at baseline. Subjects with more severe SDB (OR 1.18; CI 1.01-1.34; P = .02) and respiratory allergies (OR 7.85; CI 1.20-51.39; P = .03) were at higher risk of developing residual SDB, unlike age, sex, and anthropometric variables. CONCLUSIONS: Weight loss was successful for treating SDB in 80% of patients. More severe SDB and the presence of respiratory allergies at baseline were associated with a higher risk of residual SDB after weight loss.

Evaluation of a Role for NPY and NPY2R in the Pathogenesis of Obesity by Mutation and Copy Number Variation Analysis in Obese Children and Adolescents.

Neuropeptide Y (NPY) and its G protein-coupled NPY Y2 Receptor (NPY2R) are highly expressed in orexigenic NPY/Agouti-related peptide neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. As NPY and NPY2R are interesting candidate genes for obesity, we hypothesized that a genetic variation in these genes might be implicated in the pathogenesis of obesity. In the first part of this study, we performed a mutation analysis of the coding region of NPY and NPY2R with high-resolution melting curve analysis. For the highly conserved NPY gene, an extended population of 436 obese children and adolescents was screened, while for NPY2R, a smaller subset of 306 patients was used. A control population of 300 healthy individuals was screened for NPY2R to determine the general prevalence of the variants found among patients. Direct sequencing was performed for samples with melting patterns deviating from wild-type. In the second part of this study, Multiplex Amplicon Quantification (MAQ) analysis was performed in 308 obese children and adolescents to detect copy number variation (CNV) in the NPY2R region. Mutation analysis of the NPY gene led to the identification of one common missense variant (L7P; MAF 0.04), while the screening of the NPY2R gene resulted in the identification of one rare missense variant F87I in the patient population. In our CNV analysis, we could not identify copy number variation in the NPY2R region among obese children and adolescents. In summary, this study clearly indicates that genetic variation in NPY and NPY2R is at low frequency and thus does not make a major contribution to the obese phenotype in the general population.

Dynamics of persistent organic pollutants in obese adolescents during weight loss.

We have investigated the dynamics of various persistent organic pollutants (POPs) in the serum of 94 obese adolescents (34 boys and 60 girls: age range 11-19years) before (0M) and after 5months (5M) of undergoing weight loss treatment. Six groups of POPs, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and polybrominated diphenyl ethers (PBDEs), were detected in all samples in the decreasing order of median levels: DDTs>PCBs>HCB>HCHs>CHLs>PBDEs. Levels and patterns of POPs between boys and girls at two time-points were similar. DDTs (0M/5M; median: 31/42ng/g lw) and PCBs (0M/5M; median: 17/28ng/g lw) were the major POPs. PCB 153 (0M/5M; 33/34% of the sum PCBs) was the most dominant PCB congener, followed by PCB 138 (0M/5M; 31/31%) and PCB 180 (0M/5M; 13/12%), respectively. The most important PBDE congeners were BDE 47 and 153, although total PBDE levels were low and ranged between 0.63 and 0.88ng/g lw. In general, levels of POPs in the obese adolescents were lower than previously reported in Belgian adolescents and adults. Due to weight loss, serum levels (except PBDEs) increased significantly thereafter combined with a body weight decrease (from 4 to 42kg). Serum concentrations increased by 1-3.5% per kilogram weight loss and 1-2.5% per BMI z-score loss for most POPs. To our knowledge, this is the first report on the dynamics of POPs in obese adolescents during weight loss. Lipid-soluble contaminants were released from adipose tissue into the blood leading to redistribution into the body. Whether the increase in the internal exposure to POPs may adversely influence health remains to be determined.

Sleep-disordered breathing, systemic adipokine secretion, and metabolic dysregulation in overweight and obese children and adolescents.

OBJECTIVE: Obstructive sleep apnea (OSA) is common among overweight and obese children, and it is an independent risk factor for developing metabolic syndrome. However, the mechanisms linking OSA and metabolic syndrome are still unclear, but a role for adipose tissue dysfunction caused by intermittent hypoxia has been suggested. Therefore, the goal of this study was to investigate the relationship between OSA and systemic adipokine concentrations in overweight and obese children. METHODS: We included 164 overweight and obese children in a tertiary center and distributed them in groups based on their obstructive apnea-hypopnea index (111 controls, 28 mild OSA, 25 moderate-to-severe OSA). All subjects underwent polysomnography and a blood sample was taken to determine leptin, adiponectin, tumor necrosis factor alpha, and interleukin-6 levels. RESULTS: No significant differences were found in adipokine levels between subjects with or without OSA. Leptin correlated with oxygen desaturation index (r = -0.17, p = 0.03), adiponectin correlated with mean oxygen saturation (r = 0.24, p = 0.002) and with the percentage of sleep time with an oxygen saturation >95% (r = 0.25, p = 0.001). However, these associations did not persist after correction for adiposity. No correlations between interleukin-6 and tumor necrosis factor alpha, and OSA severity were found. CONCLUSION: These results suggest that serum adipokine levels are mostly dependent on central obesity, while they are not influenced by OSA in an obese pediatric population.

Sleep Complaints and Sleep Architecture in Children With Idiopathic Central Sleep Apnea.

STUDY OBJECTIVES: Idiopathic central sleep apnea (ICSA) is categorized as a type of nonhypercapnic central sleep apnea (CSA). Recurrent cessation and resumption of respiration leads to sleep fragmentation, which causes excessive daytime sleepiness, frequent nocturnal awakenings, or both. ICSA has been described in the adult population but there is limited information in children. The purpose of this study was to describe clinical manifestations and polysomnographic findings in children with ICSA. METHODS: A retrospective review of medical records and polysomnograms was performed for 14 pediatric patients with ICSA, 9 from Cincinnati Children's Hospital Medical Center and 5 from Antwerp University Hospital. Polysomnographic features of patients with ICSA were compared with those of nine age-matched control group subjects. Patients with CSA caused by medical or neurological disorders, medication use, or substance use were excluded. RESULTS: Sleep complaints were common in the 14 children with ICSA, including those with sleep-onset insomnia (7 children), frequent nighttime awakening (3 children), restless sleep (7 children), and daytime sleepiness (5 children). Symptoms of sleep-disordered breathing were noted in 11 of 14 subjects. Compared to that of the control group, sleep latency in the ICSA group was significantly prolonged (P < .05). The percentage of stage 2 sleep was significantly higher (P < .05), and slow wave sleep was significantly lower in patients with ICSA (P < .05). CONCLUSIONS: Similar to adult patients, children with ICSA present with complaints of insomnia, daytime sleepiness, and symptoms of obstructive sleep apnea. Analysis of polysomnograms reveals prolonged sleep latency, increased stage 2 sleep, and decreased slow wave sleep. Further studies are needed to assess mechanisms and the role of hypercapnic response in the pathogenesis of children with ICSA.

Sleep disordered breathing and autonomic function in overweight and obese children and adolescents.

Obstructive sleep apnoea (OSA), common in children with obesity, is associated with cardiovascular morbidity. Autonomic dysfunction has been suggested to be a key player in the development of these complications. We investigated the relationship between obesity, OSA and sympathetic activity in children. 191 children with obesity were included and distributed into two groups: 131 controls and 60 with OSA. Beat-to-beat RR interval data were extracted from polysomnography for heart rate variability analysis. Urinary free cortisol levels were determined. Urinary free cortisol did not differ between groups and was not associated with OSA, independent of the level of obesity. Differences in heart rate variability measures were found: mean RR interval decreased with OSA, while low/high-frequency band ratio and mean heart rate increased with OSA. Heart rate variability measures correlated with OSA, independent of obesity parameters and age: oxygen desaturation index correlated with mean heart rate (r=0.19, p=0.009) and mean RR interval (r= -0.18, p=0.02), while high-frequency bands and low/high-frequency band ratio correlated with arterial oxygen saturation measured by pulse oximetry (SpO2 ) (r= -0.20, p=0.008 and r= -0.16, p=0.04) and SpO2 nadir (r=0.23, p=0.003 and r= -0.19, p=0.02). These results suggest that sympathetic heart activity is increased in children with obesity and OSA. Measures of hypoxia were related to increased sympathetic tone, suggesting that intermittent hypoxia is involved in autonomic dysfunction.

Nucleotide variation of sFRP5 gene is not associated with obesity in children and adolescents.

Because sFRP5 was shown to be an important extracellular modulator of the Wnt pathway, regulating adipogenesis, we wanted to investigate the role of sFRP5 variants in human, monogenic obesity by performing mutation analysis. We screened the complete sFRP5 coding region in 622 obese children and adolescents and 503 lean control individuals by high-resolution melting curve analysis and direct sequencing. We found a total of 15 sequence variants in sFRP5, 10 of which resulted in a non-synonymous amino acid change. Five of these variants were, to our knowledge, not previously reported. For one of the variants (c.-3G>A), we identified a trend towards association between the variant frequency and the obese phenotype. We argue that, when looking at conservation and location inside known protein domains, several of the identified variants (D103N, A113V, K212N and H317L), may affect sFRP5 protein function. In addition, we found c.-3G>A, residing in the Kozak sequence, with a lower frequency in cases compared to controls. However, functional studies investigating the effect of sFRP5 variants on protein function are necessary to determine the true role of sFRP5 genetic variation in human, monogenic obesity.

CNV analysis and mutation screening indicate an important role for the NPY4R gene in human obesity.

OBJECTIVE: Genome-wide copy number variation (CNV) analyses have associated the 10q11.22 CNV with obesity. As the NPY4R gene is the most interesting candidate gene in this region, it was hypothesized that both genetic and structural variation in NPY4R might be implicated in the pathogenesis of obesity. METHODS: In the first part of this study, 326 children and adolescents with obesity and 298 healthy lean individuals were screened for CNV in the NPY4R-containing chr.10q11.22 region. In the second part of this study, a mutation screen for variants in the NPY4R coding region was performed in 356 children and adolescents with obesity and 337 healthy lean adults. RESULTS: Our CNV analysis demonstrated a significantly higher frequency of NPY4R containing 10q11.22 CNV loss in the patient population (P = 0.0003), while CNV gain in this region was more prevalent in the control population (P = 0.031). Mutation analysis resulted in the identification of 15 rare non-synonymous heterozygous variants. For two variants that could only be identified in the patient population, receptor dysfunction and thus a pathogenic effect were demonstrated. CONCLUSIONS: In conclusion, these data support an essential role for genetic and structural variation within the NPY4R gene in the pathogenesis of obesity.

C-reactive Protein as a Potential Biomarker of Residual Obstructive Sleep Apnea Following Adenotonsillectomy in Children.

STUDY OBJECTIVES: Adenotonsillectomy (AT) is first-line treatment for pediatric obstructive sleep apnea (OSA), with most children having improvements in polysomnography (PSG). However, many children have residual OSA following AT as determined through PSG. Identification of a biomarker of residual disease would be clinically meaningful to detect children at risk. We hypothesize serum high-sensitivity C-reactive protein (hsCRP), an inflammatory biomarker, is predictive of residual OSA following AT. METHODS: PSG was performed both preoperatively and postoperatively on children undergoing AT for the diagnosis of OSA. HsCRP serum concentrations were determined in all children pre-AT, and in most children post-AT. Resolution of OSA after AT was defined by a post-AT apnea-hypopnea index (AHI) < 1.5/h total sleep time (TST). Residual OSA was defined as a post-AT AHI > 5/h TST, which is considered clinically significant. RESULTS: AT significantly improved the AHI from 15.9 ± 16.4 to 4.1 ± 5.3/h TST in 182 children (P < 0.001). Of 182 children, residual OSA (post-AT AHI > 5) was seen in 46 children (25%). Among children who had hsCRP levels measured pre- and post-AT (n = 155), mean hsCRP levels pre-AT were 0.98 ± 1.91 mg/L and were significantly reduced post-AT (0.63 ± 2.24 mg/dL; P = 0.011). Stratification into post-AT AHI groups corresponding to < 1.5/h TST, 1.5/h TST < AHI < 5/h TST, and AHI > 5/h TST revealed post-AT hsCRP levels of 0.09 ± 0.12, 0.57 ± 2.28, and 1.49 ± 3.34 mg/L with statistical significance emerging comparing residual AHI > 5/h TST compared to post-AT AHI < 1.5/h TST (P = 0.006). Hierarchical multivariate modeling confirmed that pre-AT AHI and post-AT hsCRP levels were most significantly associated with residual OSA. CONCLUSIONS: Even though AT improves OSA in most children, residual OSA is frequent. Assessment of post-AT hsCRP levels emerges as a potentially useful biomarker predicting residual OSA.

Investigation of common and rare genetic variation in the BAMBI genomic region in light of human obesity.

The aim of this study was to confirm the previously identified link between BAMBI and human obesity by means of a genetic and functional analysis. We performed both a mutation analysis, using high-resolution melting curve analysis, and a genetic association study, including 8 common tagSNPs in the BAMBI gene region. Three of the identified genetic variants (R151W, H201R, and C229R) were evaluated for their Wnt signaling enhancing capacity in a Wnt luciferase reporter assay. Mutation screening of the BAMBI coding region and exon-intron boundaries on our population of 677 obese children and adolescents and 529 lean control subjects resulted in the identification of 18 variants, 10 of which were not previously reported and 12 of which were exclusively found in obese individuals. The difference in variant frequency, not taking into account common polymorphisms, between obese (3.1 %) and lean (0.9 %) subjects was statistically significant (p = 0.004). Our Wnt luciferase assay, using WT and mutant BAMBI constructs, showed a significantly reduced activity for all of the investigated variants. Logistic and linear regression analysis on our Caucasian population of 1022 obese individuals and 606 lean controls, did not identify associations with obesity parameters (p values >0.05). We found several rare genetic variations, which represent the first naturally occurring missense variants of BAMBI in obese patients. Three variants (R151W, H201R, and C229R) were shown to reduce Wnt signaling enhancing capacity of BAMBI and we believe this result should encourage further study of this gene in other obese populations. In addition, we did not find evidence for the involvement of BAMBI common variation in human obesity in our population.

The role of nocturnal pulse oximetry in the screening for obstructive sleep apnea in obese children and adolescents.

BACKGROUND AND AIM: Obesity is a known risk factor for the development of obstructive sleep apnea (OSA) in children. Early screening is essential because of the possible complications associated with OSA. At present, the gold standard for diagnosing OSA is polysomnography, which however has multiple limitations. The aim of this study is to examine the role of nocturnal oximetry as a screening tool for OSA in obese children and adolescents. MATERIALS AND METHODS: This retrospective study included obese children who underwent a polysomnography at the Antwerp University Hospital between November 2010 and May 2014. Their oximetries were scored manually, blinded for the polysomnography results, according to Brouilette et al. OSA was defined as an obstructive apnea-hypopnea index (oAHI) ≥ 2 on polysomnography. RESULTS: This study included 130 obese patients (38% boys, mean age 12 years). Polysomnography results determined 44 patients (34%) with a diagnosis of OSA. Oximetry results classified 16 patients as positive, 43 as negative, and 71 as inconclusive. Further analysis of the positive and negative oximetry results showed a sensitivity and specificity of 58% and 88%, respectively, with a negative and positive predictive value of 81% and 69%, respectively. A second analysis, using the oxygen desaturation index, showed inferior results in comparison to the score attained by Brouillette (sensitivity 57%, specificity 73%). CONCLUSIONS: These results suggest that oximetry alone is insufficient as a screening tool for OSA in obese children. Other screening methods need to be explored in the future.