Dominique Haentjens

Sleep-disordered breathing in overweight and obese children and adolescents: prevalence, characteristics and the role of fat distribution

Aims: To determine the prevalence of sleep-disordered breathing (SDB) in a clinical sample of overweight and obese children and adolescents, and to examine the contribution of fat distribution. Methods: Consecutive subjects without chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or craniofacial syndrome were recruited. All underwent measurements of neck and waist circumference, waist-to-hip ratio, % fat mass and polysomnography. Obstructive apnoea index ⩾1 or obstructive apnoea–hypopnoea index (OAHI) ⩾2, further classified as mild (2⩽OAHI<5) or moderate-to-severe (OAHI⩾5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central sleep apnoea was diagnosed when central apnoeas/hypopnoeas ⩾10 s were present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation <89%. Subjects with desaturation ⩽85% after central events of any duration were also diagnosed with central sleep apnoea. Primary snoring was diagnosed when: snoring was detected by microphone and normal obstructive indices and saturation. Results: 27 overweight and 64 obese subjects were included (40 boys; mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children, 53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate-to-severe OSA and 17% had central sleep apnoea. Half of the patients with central sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of moderate-to-severe OSA. On the other hand, higher levels of abdominal obesity and fat mass were associated with central sleep apnoea. Conclusion: SDB is very common in this clinical sample of overweight children. OSA is not associated with abdominal obesity. On the contrary, higher levels of abdominal obesity and fat mass are associated with central sleep apnoea.

Sleep-disordered breathing, obesity, and airway inflammation in children and adolescents.

BACKGROUND To investigate the relationship between obstructive sleep apnea syndrome (OSAS) and exhaled nitric oxide (eNO) in overweight children and adolescents without asthma or atopy and to assess whether obesity per se is associated with increased airway inflammation. METHODS Consecutive overweight subjects without symptoms of asthma or allergy were recruited at a pediatric obesity clinic. A normal-weight control group without OSAS and asthma or allergy was also recruited. All subjects underwent polysomnography and two measurements of eNO (afternoon and morning after polysomnography). RESULTS Controlling for age, the mean (+/- SD) afternoon eNO concentration was significantly higher in the snoring group (14.1 +/- 1.1 parts per billion [ppb]) compared with the normal-weight group (10.1 +/- 0.8 ppb; p = 0.03) and with the overweight group with normal polysomnography findings (8.9 +/- 0.8 ppb; p = 0.007). The afternoon eNO concentration was also different between the OSAS group (11.9 +/- 1.0 ppb) and the overweight group with normal polysomnography findings (p = 0.03). Morning eNO values were higher in the OSAS group (12.3 +/- 1.1 ppb) than in the normal weight group (9.9 +/- 0.8 ppb; p = 0.047) and in the overweight control group (9.7 +/- 0.7 ppb; p = 0.02). BMI z score was not significantly correlated with afternoon eNO concentration or with morning eNO concentration. CONCLUSION This study illustrates that both habitual snoring and OSAS are associated with increased airway inflammation in overweight children as assessed by higher eNO levels. Furthermore, it was demonstrated that childhood obesity in the absence of sleep-disordered breathing is not associated with increased airway inflammation.

Sleep-disordered breathing: a new risk factor of suspected fatty liver disease in overweight children and adolescents?

IntroductionThe aim of this retrospective study was to investigate if sleep-disordered breathing (SDB) was an independent predictor of suspected fatty liver disease in a clinical sample of overweight children and adolescents.Materials and methodsConsecutive overweight and obese children attending a pediatric obesity clinic underwent polysomnography, fasting blood sample, and abdominal ultrasound.Results and discussionThe respiratory disturbance index, percentage of total sleep time with SO2 < 90%, and SaO2nadir were associated with higher alanine amino-transferases (ALT) independent of abdominal obesity. Multiple logistic regression selected waist circumference (odds ratio = 1.05; p = 0.05) and SaO2nadir (odds ratio = 0.87; p = 0.03) as predictors of suggestive fatty liver disease, defined as ALT > 40 U/L and/or hyperechoic liver on abdominal ultrasound. This study supports the association between the severity of SDB and suspected fatty liver disease in a clinical sample of overweight children and adolescents. We recommend more research on the influence of SDB on the development of fatty liver disease and on the effect of treating sleep apnea on liver function parameters.

Association Study and Mutation Analysis of Adiponectin Shows Association of Variants in APM1 with Complex Obesity in Women

We performed an association study and mutation analysis of the adiponectin (APM1) gene to study its involvement in the development of obesity. We also studied the interaction with peroxisome proliferator‐activated receptor γ (PPARγ). 223 obese women and 87 healthy female control subjects were used for association analysis. Mutation analysis was done on 95 morbidly obese adults and 123 overweight and obese children and adolescents. We selected 6 haplotype tagging SNPs in APM1 and the Pro12Ala variant (rs1805192) in PPARγ to study the interaction. The G allele of rs2241766 was more common in controls (cases 10.8% vs. controls 18.4%, nominal p = 0.011; OR = 0.57, nominal p = 0.018). The rs2241766/rs3774261 haplotype was also associated with obesity (nominal p = 0.004). Only the latter association remained significant after controlling for the False Discovery Rate. Resequencing of exon 2, exon 3 and intron 2 in 95 individuals did not reveal any SNPs in high linkage disequilibrium with rs2241766. No interaction with the Pro12Ala variant in PPARγ was detected. Mutation analysis of APM1 did not identify mutations. In conclusion, we found an association of an APM1 haplotype with obesity and found that APM1 mutations are not a common cause of monogenic obesity in our cohort.

Sleep-disordered breathing and systemic inflammation in overweight children and adolescents

OBJECTIVE To assess if the severity of sleep-disordered breathing (SDB) and mainly intermittent hypoxia is associated with increased peripheral leukocytes in overweight children and adolescents, controlling for adiposity and obesity-related metabolic abnormalities. METHODS Consecutive subjects were recruited at a pediatric obesity clinic. All subjects underwent polysomnography and a fasting blood sample. RESULTS In total, 95 subjects were included ( =11.1+/-2.6, 43 boys, body mass index, =2.3+/-0.5, 29 subjects were overweight and 66 obese). Total white blood cell count increased significantly by worsening of intermittent hypoxia. Total white blood cell count was correlated with the maximal degree of desaturation, independent of puberty, HOMA and HDL-cholesterol. Neutrophil levels were associated with the degree of desaturation, while controlling for puberty and HOMA. CONCLUSION This study supports the hypothesis of an independent interaction between intermittent hypoxia and nocturnal desaturation during sleep, and increased white blood cell and neutrophil levels in overweight and obese children and adolescents. This finding may contribute to the mechanisms linking SDB with increased cardiovascular morbidity.

Sleep-disordered breathing and proteinuria in overweight and obese children and adolescents.

Objectives: To assess whether sleep-disordered breathing (SDB) in overweight children and adolescents has an additional effect on the spectrum of urinary albumin to protein loss, as markers of early kidney dysfunction. Methods: Prospective study in a clinical sample of overweight children and adolescents. Each subject underwent anthropometry, blood sampling, oral glucose tolerance test and polysomnography. From a 24-hour urine collection, albumin excretion rate and total urinary protein to creatinine ratio (UPCR) were calculated. Results: 94 nondiabetic subjects were included (mean age = 11.0 ± 2.5, 42 boys). Average BMI z-score was 2.25 ± 0.47 (26 overweight subjects and 68 obese subjects). There was no difference in albumin excretion rate or UPCR between subjects with and without SDB. None of the SDB parameters correlated with the transformed albumin excretion rate or UPCR. Albumin excretion rate significantly correlated with fasting insulin and C-peptide and with post-challenge glucose, insulin and C-peptide levels, while UPCR correlated with fasting and post-challenge C-peptide levels. Multiple regression indicated that post-challenge glucose levels were the most important predictors of albumin excretion rate. Conclusion: Insulin resistance, and not SDB, was associated with increased levels of albuminuria, indicating early renal dysfunction, in this clinical sample of overweight children and adolescents.