Metabolic biomarkers in community obese children: effect of obstructive sleep apnea and its treatment

Highlights

• In obese children with obstructive sleep apnea syndrome (OSAS) the impact of treatment on metabolic function is unclear.

• Effective treatment of OSAS improves lipid profiles in obese children from the community.

• Effective treatment of OSAS could improve glucose metabolism in obese children with OSAS from the community.

Abstract

Objective

Obesity and obstructive sleep apnea in children have been associated with metabolic morbidities. The present study aimed to evaluate the presence of metabolic alterations among obese children recruited from the community, with and without obstructive sleep apnea syndrome (OSAS), and the impact of treatment of OSAS on metabolic profiles.

Methods

A cross-sectional, prospective, multicenter study of Spanish children aged 3–14 years with a body mass index (BMI) ≥95th percentile for age and sex were randomly selected in the first phase. Four groups emerged for follow-up: (1) no treatment; (2) dietary intervention; (3) surgical treatment of OSA; and (4) continuous positive airway pressure (CPAP) treatment of OSA. Fasting blood tests were performed at baseline (T0) and approximately one year after the intervention (T1).

Results

A total of 113 obese children with a mean age of 11.3 ± 2.9 years completed T0 and T1 assessments. Their mean BMI z-score at T1 was 1.34 ± 0.59, and mean Respiratory Disturbance Index was 8.6 ± 13.0 at T0 and 3.3 ± 4.0/hour total sleep time at T1. Only glucose fasting levels differed among metabolic parameters in obese children with OSAS and without OSAS at baseline (T0) (p = 0.018). There were statistically significant differences between surgically treated OSAS (p = 0.002), and CPAP-treated OSAS (p = 0.024) versus the non-OSAS group in the glucose levels between baseline (T0) and follow-up (T1) after controlling for age and change in BMI. Significant univariate associations between BMI and C-reactive protein, insulin, and homeostasis model assessment of insulin resistance emerged at both T0 and T1.

Conclusions

Concurrent obesity and OSAS could promote metabolic and inflammatory alterations, and the latter appeared to be sensitive to OSAS treatment outcomes.

ClinicalTrials.gov Identifier: NCT01322763.

Introduction

The prevalence of childhood obesity has reached epidemic proportions worldwide, with rates ranging from 7 to 22% in various countries [1]. In Spain, the enKID study, a cross-sectional epidemiological study of a representative sample of the Spanish population aged 2–24 years, has clearly established a high frequency of obesity among 6–13 year-old children, as evidenced by the 15.6% and 12% rates in boys and girls, respectively [2]. Furthermore, the ALADINO study (a community-based cross-sectional study), the aim of which was to determine the prevalence of overweight and obese children in Spain, was conducted in children aged between 6 and 9.9 years; the prevalence of obesity was 20.9% in boys and 15.5% in girls [3].

In this context, pediatric obesity has been recognized as a major medical and public health problem because it affects nearly every major organ system [4]. Possible complications include insulin resistance, dyslipidemia, and cardiovascular morbidity [4], [5], [6]. ‘Metabolic syndrome’ is a known risk factor for cardiovascular disease in adults, and refers to the clustering of insulin resistance, dyslipidemia, hypertension, and obesity. Furthermore, when metabolic syndrome occurs during childhood and/or adolescence, it indicates a high risk for cardiovascular morbidity during early adulthood [7], [8], [9].

Sleep disordered breathing (SDB) comprises a large group of associated conditions that include habitual snoring, upper airway resistance syndrome, hypoventilation, and obstructive sleep apnea syndrome (OSAS), all of which reflect different categories of respiratory alteration severity during sleep. Sleep disordered breathing – particularly OSAS – has been associated with a large spectrum of neurocognitive, behavioral, cardiovascular, and metabolic adverse consequences, the risk of which appears to be particularly exacerbated when concurrent obesity is present [10], [11]. In recent years, it has become apparent that the risk and severity of OSAS are markedly increased by the concurrent presence of obesity [12]. Indeed, the prevalence of OSAS in a community-based cohort study in obese children was high, ranging from 21.5 to 39.5% depending on the cut-off and nature of the polysomnographically-derived respiratory disturbance measures used [13].

Although OSAS in adults has been associated for several decades with increased risk for cardiovascular morbidities, it is only more recently that nocturnal elevation of systemic blood pressure and sustained diurnal hypertension [14], [15], [16], severity-dependent changes in left ventricular geometry and function [17], and abnormal endothelial function [18] have emerged and been recognized in children with OSAS, along with exacerbated cardiovascular risk, when insulin resistance is concurrently present [19], [20]. Thus, evaluation of the potential cardiometabolic burden that is inherently assignable to OSAS in children, and improved understanding of its reversibility would be of clear importance, considering that such morbidity is primarily silent in children and usually manifests much later in life, possibly too late for corrective measures to be implemented. To better understand the potentially adverse contributions of obesity and OSAS to metabolic regulation in children, a prospective study of obese children with OSAS and without OSAS was conducted [13], [21]. The following analyses were performed before and after treatment of OSAS: fasting levels of glucose (Glu), insulin (FPI), high sensitivity C-reactive protein (CRP), and plasma lipid profile concentrations.