Does Treating Obstructive Sleep Apnea in Obese Canadian Youth Improve Blood Sugar Control? A Multi-Centered Prospective Cohort Study

Rationale: The five-fold increase in prevalence of childhood obesity in Canada over the last 15 years has led to an increasing number of pediatric cases of obesity-related obstructive sleep apnea (OSA). Not only is the prevalence of OSA significantly higher among obese children compared with the general population, but in this group, routine treatment by adenotonsillectomy has a much lower cure rate. Instead, Positive Airway Pressure (PAP) treatment is usually prescribed. Other complications of obesity are also increasingly recognized in children, including metabolic disturbances with insulin resistance (IR). This is particularly concerning, since IR is an identified surrogate measure of future obesity-related sequelae, such as diabetes, dyslipidemia, cardiovascular disease (including hypertension, and heart rate disturbances), inflammation and impaired quality of life. Of particular interest, the IR related to obesity can be exacerbated by OSA and the severity of IR correlates with the severity of OSA. IR is measured using a homeostasis model assessment of insulin resistance (HOMA-IR) and is calculated from fasting blood glucose and insulin levels. In obese adults with OSA, HOMA-IR, as well as cardiovascular and other metabolic markers, has been shown to improve following PAP therapy. Such a study has not been done in children. We hypothesize that PAP treatment for obese children with moderate-severe OSA will improve markers of obesity-related disease.

Primary Objective: To determine whether, in obese children with moderate-severe OSA who are prescribed PAP therapy, increased hours of PAP usage per night over a one-year period is associated with a greater improvement in HOMA-IR. Secondary Objectives: To determine whether increased hours of PAP usage per night is associated with a greater improvement in the following outcomes: 1) sympathetic nervous system activation (systolic and diastolic hypertension, nocturnal hypertension, heart rate and heart rate variability); 2) inflammation 3) neurobehavioral and quality of life measures. Methods: Study design: prospective multi-centre cohort study. Study Population: Obese children (body mass index (BMI) ≥ 95th %ile for age and sex) 8-17 years old with moderate-severe OSA will be recruited for this study from four pediatric tertiary care centres across Canada. As per current standard of care, those children with moderate-severe OSA, defined as ≥ 10 obstructive events per hour on polysomnography, will be prescribed PAP treatment. Sample Size: We expect a medium effect size (0.5); therefore 10 subjects per parameter tested (n=4) in the regression model and 25% attrition requires the recruitment of 54 subjects. Measurements will be made at baseline and 12 months. Data collection will include HOMA-IR, 24-hr blood pressure measurements, electrocardiogram for heart rate and heart rate variability, C-reactive protein as a marker of inflammation, neurobehavioral/quality of life measures (Conners parent and teacher scales, Child Behavior Checklist and Pediatric Quality of Life Inventory) and physical activity questionnaire (Habitual Activity Estimation Scale (HAES)). Data Analysis: Multivariate linear regression analyses will be performed for our primary and secondary outcomes. Our dependent variable will be change in HOMA-IR; our primary independent variable will be average number of hours/night of PAP usage. Adjustment variables will be change in BMI %ile, pubertal stage (Tanner stage 1-2 vs.

3-5), and change in HAES. Similar analyses will be performed for our secondary outcomes.

Importance: Treatment of obesity-related OSA in adults has been shown to reduce morbidity and mortality. Our study is uniquely poised and timely, as it will be the first to examine the impact of PAP therapy in children on measures of insulin resistance and other obesity-related conditions. It will raise awareness of co-morbidities of obesity and OSA in childhood and support early intervention, before irreversible end-organ damage has occurred.