Does Treating Obstructive Sleep Apnea in Obese Canadian Youth Improve Blood Sugar Control?
Condition: Obesity; Obstructive Sleep Apnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Observational

Summary: 
      To determine whether, in obese children with moderate-severe Obstructive Sleep Apnea who are
      prescribed Positive Airway Pressure(PAP) therapy, increased hours of PAP usage per night over
      a one-year period is associated with a greater improvement in HOMA-IR
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
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.
      
Keywords: Obesity; OSA; PAP therapy