Obese youth (body mass index [BMI] greater than or equal to the 95th percentile) often snore, have symptoms of poor sleep, and are at higher risk for obstructive sleep apnea (OSA) as well as other health conditions than lean youth. OSA is a disorder characterized by narrowing of the airway, which results in repeated episodes of airflow cessation, oxygen desaturation (low oxygen levels in the blood) and disruption of normal sleep. Small, cross-sectional studies of obese youth have indicated that a significant percentage (30-60%) have some degree of OSA. In adults, OSA is not only associated with obesity, but has been independently associated with atherosclerotic cardiovascular disease, insulin resistance, and type 2 diabetes mellitus (T2DM). Whether not OSA leads to greater risk for T2DM in obese youth is not understood. These relationships are important to understand because if OSA in obese youth heightens the risk of developing T2DM, the translation of this finding would be to change clinical practice to improve the clinical outcomes of obese children. Bothe OSA and impaired glucose tolerance/T2DM have been shown to adversely affect cognitive function in adults. However, there are few data with regard to these relationships in overweight children. Therefore, our objective is to perform a pilot feasibility study to obtain preliminary data with respect to the association of presence/degree of OSA and 1) insulin sensitivity and secretion. 2) risk factors for cardiovascular disease, and 3) cognitive function in obese adolescents. We hypothesize that there is a positive relationship between OSA and insulin resistance that is independent of measures of adiposity.
Specific Aims of this pilot feasibility study are: 1) Evaluate the association between the presence/degree of OSA and in vivo insulin sensitivity, insulin secretion, and risk for T2DM, adjusted for measures of adiposity. In obese adolescents, 2) Evaluate the association between the presence/degree of OSA and markers of cardiovascular disease risk in obese adolescents;and 3) Evaluate whether or not standardized measures of cognitive function are adversely affected by OSA in obese adolescents, and explore the potential assoc9iation with the degree of insulin resistance. Study Subjects will include 20 adolsescents, aged 10-16. This study will be performed in the Pediatric Clinical Translational Research Center at Children's Hospital of Pittsburgh. Methods include hyperinsulinemic-euglycemic and hyperglycemic clamp tests, oral glucose tolerance testing, polysomnography (sleep study), body compostion evaluation, and cognitive function testing. The primary outcome measure is the assocaiton between the degree of OSA and arisk of type 2 diabetes based on the balance between insulin secretion and insulin sensitivity.
This pilot feasibility study will allow for critical assessment of possible associations between OSA, in vivo insulin resistance, markers of risk for CVD, and cognitive function in obese adolescents. The generation of such data is most crucial against the backdrop of the non-abating epidemic of childhood obesity, and will allow for advanced understanding of the pathogenesis of co-morbidities of obesity in youth. The relationships between OSA and metabolic risk factors in obese children are likely to be highly relevant and potentially modifiable, which holds the promise of facilitating improvement in the health care of obese children and improving clinical outcomes.
