Obesity and metabolic dysfunction increase the risk of cancer incidence and mortality. Increases in obesity and associated metabolic dysfunction are likely partly attributable to modern lifestyles haracterized by high fat food intake and reduced physical activity, and such behaviors may begin in childhood. Insufficient sleep, increasingly common in adolescents, has been implicated as a risk factor for both obesity and metabolic dysfunction. In this project, we will define the relationship between a number of host risk factors operating during childhood and adolescence, including insufficient sleep and sleep apnea, to longitudinally measured changes in both weight and biochemical indices of metabolic pathways implicated in cancer. We will capitalize on access to a large population-based pediatric cohort, the Cleveland Children's Sleep and Health Study, in which multiple measures of behavioral, sleep and biochemical risk factors for obesity have been measured longitudinally. The sample includes 50% former preterm children and 41% ethnic minorities, providing opportunities to quantify and identify specific mediators of excess risk of obesity and metabolic dysfunction in vulnerable subgroups. We propose to study 600 cohort members at ages 16 to 19 years, obtaining current measures of metabolic function that have been implicated in cancer (i.e., sex hormone levels, insulin resistance, adipokines, growth factors). Anthropmetric measurements will quantify body weight, stature, and body fat distribution. Risk factor data include standardized assessments of nutritional intake and behavioral risk factors. Subjects also will undergo 5-7 day monitoring of physical activity level and sleep/wake behavior with actigraphy and an overnight sleep study. Combining these data with birth data and data collected at a previous 8 to 11 year old exam will allow us to address the hypothesis that weight gain is largest in adolescents with insufficient sleep, and such effects are independent of other behavioral risk factors; and that metabolic dysfunction is most marked in adolescents with sleep apnea and in those with rapid weight gain. Identification of risk factors for obesity and metabolic dysfunction, and their variation with demography and common behavioral factors, including the novel consideration of sleep behaviors, may help develop targeted interventions for high-risk children and elucidate important pathophysiological pathways that increase risk of several chronic health conditions, including cancer and diabetes.
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