This project will evaluate the association between obstructive sleep apnea (OSA) in childhood, and the presence of the """"""""metabolic syndrome"""""""".
Our aims are: 1. To confirm the association between OSA in children and the presence of known risk factors for future cardiovascular disease. 2. To confirm that the physiological disruptions caused by OSA can induce the same metabolic abnormalities in an animal model, and 3. To confirm that treatment of OSA can reverse the abnormalities underlying the metabolic syndrome. The metabolic syndrome is a combination of hypertension, insulin resistance, and dyslipidemia. The first abnormality to appear in children is insulin resistance. The presence of insulin resistance in children has been associated with development of all three abnormalities in adulthood, and thus with increased risk for later cardiovascular disease. Studying OSA in children provides a unique opportunity to study the mechanisms underlying the association between OSA, the metabolic syndrome, and cardiovascular disease. The majority of children with OSA are NOT obese, so it is possible to determine the relative contribution of factors including obesity, chronic sympathetic activation, and chronic inflammation, if a sufficiently large group is studied. Children who present to a sleep unit already have some combination of symptoms suggestive of OSA. Therefore, a parallel study will seek to understand the earliest associations between OSA and the metabolic syndrome. To do this, piglets will be exposed to repetitive hypercapnic hypoxia, and equivalent studies of metabolic abnormalities will be undertaken. This component of the study will examine the specific sequence of disturbances underlying the metabolic syndrome, with the goal of determining preventative strategies that could be translated into the clinical setting. Finally, children who have OSA will undergo treatment, followed by re-evaluation. If treatment of OSA can reverse the metabolic disturbances present in association with OSA, this will support the need for early and aggressive intervention in childhood OSA.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL070784-01
Application #
6530430
Study Section
Special Emphasis Panel (ZHL1-CSR-P (M1))
Program Officer
Twery, Michael
Project Start
2002-09-01
Project End
2006-07-31
Budget Start
2002-09-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$108,000
Indirect Cost
Name
Children's Hospital at Westmead
Department
Type
DUNS #
City
Westmead
State
Country
Australia
Zip Code
2145
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Lau, Tong-Lay; Kim, Chungho; Ginsberg, Mark H et al. (2009) The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling. EMBO J 28:1351-61
Tam, Charmaine S; Wong, Melanie; Tam, Kimberley et al. (2007) The effect of acute intermittent hypercapnic hypoxia treatment on IL-6, TNF-alpha, and CRP levels in piglets. Sleep 30:723-7
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