This proposal will provide the PI formal and informal education in clinical research through mentors, course work, seminars, and the pursuit of a patient-oriented research project examining the relationship between obstructive sleep apnea (OSAS) and metabolic syndrome. Metabolic syndrome is a precursor to Type 2 diabetes (T2DM) and cardiovascular disease. Independent of obesity, OSAS is a risk factor in adults for insulin resistance and hypertension, both components of metabolic syndrome. Alterations in the endocrine system and in inflammatory markers have been observed in adult OSAS and may directly contribute to metabolic syndrome while disturbances in adipose tissue, active in both hormone and cytokine production, have recently been implicated in metabolic syndrome. The increasing prevalence of pediatric obesity and T2DM suggests OSAS should also be evaluated as a link to metabolic syndrome in children. We hypothesize that the repeated arousals from sleep and/or hypoxemia of pediatric OSAS lead to an inflammatory cascade, including alterations in adipokines, and enhanced sympathomimetic output which contribute to blood pressure elevations and decreased insulin sensitivity and that treatment of OSAS reverses these disturbances. We will perform polysomnography and detailed metabolic studies in obese and non-obese children with and without OSAS, and these studies will be repeated following treatment of children with OSAS to address our SPECIFIC AIMS: 1) To determine whether children with OSAS have decreased insulin sensitivity that correlates with severity of OSAS, 2) To determine whether children with OSAS have increased circulating inflammatory markers, disturbances in adipokines, and elevated catecholamine secretion that correlate with insulin sensitivity, and 3) To determine whether effective treatment of OSAS reverses insulin resistance, metabolic, and inflammatory changes. The PI, whose primary career goal is to become a clinical researcher with expertise in endocrine co-morbidities of pediatric disease, will use this study as a mechanism for career development: 1) to solidify her skills as a clinical investigator by working with experts in pediatric clinical research at CHOP and its GCRC, 2) to participate in formal education in clinical research, pharmacology, and neurobiology at The University of Pennsylvania, and 3) to continue education in diabetes and endocrinology through local and national conferences.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23RR021973-01
Application #
6960163
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2005-08-01
Project End
2010-05-31
Budget Start
2005-08-01
Budget End
2006-05-31
Support Year
1
Fiscal Year
2005
Total Cost
$133,272
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Kelly, Andrea; Brooks, Lee J; Dougherty, Shayne et al. (2011) A cross-sectional study of vitamin D and insulin resistance in children. Arch Dis Child 96:447-52
Brodsky, Jill; Dougherty, Shayne; Makani, Ramkrishna et al. (2011) Elevation of 1-hour plasma glucose during oral glucose tolerance testing is associated with worse pulmonary function in cystic fibrosis. Diabetes Care 34:292-5
Kelly, Andrea; Dougherty, Shayne; Cucchiara, Andrew et al. (2010) Catecholamines, adiponectin, and insulin resistance as measured by HOMA in children with obstructive sleep apnea. Sleep 33:1185-91
Kelly, Andrea; Tang, Randy; Becker, Susan et al. (2008) Poor specificity of low growth hormone and cortisol levels during fasting hypoglycemia for the diagnoses of growth hormone deficiency and adrenal insufficiency. Pediatrics 122:e522-8
Kelly, Andrea; Schall, Joan I; Stallings, Virginia A et al. (2008) Deficits in bone mineral content in children and adolescents with cystic fibrosis are related to height deficits. J Clin Densitom 11:581-9