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AUTONOMIC AND METABOLIC EFFECTS OF OBSTRUCTIVE SLEEP APNEA IN CHILDHOOD OBESITY
by
Flavia Maria Guerra de Sousa Aranha Oliveira
____________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHYLOSOPHY
(BIOMEDICAL ENGINEERING)
August 2011
Copyright 2011 Flavia Maria Guerra de Sousa Aranha Oliveira
Object Description
| Title | Autonomic and metabolic effects of obstructive sleep apnea in childhood obesity |
| Author | Oliveira, Flavia Maria Guerra de Sousa Aranha |
| Author email | foliveir@usc.edu;flavia.sousa.aranha@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biomedical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2011-06-16 |
| Date submitted | 2011-07-22 |
| Date approved | 2011-07-22 |
| Restricted until | 2011-07-22 |
| Date published | 2011-07-22 |
| Advisor (committee chair) | Khoo, Michael C. K. |
| Advisor (committee member) |
D’Argenio, David Z. Ward, Sally L. Davidson Keens, Thomas G. |
| Abstract | The current evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to both autonomic dysfunction and impaired glucose metabolism. These relationships have been less well studied in children. Since sleep-disordered breathing occurs in over 13% of the obese pediatric population, knowledge about the autonomic and metabolic effects of OSA is crucial in determining the importance of OSA as an independent factor in promoting the development of childhood metabolic syndrome. The hypothesis in this study is that OSA severity in overweight/obese children is associated with both autonomic abnormality and insulin resistance. This study will also investigate if there is a direct association between autonomic dysfunction and insulin resistance. ❧ To evaluate this hypothesis, overnight polysomnographic studies and tests of metabolic and autonomic function were conducted in 22 obese male subjects (age: 13.4 ± 2.1 years (mean ± SD), BMI>95% for age) with varying degrees of OSA severity (obstructive apnea-hypopnea index (OAHI): 1-14.1 events/h; desaturation index: 0.1-40.1). Exclusion criteria included diabetes and treatment for OSA. ❧ Each subject participated in a series of procedures that included: (1) polysomnography; (2) morning fasting blood samples, followed by a frequently-sampled intravenous glucose tolerance test (FSIVGTT); (3) dual energy X-ray absorptiometry for assessing adiposity; and (4) measurement of respiration, heart rate and noninvasive continuous blood pressure during supine and standing postures. Insulin sensitivity, disposition index (a measure of pancreatic beta cell function) and other Bergman minimal model parameters were derived from the FSIVGTT data. Baroreflex gain and respiratory cardiac coupling gain, computed using a minimal model of cardiorespiratory control, were taken to represent indices of autonomic function. ❧ For this sample of patients, insulin sensitivity was found to decrease with desaturation index. Insulin resistance (as measured by the HOMA index) and fasting insulin levels were correlated positively with sleep fragmentation, as represented by the total arousal index (TAI). The HOMA index (p = 0.025) and fasting insulin levels (p = 0.017), but not fasting glucose, were found to be significantly correlated to insulin sensitivity. Baseline autonomic function was found to be uncorrelated with all indices of OSA severity. However, autonomic reactivity to orthostatic stress (supine to standing) decreased with increasing TAI. ❧ Baseline autonomic function and autonomic reactivity to orthostatic stress were not correlated to insulin sensitivity or any other measure of insulin resistance, contrary to initial expectations. However, autonomic reactivity was found to be correlated with insulin resistance when OSA severity is also considered in the multiple regression model. In this case, both autonomic reactivity and OSA severity were correlated with insulin resistance. ❧ Elevated fasting glucose levels were found to be correlated with smaller autonomic adjustments to postural change (as measured by the baroreceptor reflex reactivity) when controlling for age, adiposity, and sleep efficiency, indicating impaired autonomic reactivity. ❧ These combined results suggest that insulin resistance is related not only to intermittent hypoxia (high desaturation index) and sleep fragmentation (high TAI) that accompanies OSA, but also to increased OSA severity through autonomic dysfunction. An additional speculation is that increased levels of baseline sympathetic modulation related to decreased sleep efficiency further contribute to metabolic dysfunction by increased fasting glucose levels, through sympathetically induced glycogen breakdown and gluconeogenesis. |
| Keyword | autonomic nervous system; cardiorespiratory minimal model; childhood obesity; insulin resistance; obstructive sleep apnea; sleep disordered breathing |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Oliveira, Flavia Maria Guerra de Sousa Aranha |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-OliveiraFl-157-0.pdf |
Description
| Title | Page 1 |
| Full text | AUTONOMIC AND METABOLIC EFFECTS OF OBSTRUCTIVE SLEEP APNEA IN CHILDHOOD OBESITY by Flavia Maria Guerra de Sousa Aranha Oliveira ____________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHYLOSOPHY (BIOMEDICAL ENGINEERING) August 2011 Copyright 2011 Flavia Maria Guerra de Sousa Aranha Oliveira |
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