Model-Based Studies of Autonomic and Metabolic Dysfunction in Sleep Apnea
Obesity and insulin resistance are highly prevalent in subjects diagnosed with sleep apnea. One factor common to obesity, sleep and insulin resistance is autonomic nervous system dysfunction, in particular, sympathetic overactivity. Although the causal links among these factors are not well understood, it is likely that the vicious cycle of interplay among these factors predisposes to the emergence of “metabolic syndrome”, a convergence of obesity, hypertension, insulin resistance and dyslipidemia that is appearing in epidemic proportions in the United States and other countries. This chapter provides an overview of the ongoing experimental and modeling studies in my laboratory aimed at elucidating and quantifying the relationships among autonomic dysfunction, insulin resistance and severity of sleep apnea in overweight subjects. These studies employ a “minimal modeling” approach to extract information characterizing autonomic function from noninvasive cardiorespiratory measurements. We subsequently determine the relationship of these model parameters to the parameters estimated from the Bergman minimal insulin-glucose model using data obtained from the frequently sampled intravenous glucose tolerance test performed on the same individuals.
KeywordsInsulin Resistance Heart Rate Variability Continuous Positive Airway Pressure Autonomic Function Intermittent Hypoxia
I thank the following colleagues and students for contributing to the implementation of the experimental studies and the analysis of the data collected: Sally Ward, MD, Thomas Keens, MD, Steven Mittelman, MD, Michael Goran, PhD, Daniel Lesser, MD, Winston Tran, MS, Flavia Oliveira, MS, and Ricardo Ortega. This work was supported in part by NIH Grants HL090451, EB001978, M01 RR00047, and the USC Center for Transdisciplinary Research on Energetics and Cancer (TREC U54 CA 116848).
- Belozeroff, V., Berry, R.B., Sassoon, C.S.H., and Khoo, M.C.K. (2002) Effects of CPAP therapy on cardiovascular variability in obstructive sleep apnea: a closed-loop analysis. Am. J. Physiol. 282, H110–H121.Google Scholar
- Harsch, I.A., Schahin, S.P., Radespiel-Troger, M., Weintz, O., Jahreiss, H., Fuchs, F.S., Wiest, G.H., Hahn, E.G., Lohmann, T., and Konturek, P.C. (2004) Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am. J. Respir. Crit. Care Med. 169, 156–162.CrossRefPubMedGoogle Scholar
- Khoo, M.C.K. (2000) Physiological control systems: Analysis, simulation and estimation. New York: Wiley.Google Scholar
- Task force of the european society of cardiology and the North American society of pacing and electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 93, 1043–1065.Google Scholar