Sleep apnea is a chronic condition associated with an increased risk of hypertension and cardiovascular disease. Recent data suggest that sleep apnea is also associated with metabolic dysfunction that is characterized by glucose intolerance and insulin resistance. Although several studies indicate that the association between sleep apnea and metabolic dysfunction is independent of confounders including obesity, it remains to be determined whether the association is causal. Moreover, whether intermittent hypoxemia and/or sleep fragmentation are in the putative causal pathway is unknown. The major objective of our proposal is to determine whether sleep apnea produces metabolic dysfunction and delineate the underlying mechanisms. Our primary hypothesis is that intermittent hypoxemia and recurrent arousals from sleep lead to acute and chronic changes in metabolic function.
In Specific Aim 1, we will examine whether nighttime and daytime profiles of metabolic function differ between patients with sleep apnea and control subjects matched on age, race, gender, and obesity. We hypothesize that, compared to control subjects, patients with sleep apnea will demonstrate: a) marked abnormalities in nighttime profiles of glucose, insulin, and insulin secretion rate; b) impairment in daytime glucose tolerance, insulin sensitivity, and glucose effectiveness; and c) an increase in sympathetic activity and serum levels of leptin, cortisol, IL-6, and TNF-ct that are independently correlated with the severity of intermittent hypoxemia and frequency of arousals.
In Specific Aim 2, we will examine whether experimental sleep fragmentation and sleep apnea (sleep fragmentation with intermittent hypoxemia) alter metabolic dysfunction in normal subjects. We hypothesize that: a) sleep fragmentation in normal individuals will alter nighttime profiles of glucose, insulin, and insulin secretion rate and worsen daytime measures of glucose tolerance, insulin resistance, and glucose effectiveness; b) intermittent hypoxemia in association with sleep fragmentation will potentiate the adverse effects of sleep fragmentation alone; and c) experimental sleep fragmentation and sleep apnea will increase sympathetic activity and serum levels of cortisol, leptin, TNF-alpha and IL-6 in association with impaired glucose homeostasis. Novel experimental paradigms have been developed to determine the independent roles of sleep fragmentation and sleep apnea on metabolic function. Given the epidemic of obesity and diabetes, understanding the role of sleep apnea as a risk factor for metabolic dysfunction has public health significance in terms of prevention and treatment of diabetes, hypertension, and cardiovascular disease.
| Aurora, R Nisha; Patil, Susheel P; Punjabi, Naresh M (2018) Portable Sleep Monitoring for Diagnosing Sleep Apnea in Hospitalized Patients With Heart Failure. Chest 154:91-98 |
| Aurora, R Nisha; Crainiceanu, Ciprian; Gottlieb, Daniel J et al. (2018) Obstructive Sleep Apnea during REM Sleep and Cardiovascular Disease. Am J Respir Crit Care Med 197:653-660 |
| Kaplan, Katherine A; Hardas, Prajesh P; Redline, Susan et al. (2017) Correlates of sleep quality in midlife and beyond: a machine learning analysis. Sleep Med 34:162-167 |
| Aurora, R Nisha; Putcha, Nirupama; Swartz, Rachel et al. (2016) Agreement Between Results of Home Sleep Testing for Obstructive Sleep Apnea with and Without a Sleep Specialist. Am J Med 129:725-30 |
| Aurora, R Nisha; Kim, Ji Soo; Crainiceanu, Ciprian et al. (2016) Habitual Sleep Duration and All-Cause Mortality in a General Community Sample. Sleep 39:1903-1909 |
| Nagayoshi, Mako; Punjabi, Naresh M; Selvin, Elizabeth et al. (2016) Obstructive sleep apnea and incident type 2 diabetes. Sleep Med 25:156-161 |
| Suresh, Karthik; Servinsky, Laura; Reyes, Jose et al. (2015) Hydrogen peroxide-induced calcium influx in lung microvascular endothelial cells involves TRPV4. Am J Physiol Lung Cell Mol Physiol 309:L1467-77 |
| Aurora, R Nisha; Swartz, Rachel; Punjabi, Naresh M (2015) Misclassification of OSA severity with automated scoring of home sleep recordings. Chest 147:719-727 |
| Moon, Karoline; Punjabi, Naresh M; Aurora, R Nisha (2015) Obstructive sleep apnea and type 2 diabetes in older adults. Clin Geriatr Med 31:139-47, ix |
| Kudchadkar, Sapna R; Yaster, Myron; Punjabi, Arjun N et al. (2015) Temporal Characteristics of the Sleep EEG Power Spectrum in Critically Ill Children. J Clin Sleep Med 11:1449-54 |
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