Sleep-disordered breathing (SDB) is a common condition that affects approximately 5% of all middle-aged and older adults in the general population. It is characterized by recurrent collapse of the upper airway during sleep and is associated intermittent hypoxemia and recurrent arousals. There is an emerging concept in the literature that SDB is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. In spite of the recent advances in understanding these associations, causal links are still not clear. SDB-related intermittent hypoxemia and sleep fragmentation can trigger a cascade of pathophysiologic events including sympathetic nervous system activation, alterations in neuroendocrine function, and release of inflammatory cytokines. However, empirical data on pathways that link SDB to metabolic dysfunction are lacking. The overall objective of current proposal is to examine the mechanisms through which SDB may lead to metabolic abnormalities. To accomplish our goals, we will employ a combination of human and animal experiments to determine whether sleep-related intermittent hypoxia and sleep fragmentation act through different pathways to alter glucose metabolism. We will also determine whether metabolic dysfunction in SDB is reversible with continuous positive airway pressure (CPAP) treatment. Specifically, we propose: 1. To determine the independent and combined effects of sleep-related intermittent hypoxia and sleep fragmentation on metabolic function and characterize mechanisms underlying the metabolic effects. 2. To examine whether treatment of SDB with CPAP improves metabolic function. Specifically, we propose a randomized, sham-controlled clinical trial in subjects with SDB to determine whether CPAP has salutary effects on metabolic function. 3. To investigate, in a murine model, the biologic mechanisms for altered glucose metabolism induced by chronic intermittent hypoxia and sleep fragmentation. The experiments outlined in this application will provide important mechanistic insight into the causal pathways that may link SDB and metabolic dysfunction. The significance of this proposal is that it will help clarify how SDB leads to cardiovascular health outcomes and open therapeutic strategies that could partially curtail the epidemic of insulin resistance, glucose intolerance, and type 2 diabetes mellitus.
Sleep disordered breathing or sleep apnea is a common condition that affects more than 12 million adults in the US and has been associated with daytime sleepiness, memory problems, high blood pressure, cardiovascular disease, and diabetes. The overall objective of this research proposal is to determine how sleep disordered breathing leads to insulin resistance, glucose intolerance, and diabetes. We will also investigate whether treatment of sleep disordered breathing with continuous positive airway pressure improves metabolic function.
|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|
|Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina et al. (2016) Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study. Am J Respir Crit Care Med 194:1007-1014|
|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 147:719-27|
|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|
|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|
|Polotsky, Vsevolod Y; Bevans-Fonti, Shannon; Grigoryev, Dmitry N et al. (2015) Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells of Healthy Volunteers. PLoS One 10:e0144725|
|Punjabi, Naresh M; Shifa, Naima; Dorffner, Georg et al. (2015) Computer-Assisted Automated Scoring of Polysomnograms Using the Somnolyzer System. Sleep 38:1555-66|
|Kudchadkar, Sapna R; Aljohani, Othman A; Punjabi, Naresh M (2014) Sleep of critically ill children in the pediatric intensive care unit: a systematic review. Sleep Med Rev 18:103-10|
Showing the most recent 10 out of 36 publications