Obesity and Obstructive Sleep Apnea: Pathogenic Mechanisms and Therapeutic Approaches

Abstract

Obstructive sleep apnea is a common disorder whose prevalence is linked to an epidemic of obesity in Western society. Sleep apnea is due to recurrent episodes of upper airway obstruction during sleep that are caused by elevations in upper airway collapsibility during sleep. Collapsibility can be increased by underlying anatomic alterations and/or disturbances in upper airway neuromuscular control, both of which play key roles in the pathogenesis of obstructive sleep apnea. Obesity and particularly central adiposity are potent risk factors for sleep apnea. They can increase pharyngeal collapsibility through mechanical effects on pharyngeal soft tissues and lung volume, and through central nervous system-acting signaling proteins (adipokines) that may affect airway neuromuscular control. Specific molecular signaling pathways encode differences in the distribution and metabolic activity of adipose tissue. These differences can produce alterations in the mechanical and neural control of upper airway collapsibility, which determine sleep apnea susceptibility. Although weight loss reduces upper airway collapsibility during sleep, it is not known whether its effects are mediated primarily by improvement in upper airway mechanical properties or neuromuscular control. A variety of behavioral, pharmacologic, and surgical approaches to weight loss may be of benefit to patients with sleep apnea, through distinct effects on the mass and activity of regional adipose stores. Examining responses to specific weight loss strategies will provide critical insight into mechanisms linking obesity and sleep apnea, and will help to elucidate the humoral and molecular predictors of weight loss responses.

Characteristics of patients potentially eligible for pharmacotherapy for weight loss in primary care practice in the United States

“…Obesity is strongly associated with an increased prevalence of sleep apnea 25, 26. Sleep apnea severely impairs health‐related quality of life 26.…”

Effect of laparoscopic Roux-en-Y gastric bypass surgery on obstructive sleep apnea in a Chinese population with obesity and T2DM

“…In a randomized controlled study, John et al reported that bariatric surgery did not result in a significantly greater reduction in AHI than conventional weight loss therapy, although the former did result in more weight loss [25]. They suggested that the state rather than the extent of weight loss was important in generating an altered neurohumoral and metabolic-inflammatory milieu, influencing defects in neuromuscular responses to mechanical loads [26,27]. Furthermore, the modified gastrointestinal anatomy and physiology may influence the effect of bariatric surgery on OSA, although no evidence has been reported to date.…”

The Role of Phentermine/Topiramate Extended-release in the Treatment of Obesity and Obesity-related Adverse Health Consequences

“…22 Obesity has also been implicated in anatomical changes that predispose patients to upper airway obstruction and reduced neuromuscular control of the air passages during sleep. 23,24 Obesity accelerates the initial onset and progression of physical disability in older adults. 25 Maternal obesity is associated with an increased risk for congenital anomalies.…”