FAT AND FATIGUED: The Link Between Obesity and OSA

Imran Junaid, MD

Obstructive sleep apnea is a common sleep disorder with an estimated prevalence of 4–5% in the United States.¹ OSA is characterized by repeated partial or complete collapse of the upper airway during sleep, causing intermittent oxygen desaturations and sleep fragmentation. During sleep, OSA is generally associated with snoring, gasping or witnessed pauses in breathing. During wakefulness, it is associated with excessive daytime sleepiness and fatigue. OSA is a risk factor for cardiovascular disease and various metabolic disorders, including insulin resistance and metabolic syndrome.

Obesity, which is now recognized as a major public health concern, has been linked to multiple metabolic derailments. It results from an imbalance between energy intake and expenditure, generally due to increased consumption of energy-dense foods in combination with reduced physical activity. Obesity is a complex disease created by a multitude of factors, including chronic illness, hormonal changes, altered microbiome, psychological state, availability of nutritious foods, cultural attitudes and lack of access to exercise facilities.

About 70% of patients who suffer from OSA are obese,² while 40% of obese patients have OSA.¹ Higher body mass indexes correlate with the severity of OSA.³ Many factors contribute to this correlation.

Airway obstruction in OSA occurs when the nasopharynx and oropharynx are occluded by posterior movement of the tongue and soft palate against the posterior pharyngeal wall. In general, narrower airways are more prone to collapse. Obese patients have extrinsic narrowing of the area surrounding the collapsible region as well as regional soft-tissue enlargement.^4,5

In addition to localized upper airway fat deposition, central/android type fat deposition is an independent predictor for OSA, even in the non-obese. Visceral obesity leads to reduced lung volumes, which in turn reduce caudal traction of the upper airways, thus further increasing pharyngeal collapsibility.⁶ The fact that men store fat centrally may explain their higher rates of OSA when compared to women.

Beyond structural influence of obesity on the airways, hormonal dysregulation is another shared phenomenon of the two conditions. Leptin—a polypeptide hormone produced by adipocytes in proportion to fat mass—is a major player in appetite regulation in the hypothalamus.⁷ In a lean person, leptin is associated with states of satiety and is thought to control weight by regulating fat stores.

In obese patients and those with OSA, dysregulated elevated leptin levels persist.⁸ This persistence is thought to be related to leptin resistance. Researchers have hypothesized that leptin resistance contributes to a lack of satiation, leading to overeating. Leptin levels also positively correlate with worsening OSA, independent of weight.^9,10 In addition, leptin levels correlate with intermittent and continuous hypoxia in OSA. It is unclear if the leptin levels are causal or reactive to the hypoxia.¹¹

Ghrelin, commonly known as the hunger hormone, is a polypeptide produced by the gut. It is a short-lived neuropeptide that is suppressed with eating and increased with fasting. Ghrelin is the only known appetite-stimulating, or orexigenic, gut hormone.¹² Ghrelin levels increase with weight loss and sleep restriction, and correlate with severity of OSA.¹⁰

Treatment of OSA with continuous positive airway pressure (CPAP) leads to decreases in both leptin and ghrelin, thus helping to regulate appetite.¹⁰

In addition to its effects on satiety regulation, OSA may also lead to decreased energy expenditure. Multiple studies have demonstrated decreased exercise tolerance as well as decreased physical drive in patients with OSA^.13–15 A large study on patients with OSA found that maximal exercise capacity was less in those with OSA when compared to controls.¹⁴ With poor or fragmented sleep patterns, OSA patients also develop higher levels of fatigue.¹⁶ In addition, OSA may reduce motivation to exercise because patients with OSA have higher rates of depression.¹⁷

Inversely, losing weight helps cure OSA. Intentional weight loss has been shown to decrease the severity of OSA, based upon reductions in the Apnea-Hypoapnea Index.¹⁸ Weight loss also decreases collapsibility of the upper airway.¹⁹ Unfortunately, weight loss is not a complete or permanent fix for OSA. Some patients who lose weight and subsequently achieve a cure of their sleep apnea may later redevelop OSA on repeat polysomnograms after 1–2 years. This redevelopment occurs despite maintenance of the original weight loss.²⁰

Treating OSA can eventually lead to better outcomes for obesity. Studies of patients who were compliant with CPAP use were more likely than noncompliant patients to have significant weight loss (10 pounds or greater) on follow-up after 6 months. Compliance was described as using CPAP for at least 4 hours per night.²¹ However, recent data suggests that CPAP alone is not an effective tool for weight loss.²²

The relationship between obesity and OSA is complex. The metabolic derailment of OSA can lead to further weight gain, which can further exacerbate OSA. Conversely, weight loss is an important tool to help improve OSA. With the rising levels of obesity and OSA, an integrative care model is needed to effectively treat and prevent the metabolic and cardiovascular consequences of these epidemic diseases.

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Dr. Junaid, an allergist with a special interest in obesity, practices at Kaiser Permanente Novato.
Email: imran.x.junaid@kp.org

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