Obstructive sleep apnea and the metabolic syndrome: The road to clinically-meaningful phenotyping, improved prognosis, and personalized treatment

Abstract

Summary Obstructive sleep apnea (OSA) is an increasingly prevalent sleep disorder characterized by upper airway obstruction during sleep, resulting in breathing pauses, intermittent hypoxia, and fragmented sleep. In parallel, the constellation of adverse health outcomes associated with prolonged obesity, such as insulin resistance, elevated blood pressure, triglycerides, and reduced high-density lipoprotein cholesterol – termed metabolic syndrome –raises the risk of cardiovascular morbidity and mortality, type 2 diabetes, and all-cause mortality. Affecting 35–40% of U.S. adults, risk factors for metabolic syndrome, including obesity, middle age, sedentary behavior, and genetics, share considerable overlap with those for OSA. Thus, it has been difficult to disentangle cause, effect, and whether certain treatments, such as CPAP, can improve these outcomes. In this paper, we provide an update to our 2005 review which explored the association between OSA and metabolic syndrome, highlighting visceral obesity as the common etiological factor of both conditions. This update includes (a) recent data on physiological and biochemical mechanisms, (b) new data in nonobese men and women as well as children and adolescents, (c) insight from the latest treatment studies, (d) the role of aging in understanding clinically-meaningful phenotypes of the disorder, and (e) the potential diagnostic/prognostic utility of biomarkers in identifying OSA patients with the strongest cardiometabolic risk.

Adipose tissue as a key player in obstructive sleep apnoea

“…Adipose tissue, ectopic fat and lipids in OSA: insights from clinical studies OSA is independently associated with the different components of the metabolic syndrome, particularly visceral obesity, hypertension, insulin resistance and abnormal lipid metabolism [46]. There is a bidirectional relationship between OSA, adipose tissue/obesity and metabolic diseases.…”

Prevalence of undiagnosed glucose intolerance and type 2 diabetes in patients with moderate-to-severe obstructive sleep apnea syndrome

“…Pathophysiological links between OSAS and DM are bidirectional. Risk factors are similar: middle age, sedentary behavior, poor diet, and genetics [28]. Visceral obesity is associated with fat accumulation in the neck and with high levels of CRP and IL-6, both risk factors for OSAS [29].…”

Short Telomere Length and Endophenotypes in Sleep Medicine

“…Based on these data it has been proposed that OSA in the young and middle-aged is a different phenotype than in older adults. 20 It is possible that the loss of the association after controlling for age between OSA and short telomere length in the study by Tempaku et al is likely due to the high prevalence of OSA in the older group given that this was a study in a general population sample. Another potential factor may be central obesity, particularly in the association of moderate-to-severe OSA with short telomere length in young and middle-aged adults.…”

“…It is well-established that obesity, particularly central/visceral adiposity, is the strongest risk factor for OSA and tightly associated with cardiometabolic morbidity. 20 Furthermore, age appears to modify significantly the association of OSA with morbidity and mortality. Although the prevalence of OSA, defined solely by AHI criteria, increases linearly with age, its severity tends to diminish with age.…”