Research & Education

Sleep Apnea and Metabolic Dysfunction – a Two-Way Street?


We take it for granted that obesity is a risk factor for sleep apnea. Excess body weight particularly around the midsection may make it difficult for some people to breathe properly in a supine position. But what if the association between obesity and sleep apnea was a two-way street and an obstructed airway during slumber was a risk factor for weight gain? A pretty robust amount of research indicates this might be the case with one of the underlying culprits being—surprise surprise—elevated insulin. 

According to one study “Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.” (Indeed adipose tissue dysfunction is a little-known but perhaps major player in the etiology of type 2 diabetes so anything that contributes to dysfunctional adipose—such as hypoxia from OSA—could potentially lead to insulin resistance over the long term.) Under this type of paradigm even if obesity does make an unobstructed airway more difficult to maintain during sleep we must ask what’s causing the obesity in the first place.

Of course there are a multitude of factors that lead to obesity but chronic hyperinsulinemia is an obvious and underappreciated one. This makes it difficult to tease out whether elevated insulin is the cart or the horse as they say. Either way it’s a vicious cycle. Too many patients with OSA are told to lose weight—as if becoming leaner will magically keep their airway open—but they’re given little useful guidance on how to do this.

In a small study of patients with moderate to severe OSA who were habitual users of a continuous positive airway pressure (CPAP) machine when CPAP treatment was stopped the patients had higher nocturnal levels of free fatty acids glucose and cortisol “in proportion to respiratory event frequency heart rate elevation or sleep fragmentation.” The researchers wrote this powerful conclusion: “OSA recurrence during CPAP withdrawal increases FFA and glucose during sleep associated with sympathetic and adrenocortical activation. Recurring exposure to these metabolic changes may foster diabetes and cardiovascular disease.”

Other researchers have similar thoughts. They note that intermittent hypoxia (IH) could potentially “induce dyslipidemia by up-regulating lipid biosynthesis in the liver increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation increasing systemic inflammation increasing counter-regulatory hormones and fatty acids and causing direct pancreatic beta-cell injury.” Certainly dietary and lifestyle choices play a large role in metabolic health but no one chooses sleep apnea. Patients who struggle to normalize their glycemic control or lipids even while following a good diet and exercise program should be evaluated for sleep apnea if they report other signs and symptoms of chronically disturbed sleep.

Type 2 diabetes OSA and obesity have all increased in incidence. It’s easy to blame the former two on the latter as some researchers do but they also acknowledge “the confounding effect of obesity complicates the establishment of a causal relationship between OSA and insulin resistance.” Other researchers note “Obesity predisposes to OSA and the prevalence of OSA is increasing worldwide because of the ongoing epidemic of obesity.” Here they lay the blame for OSA squarely on obesity never mind that plenty of people with OSA are not obese. They go on to say “findings from animal models and patients with OSA show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity augmenting insulin resistance and nonalcoholic fatty liver disease.” Does IH merely exacerbate and augment these or could it actually be a causal factor? It’s possible that many medical professionals are still wedded to the notion that a high body weight can only be a cause of cardiometabolic problems rather than yet one more result of an underlying hormonal disturbance that leads to metabolic dysfunction and obesity. Even those who witness medical issues in people of all shapes and sizes may find it difficult not to jump to conclusions based solely on someone’s body weight.

Does obesity cause insulin resistance and OSA or could OSA be contributing to insulin resistance and thus obesity? Again with such a tangled web weaving these issues together it’s hard to tease out which is the causal factor—or maybe there isn’t a single one but rather it’s their influences on each other. For example women with PCOS have a high prevalence of sleep apnea. Or might it be more apt to say that women with sleep apnea are at greater risk for PCOS owing to disturbed insulin signaling/metabolic syndrome?

Studies are mixed with regard to the influence of CPAP usage and improvements in glycemic control and insulin resistance. In non-diabetic patients with newly diagnosed OSA 6 months of CPAP usage significantly reduced HbA1c but had no effect on markers of insulin resistance. (However groups were split into those with an average CPAP use of 4 hours per night or an average of less than 4 hours per night. Perhaps results would have been more impressive if the machines had been employed for a longer period each night.) In a different study patients with prediabetes and OSA who used a CPAP for 8 hours per night showed reductions in glucose response and norepinephrine levels and improvement in insulin sensitivity. As other researchers have noted it may be that CPAP use is more beneficial for those who are already diabetic or pre-diabetic: “it seems possible that the effect of CPAP is still greater in patients with OSA and T2DM particularly in those patients with more severe and symptomatic OSA in those with poorer baseline glycemic control and with greater compliance and duration of CPAP treatment.”

The direction of causality remains to be determined between OSA obesity and metabolic dysfunction but one thing we do know is that people of all sizes deserve what many of us take for granted: a good night’s sleep.