The American Diabetes Association estimates that nearly 30 million Americans live with diabetes.

Even more concerning, diabetes is the 7th leading cause of death in the U.S. The condition can be caused by an autoimmune problem, where the body attacks the cells in the pancreas that produce insulin to keep blood sugar levels in check. This is known as type 1 diabetes. Or, the condition can be type 2 diabetes which arises from insulin resistance–where the body doesn’t respond to insulin and blood sugar remains at abnormal levels. Type 2 diabetes is more common and is not an autoimmune disease but rather a “lifestyle disease” once known as adult-onset or noninsulin-dependent diabetes. There is no cure for type 2 diabetes, but it can be managed and prevented.

Type 2 diabetes is often associated with obesity, high blood pressure and heart disease, but recent research has pinpointed another condition that is linked as well: sleep apnea. 

Sleep apnea is more than just an issue with sleep quality. Sleep apnea is the interruption of breathing, typically caused when tissue in the back of the throat collapses into the airway, blocking the breath, and is associated with a host of health issues. Experts have grown certain that the disorder increases cardiovascular (heart) risk, for example. There’s also mounting evidence that sleep apnea may contribute to problems like insulin resistance, glucose intolerance and type 2 diabetes. 

“If you have hypertension (high blood pressure), you’re more likely to have obstructive sleep apnea; and if you have sleep apnea, you are more likely to have hypertension,”says Said Mostafavi, M.D., the Chief Medical Officer for Advanced Sleep Medicine Services, Inc. and a sleep specialist. “In the same way, if you have diabetes, you’re more likely to have sleep apnea; and if you have sleep apnea you’re more likely to have diabetes. So even though we don’t understand all the mechanisms, we know there is a connection between diabetes and sleep apnea. Incidence of OSA in patients with diabetes is higher than the general population regardless of BMI. Prevalence of OSA is 71% in patients with type 2 diabetes. This is significantly greater than the general population at 4-10%.”

Sleep Apnea and Diabetes are Related

Studies show that about 71% of people with diabetes may have sleep apnea. For sleep apnea to have a relationship with diabetes might come as a surprise to the general public, but physicians and scientists have noted some suggestive patterns. 

“There are many studies published during the last five to ten years showing a strong link between sleep apnea and diabetes, especially type 2 diabetes,” says Frédéric Gagnadoux, a professor of medicine at the University of Angers and a respiratory physician who specializes in sleep disordered breathing. A 2012 review of the evidence linking the two conditions estimated that about 71 percent of people with type 2 diabetes may have sleep apnea, based on an average of five studies looking at a total of 1,200 patients^1.

The link goes the other direction also.  A 2014 study looked at 6,616 people who participated in the European Sleep Apnea Cohort and looked to see how many had both sleep apnea and type 2 diabetes. 28.9% of those with severe apnea had diabetes, even when the researchers accounted for other risk factors such as obesity^2. In other words, just under a third of people with severe sleep apnea also had type 2 diabetes. 

The researchers also found that people with more severe apnea were more likely to also have type 2 diabetes: The prevalence of diabetes varied according to how severe the sleep apnea was.  The conclusion of the study reads, “Increasing OSA severity is associated with increased likelihood of concomitant T2DM (type 2 diabetes mellitus) and worse diabetic control in patients with T2DM”.

Adjusted mean HbA1c levels among diabetic subjects stratified by OSA (obstructive sleep apnea) severity

This evidence has pushed the American Academy of Sleep Medicine to advise that anyone with type 2 diabetes should get a test for sleep apnea.

 

Sleep Apnea Causes Hypoxemia and Fragmented Sleep Which May Lead to Diabetes 

Despite evidence for a strong connection between diabetes and sleep apnea, researchers still don’t know how exactly sleep apnea might lead to diabetes or if there are other underlying conditions that can cause both disorders.

The link, or part of it, may be due to the fact that sleep apnea and diabetes share some risk factors. Obesity and cardiovascular disease are related to both conditions. Sleep apnea doesn’t just increase the likelihood of developing cardiovascular disease — heart problems can also lead to sleep apnea. Also, people who have diabetes are at least twice as likely to develop heart disease, according to the National Institute of Diabetes and Digestive and Kidney Diseases. 

Obesity is another known risk factor for heart disease, but in addition, a study of 306 obese patients with diabetes found that a stunning 86 percent of them also had undiagnosed sleep apnea^3. These conditions all appear to be related. 

Experts do have some indications of what biological mechanisms might be behind this connection, based on how sleep apnea affects the body.

“There are two main consequences of sleep apnea during the night,” says Gagnadoux. He points to hypoxemia, or times when the concentration of oxygen in the blood dips to below normal levels, and sleep fragmentation. “We know from animal studies that both are risk factors for developing insulin resistance,” he adds.

Hypoxemia can set off a chain reaction in the body that leads to impaired glucose tolerance and increased oxidative stress, which means the body has an excess amount of molecules called reactive oxygen species. These molecules can disrupt the body’s ability to repair itself. The whole process can also contribute to insulin resistance.

Sleep fragmentation of any sort can push a person’s body into state of stress and cause the release of cortisol, a hormone that can strongly alter the metabolism. Repeated awakenings can also lead to insulin resistance, a greater appetite and the craving for carbohydrates. Diabetes gets its foot in the door with all these changes. Higher sleep variability has even been linked to problems with controlling the amount of glucose in the blood^4. “The more severe the apnea, the more disturbed a patient’s glucose control,” says Mostafavi.

 

CPAP Therapy Relieves Sleep Apnea and May Help Control Diabetes 

Since sleep apnea and diabetes appear to be linked, researchers have tried to determine if treating the sleep disorder might help improve a patient’s diabetes. However, studies that have examined the effect of using the gold standard for sleep apnea treatment—continuous positive airway pressure or CPAP therapy—have shown mixed results. 

On one hand, some studies have shown that CPAP therapy could improve diabetes. A 2012 study looked at 50 people with moderate to severe sleep apnea to see if CPAP could actually help control their diabetes. They gave half the participants CPAP treatment and the other half a sham CPAP for eight weeks. The team found that the therapy didn’t bring blood glucose levels back to normal completely, but it did improve insulin sensitivity in people with severe sleep apnea^5. 

In a different six month trial, 50 patients with sleep apnea and diabetes were split into a group that received CPAP and a group that did not. Measures of insulin resistance and sensitivity as well as glucose tolerance improved in the treated group, in step with better nocturnal blood oxygen levels^6. 

On the other hand, however, a study in Australia that also gave 298 people real CPAP or a placebo didn’t find improvement in blood glucose control^7. To explain their results, the Australian team wrote that “it is possible that the impact of obstructive sleep apnea is mainly relevant for the development of diabetes, but not for control of established diabetes.”

Gagnadoux’s own work has tried to detangle the reasons that CPAP may or may not help diabetes in patients who have both conditions.  He and his colleagues studied 762 people who were diagnosed with sleep apnea after their first polysomnography. The participants included 497 people already diagnosed with diabetes. The remaining 265 weren’t diagnosed with diabetes before the study, but were selected because they had elevated blood glucose levels. 

What the research team found may help explain why experts have struggled to understand if CPAP can help relieve diabetes symptoms. 

Overall, they found that people with more severe sleep apnea had lower glucose control, meaning that their blood glucose was more likely to be elevated^8. However, this pattern was not obvious in the group of people who had previously diagnosed diabetes that they were treating. “Potentially, this means that treating obstructive sleep apnea has a greater effect on blood glucose control in newly diagnosed patients,” Gagnadoux explains. Patients who are managing their diabetes already may not see improvements when they start CPAP. That doesn’t mean that CPAP therapy isn’t worth it, however.

“When you are treating a patient with both sleep apnea and diabetes, you have to treat the sleep apnea but you also have to do your best to treat the diabetes,” says Gagnadoux. Thus far, studies do not show that treating sleep apnea alone will help with diabetes. 

Still, Mostafavi advises that physicians consider CPAP therapy for sleep apnea patients, but especially for those who have both sleep apnea and diabetes. “The data on CPAP treatment and glucose controls is mixed, I can’t claim that putting people on CPAP is going to make their diabetes go away,” he says. “Some do see an improvement, some don’t. But sleep apnea is a significant condition in itself that requires treatment.”

 

As Research Continues, It’s Clear That Doctors Should Talk to Their Diabetes Patients About Sleep

Even if experts don’t understand the exact mechanism driving the relationship between diabetes and sleep apnea, they do know it exists. Furthermore, the connection is strong enough, and the effects of leaving either condition untreated are dangerous enough, that physicians should seriously consider asking their patients with diabetes about their sleep quality. 

Mostafavi advises his fellow physicians to get a good history from their patients. “If you have an overweight patient ask them if they snore, or if their partner complains of sleep noise. Also ask if they are sleepy — that is the hallmark of sleep apnea: daytime sleepiness,” he says. But also make sure to ask the bed partner. “The best and more reliable history always comes from the bed partner and the most unreliable history comes from the patient.  A sleeper is deaf to their own snores, but if their partner complains, you can believe them.” 

Whether further research supports the idea that CPAP therapy could help with diabetes control or not, treating both conditions when they occur is paramount. To ignore either certainly won’t help. 

“The upside of treating sleep apnea alone is enough and the downside of treating it in a patient who also has diabetes is nothing,” Mostafavi says.

 

If some of the hints in these studies hold up under further investigation, CPAP may not just lead to better sleep. The therapy could help with diabetes management. If you have patients, ask them if they snore and talk to their bed partner. If you’d like a tool for assessing your patients’ sleepiness, download this Epworth Sleepiness Scale:

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인용된 연구:

1. Pamidi, S. & E. Tasali, (2012). Obstructive Sleep Apnea and Type 2 Diabetes: Is There a Link?. Front Neurol, 3(126), eCollection. PubMed
2. Kent, B.D., et al., (2014). Diabetes mellitus prevalence and control in sleep-disordered breathing: the European Sleep Apnea Cohort (ESADA) study. Chest, 146(4), 982-990. PubMed 
3. Foster, G.D. et al., (2009). Obstructive Sleep Apnea Among Obese Patients with Type 2 Diabetes. Diabetes Care, 32(6), 1017-1019. PubMed
4. Tachikawa R. et al., (2016). Higher Sleep Variability is Associated with Poorer Glycaemic Control in Patients with Type 1 Diabetes. Am J Respir Crit Care Med, [Epub ahead of print]. PubMed
5. Weinstock T.G. et al., (2012). A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea. Sleep, 35(5), 617-625B. PubMed 
6. Martínez-Cerón E. et al., (2016). Effect of CPAP on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial. Am J Respir Crit Care Med. [epub ahead of print]. 
7. Shaw J.E. et al., (2016). The Effect of Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes. Am J Respir Crit Care Med, [Epub ahead of print]. PubMed 
8. Priou T. et al, (2015). Association Between Obstructive Sleep Apnea Severity and Glucose Control in Patients with Untreated Versus Treated Diabetes. J Sleep Res, 24(4), 425-431. PubMed