Expert Blog

Sleep Apnea in Patients with Type 2 Diabetes

Doron Schneider, MD, FACP
General Internist
Obstructive sleep apnea (OSA) is a common and underdiagnosed condition in patients with type 2 diabetes (T2DM).1 Characteristic features include habitual snoring, witnessed apnea, and excessive daytime sleepiness, often with associated fatigue and energy loss, irritability, poor memory, depression, personality change, morning headaches, sexual dysfunction, and nocturia. More recently sleep apnea has been linked with hypertension, metabolic syndrome, cardiovascular diseases, and arrhythmias as well as type 2 diabetes.2 This blog post explores what is known about the underlying mechanism that may relate sleep apnea to diabetes. Has an underlying pathophysiologic mechanism been elucidated that brings clarity to these relationship?  If so, is it causal?  Or are both conditions observed in individuals but have no interrelationship?  So here goes….

While the association between OSA and the development of prediabetes, the metabolic syndrome, and frank diabetes is now well appreciated, the underlying mechanism of this association is several fold. In Medical Hypotheses,
3 Pallayova et al. propose a causal relationship between sleep apnea and diabetes. Drawing on previous research, the group suggests that sleep apnea imposes an excessive demand for insulin/glucose metabolism that in susceptible individuals may lead to progressive beta cell failure. The mechanism for this increased beta cell demand is thought to be ongoing intermittent episodes of hypoxia causing excessive autonomic nervous system activation. This hypoxia may also alter gene expression for pancreatic synthesis of key enzymes, such as pancreatic proinsulin convertases, that may be additional factors altering glucose homeostatis.

The research upon which this hypothesis drew found that, in severely obese patients with either prediabetes or diabetes, increasing severity of sleep apnea (defined as an increasing apnea hypopnea index) was associated with reductions in HOMA-IS (a measurement of insulin sensitivity). In obese patients with normal glucose metabolism, increased sleep apnea severity was associated with significantly increased HOMA-B levels (a marker of beta cell function). By extrapolation, increased HOMA-B in obese patients with sleep apnea demonstrates increased beta cell demand. Hypoxia was found to also increase inflammatory biomarkers TNF-alpha and IL-6 in patients with sleep apnea and normal glucose metabolism, suggesting the beta-cell-mediated stress in obesity prior to onset of prediabetes or diabetes is related to inflammation.
4

A growing consensus is emerging that acknowledges both increased beta cell demand in OSA as well as increased insulin resistance. In one of several trials to show the association of OSA and sleep apnea, Punjab et al., studying over 2,000 participants in the Sleep Heart Health Study, found that participants with moderate to severe sleep-disordered breathing had higher HOMA-IR values, indicating an insulin resistant state. This association was independent of
age, gender, ethnicity, smoking status, body mass index, waist circumference, and sleep duration.5

Although early studies using CPAP or BIPAP to correct OSA showed no impact on diabetes risk, more recent investigations suggest that CPAP may indeed be helpful in improving glucose homeostasis. Lindberg et al., for example, found improvements in insulin levels and insulin resistance as defined by HOMA after 3 weeks of CPAP treatment in 28 men with OSA in comparison to age-matched controls without OSA.
6 

These findings suggest that treating OSA in obese patients who have normal glucose metabolism may be important in delaying or stopping diabetes progression. To reduce the burden of secondary illnesses, including T2DM, practitioners should have a low threshold for sending patients for sleep studies.


RESOURCES


1 West SD, Nicoll DJ, Stradling JR. Prevalence of obstructive sleep apnoea in men with type 2 diabetes. Thorax 2006;61(11):945-950.

2 Shaw JE, Punjabi NM, Wilding JP, et al. Sleep-disordered breathing and type 2 diabetes: A report from the International Diabetes Federation Taskforce on Epidemiology and Prevention. Diabetes Research and Clinical Practice 2008;81:2-12.

3 Pallayova M, Lazurova I, Donic V. Hypoxic damage to pancreatic beta cells—The hidden link between sleep apnea and diabetes. Medical Hypotheses 2011;77(5):930-934.

4 Pallayova M, Steele KE, Magnuson TH, et al. Sleep apnea predicts distinct alterations in glucose homeostasis in obese adults with normal and impaired glucose metabolism. Cardiovasc Diabetol 2010;9:83. See also Wang N, Khan SA, Prabhaker NR, et al. Impairment of pancreatic β-cell function by chronic intermittent hypoxia. Exp Physiol 2013;98(9):1376-1385.

5 Punjabi NM, Shahar E, Redline S, et al. Sleep-disordered breathing, glucose intolerance, and insulin resistance. J Epidemiol 2004;160:521-530.

6 Lindberg E, Berne C, Elmasry A, et al. CPAP treatment of a population-based sample: What are the benefits and the treatment compliance? Sleep Med 2006;7:553–560.

 

 

Comments

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