The Link Between Obstructive Sleep Apnea and Type 2 Diabetes Mellitus

Obstructive sleep apnea (OSA) is a treatable chronic sleep disorder characterized by recurrent episodes of complete (apnea) or partial (hypopnea) obstruction of the upper airway. This leads to intermittent hypoxemia and hypercapnia, micro-awakenings, increased oxidative stress, inflammation, and sleep fragmentation. Clinical correlates of disturbed sleep include excessive daytime sleepiness, poor work/school performance, and reduced quality of life. The apnea hypopnea index (AHI), which is the number of apneas and hypopneas per hour of sleep, helps define the severity of OSA. An AHI of 5-15 is mild, 15-30 is moderate, and >30 is severe. It should be noted that the symptoms of sleep apnea such as excessive sleepiness and sleep disruption may be present and pronounced in even mild cases or may be absent in severe OSA.1

Obesity and type 2 diabetes are commonly seen in OSA so it is not surprising that OSA rates along with obesity and type 2 diabetes are expected to increase in the future. Studies reveal an incidence rate of 15% to 30% of OSA in persons with type 2 diabetes and most of these are severe.2-5 Despite the close correlation between type 2 diabetes and OSA, many cases are not detected. In a retrospective, multi-site, population-based study of over 16,000 patients with diabetes, primary care clinicians diagnosed only 18% with OSA which is much lower than expected in this population.6 With recent advances and availability of home sleep apnea testing, primary care providers are in a position to help facilitate the diagnosis and treatment of OSA. However, awareness of the pitfalls of diagnosis and treatment options is required to ensure proper identification and successful management of patients with sleep apnea.

Pathophysiology

Although epidemiological studies note an association between OSA and type 2 diabetes, the physiologic mechanism is unclear. Neuroendocrine mediated physiologic changes have been proposed as possible contributors to the link between diabetes and OSA. This may occur through alterations in the metabolism of glucose and fatty acids. Clinically, poor glycemic control in patients with OSA may be associated with disturbances in sleep patterns. OSA-induced cyclic hypoxia, sleep restriction and sleep fragmentation have been shown to cause sympathetic overdrive, oxidative bursts and chronic increases in pro-inflammatory cytokines. These metabolic changes can activate the hypothalamic — pituitary — adrenal axis and alter circulating adipokines. The result of these changes may lead to an increase in appetite and obesity, which could cause increased insulin resistance as well as possible dysfunction and destruction of the pancreatic beta cells. It is a vicious cycle, where type 2 diabetes is an independent risk factor for OSA, and OSA can be associated with worsening glucose control.7

Men demonstrating sleep study equipment
Examples of a Home Sleep Apnea Test (HSAT) (left) and Polysomnography (PSG) (right)

Making the diagnosis of OSA

The diagnosis of OSA in primary care may start with a validated questionnaire such as the STOP-Bang questionnaire, which uses the presence of Snoring, Tiredness, Observed apneas, high blood Pressure, Body mass index>35 kg/m2, Age>50, Neck size and Gender to identify high-risk patients for OSA. Since these questionnaires have significant false negative and false positive rates, they are not recommended as the sole tool for diagnosis of OSA.8

Ultimately, the diagnosis of OSA must be confirmed with a sleep study prior to initiating treatment. There are two general types of sleep tests commonly used to diagnose OSA: the Home Sleep Apnea Test (HSAT) and the more traditional polysomnography (PSG). The HSAT is a limited-channel study that most commonly measures nasal flow, respiratory effort, heart rate and oxygen saturation and is often performed in the patient’s home. In contrast to the HSAT, a PSG is generally performed in a sleep center and contains EEG signals to determine the presence of sleep stages and arousals in addition to the channels contained in the HSAT. PSG is more expensive than HSAT, and PSG accessibility may be limited in some geographic areas. In patients at high risk for OSA, studies demonstrate that treatment outcomes and adherence are not statistically different between subjects diagnosed with HSAT or PSG. Current guidelines recommend that polysomnography or home sleep apnea testing with a technically adequate device be used for the diagnosis of OSA in uncomplicated adult patients presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA.8 On a practical level, the patient’s insurance coverage may be the major determinant for which test is utilized. The presence of diabetes is generally not a major factor in deciding which diagnostic test to use. If a clinician uses a HSAT to diagnose OSA, there are some important caveats that must be appreciated. In patients with significant cardiorespiratory disease, potential respiratory muscle weakness due to neuromuscular conditions, awake hypoventilation or suspicion of sleep-related hypoventilation, chronic opioid medication use, history of stroke or severe insomnia, a PSG is recommended over an HSAT. Additionally, there is up to an 18% false negative rate for HSAT in high-risk patients, so if a single HSAT is negative, inconclusive, or technically inadequate, a PSG should be performed.8,9

Treatment of OSA

Nasal continuous positive airway pressure (CPAP) is the most effective treatment for OSA. CPAP is the standard therapy for patients with moderate-to-severe OSA and can effectively improve daytime alertness, functional status, blood pressure, and quality of life.10-11 A CPAP machine provides air pressure during sleep that stents open the airway and prevents obstruction leading to OSA. While there are numerous CPAP masks available, a nasal interface is recommended over a full face mask due to improved comfort and adherence to treatment.11 Often, an auto-titrating CPAP machine (APAP) is prescribed. Unlike traditional CPAP which is set to deliver one continuous pressure, auto-titrating CPAP provides pressure within a range, usually 6 to 20 cmH20, and uses algorithm technology that adjusts pressure based on the patients breathing. In the past, patients would need to have a CPAP titration sleep study to fine tune the therapeutic CPAP pressure. For many patients, this is no longer necessary due to auto-titrating CPAP technology. Additionally, most current CPAP units have the capability to monitor machine usage, residual sleep apnea and mask fit. This information is available to clinicians through a cloud-based software platform. Additionally, some CPAP units can connect with the patient’s smart phone via an app to provide similar data.

While CPAP is the most common treatment for OSA, there are additional therapeutic options. Oral appliance therapy (mandibular advancement dental appliance) works by moving the lower jaw forward. Oral appliances are recommended for the treatment of mild to moderate OSA and are generally covered by many commercial medical insurers and Medicare. They can be used as first-line treatment or in patients who cannot tolerate CPAP.12

Effect of OSA on type 2 diabetes

Since OSA and type 2 diabetes are associated, one might expect that CPAP therapy could improve glycemic control. Study results on this have been mixed. CPAP does effectively reduce insulin resistance.13-15 However, it may not improve hemoglobin A1c (A1C) or fasting plasma glucose.16 The effect of CPAP treatment on weight is also unclear. In one trial, CPAP was unexpectedly associated with modest weight gain in the treatment group.16

The beneficial effect of CPAP therapy depends on patient adherence and time using the device. When used for greater than four hours per night, CPAP lowers blood pressure and subjective daytime sleepiness.11 Some recent data suggest that longer use of CPAP (at least eight hours per night) may yield metabolic benefits. One study with a supervised, eight-hour per night of CPAP therapy in prediabetes patients showed a significant decrease in overall glucose response with oral and intravenous glucose tolerance tests.14 Therefore, CPAP usage should be monitored by the clinician, and if patients experience problems with using CPAP, they should be referred to a sleep medicine specialist for evaluation and further management.

In summary, it is important for primary care clinicians to be aware of the high incidence of OSA in persons with type 2 diabetes and to understand how to diagnose and treat OSA including pitfalls with home testing. Although it is not clear if management of OSA improves glycemic control, emerging data suggest that longer use of CPAP (eight hours per night) may potentially yield metabolic benefits. Cloud-based and smart phone compatible apps can track CPAP use and may be key to aid adherence with OSA treatment.

Takeaway points

1. OSA is common in patients with type 2 diabetes and primary care clinicians can play an important role in identifying patients.

2. Home sleep apnea testing (HSAT) is not appropriate for all patients who have suspected OSA and a negative result should prompt further evaluation or testing, especially in high risk patients.

3. Advances in CPAP technology now allow patients and clinicians to monitor CPAP nightly usage and effectiveness.

4. For those who cannot tolerate or accept CPAP, alternative treatments do exist, most notably oral appliance therapy.

Access additional resources and practical information to enhance the care and treatment of your diabetes patients.

About our experts

Ali ErshadiAli Ershadi, MD, Norwalk Hospital, Western Connecticut Health Network, Norwalk, Connecticut

 

 

 

 

Ian WeirIan D. Weir, DO, Norwalk Hospital, Clinical Instructor of Medicine, Yale School of Medicine, New Haven, Connecticut, Adjunct Assistant Professor of Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont, Adjunct Assistant Professor of Medicine, Ross University School of Medicine, Barbados, West Indies

 

 

Nancy RennertNancy J. Rennert, MD, Norwalk Hospital, Associate Clinical Professor of Medicine, Yale School of Medicine, New Haven, Connecticut, Associate Clinical Professor of Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont

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