Be alert for sleep disorders in Type 2 diabetes

Diabetes and sleep are intricately connected. It is estimated that one of two people with type 2 diabetes has sleep issues, presenting as either poor quality of sleep or insomnia.1 Despite this high prevalence, sleep problems in those living with type 2 diabetes may not be well-recognized or addressed. In fact, a recent systematic review found that few diabetes clinical practice guidelines provide recommendations for assessment and management of sleep in this patient population.2 Pharmacists have the opportunity to play an important role in identifying and helping to manage sleep disturbances in patients with type 2 diabetes. A recent review identified that 25% of people with diabetes get less than six hours or more than eight hours of sleep a night.3 The relationship between duration of sleep and glycated hemoglobin (A1C) values in patients with type 2 diabetes follows a U-shaped curve, with worse A1C values in those who sleep shorter or longer durations than seven to eight hours per night.4 A bi-directional relationship exists between type 2 diabetes and sleep. Diabetes itself can cause sleep problems, and conversely, sleep problems also appear to play a role in diabetes, as discussed in this column. Diabetes-related causes for sleep disturbances Both hyperglycemia and hypoglycemia during the night can lead to insomnia and next-day fatigue. In addition, living with a chronic disease, such as diabetes, has a significant emotional toll, with potential to further interrupt sleep patterns. Hyperglycemia High blood glucose levels can result in increased urinary frequency, requiring more bathroom trips during the night, and thereby disrupting sleep. A rapid eye movement (REM) latency period (i.e., the time from sleep onset to the first period of REM sleep) that is shorter or longer than usual may be caused by sleep deprivation or sleep disorders. Higher A1C levels have been shown to be significantly associated with a reduction of REM sleep latency in people with type 2 diabetes. This suggests that poor glycemic control may be associated with impairment of sleep quality through shortening the most important, deepest sleep cycle.5 Hypoglycemia Symptoms of hypoglycemia can include sweating, irritation and confusion, which can also cause interruptions in sleep. Depression Individuals with diabetes also have a significantly increased risk of developing depression compared to their counterparts without diabetes. Depression is one of the important factors contributing to poor sleep in the diabetes population.6 Sleep disturbances causing diabetes Poor sleep or less restorative slow-wave sleep is linked to high blood glucose levels in people with diabetes or prediabetes.5 It is thought that sleep disturbances may affect blood glucose levels due to their effect on insulin, cortisol and oxidative stress.7 Sleep deprivation can also raise the risk of developing insulin resistance, even as early as childhood.8 Types of sleep disorders in type 2 diabetes Obstructive sleep apnea and restless legs syndrome are the two most common sleep disorders in people with type 2 diabetes. Although sleep apnea does not directly cause diabetes, it is a risk factor for diabetes and has been shown to increase insulin resistance, even in people without diabetes or who are not overweight.9 Obstructive sleep apnea is characterized by episodes of partial or complete upper airway collapse (apnea) during sleep, leading to hypoxemia and sleep fragmentation.10 The lapses in breathing cause ‘micro-arousals’ (very brief awakenings) that interfere with the natural progression of the sleep stages and impair sleep quality. Symptoms may include loud snoring, choking and gasping episodes, waking up sweating during sleep, feeling unrefreshed in the morning, morning headaches and excessive daytime sleepiness and lethargy. Usually, the person is unaware of their nighttime symptoms. Obstructive sleep apnea occurs more frequently in people who are overweight or obese, as excess fat in the neck (signified by a neck circumference > 16 inches in women or > 17 inches in men) interferes with the airway. Sleep apnea has also received increased attention in the past decade due to its independent associations with cardiovascular diseases.10 A polysomnogram, or sleep study, may be recommended to initially diagnose obstructive sleep apnea. Treatment includes the use of a continuous positive airway pressure (CPAP) device. CPAP keeps the airway open, helping to restore normal breathing, and subsequently normal sleep patterns.11 People with restless legs syndrome (RLS) may feel tingling or other irritating sensations in the legs, leading to an uncontrollable urge to move their legs that can interfere with getting to sleep. Symptoms of peripheral neuropathy, a common complication in people with type 2 diabetes, can be similar to those of RLS, including numbness, tingling and pain in the extremities. Neuropathic symptoms differ from RLS symptoms in that they are not usually associated with motor restlessness or helped by movement. They also can occur during the day or night, whereas RLS symptoms typically occur during the evening or night. Neuropathy and RLS can coexist in someone living with diabetes.12 People with RLS should be tested for iron deficiency. Drug therapy for primary RLS is largely symptomatic and may include dopaminergic agents, benzodiazepines, anticonvulsants or iron salts. Treatment may not be necessary for patients with mild or sporadic symptoms or for those without significant impairment.13 How to improve sleep quality For those diagnosed with obstructive sleep apnea, a combination of weight loss and CPAP treatment may be the most effective method to improve sleep patterns and subsequently improve insulin resistance and impaired glucose metabolism.14 Good sleep hygiene habits are particularly important and can include: • Adhering to a diet plan that works to help control blood glucose levels • Getting regular exercise • Keeping a regular bedtime and rise time • Avoiding stimulants (e.g., caffeine, nicotine) before bed • Keeping the bedroom cool, dark and quiet • Putting cell phones and other devices in silent/off mode.15 Management of insomnia Cognitive behavioural therapy (CBT) is recommended as first-line treatment for chronic insomnia. CBT is not always highly accessible and can be expensive, and patient response may be poor in some instances. Pharmacologic management is therefore commonly used. Side effects and a narrow therapeutic index limit use of some of the older medications. Newer pharmacologic options have demonstrated a better safety profile and longer-term efficacy. Evidence is conflicting related to adverse outcomes with long-term treatment; therefore, medication use should always be individualized. It is important to consider the potential risks of continuing hypnotic medication with the risks of untreated persistent insomnia and its associated functional limitations.16 How to help patients living with diabetes and sleep disorders Since excessive daytime sleepiness can be detrimental to mood and job performance, and increase the risk of occupational injuries and transportation-related accidents, assessment of sleep quality and sleep disorders is of paramount importance in persons living with type 2 diabetes. How can you make a difference? • Advise patients to speak with their diabetes care team to determine if they require treatment for symptoms of RLS or peripheral neuropathy. • Suggest a sleep study if obstructive sleep apnea is a possibility, especially in patients who are overweight or obese. If applicable, include the patient’s partner, for identifying nighttime symptoms. • Refer all patients with sleep disturbances for an evaluation for depression. • Recommend good sleep hygiene habits (discussed above) and, if necessary, refer for assessment for additional behavioural approaches (e.g., CBT, relaxation therapies). • Consider short-term pharmacotherapy as an adjunct to cognitive and behavioural therapies for insomnia, if needed. • Disturbed sleep patterns may cause people with diabetes to be less likely to follow recommended diabetes self-management practices, such as regular exercise and monitoring of blood glucose levels. Help patients get ‘back on track’ by setting one goal at a time. This is important and should coincide with your assessment of how best to support or refer for sleep disorders. Summary Successful management of sleep disorders in patients with type 2 diabetes often requires a multifaceted approach including relief of symptoms and treatment of common comorbid conditions. Work with your patients and their healthcare providers to improve sleep patterns. A good sleep is essential to everyone’s health and well-being! Shelley Diamond, BScPhm, is a pharmacist and co-founder of www.diabetescarecommunity.ca, an extensive online resource for Canadians living with diabetes, their families and healthcare professionals. References: 1. Zhu B, Quinn L, Kapella MC, et al. Relationship between sleep disturbance and self-care in adults with type 2 diabetes. Acta Diabetol 2018;55:963-70. 2. Smyth A, Jenkins M, Dunham M, et al. Systematic review of clinical practice guidelines to identify recommendations for sleep in type 2 diabetes mellitus management. Diabetes Res Clin Pract 2020;170:108532. https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30789-0/fulltext (accessed March 22, 2022). 3. Brouwer A, van Raalte DH, Rutters F, et al. Sleep and HbA1C in patients with type 2 diabetes: which sleep characteristics matter most? Diabetes Care 2020;43:235-43. 4. Lee SWH, Ng KY, Chin WK. The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: a systematic review and meta-analysis. Sleep Med Rev 2017;31:91-101. 5. Yoda K, Inaba M, Hamamoto K, et al. Association between poor glycemic control, impaired sleep quality, and increased arterial thickening in type 2 diabetic patients. PLoS One 2015;10(4):e0122521. 6. Zhang P, Lou P, Chang G, et al. Combined effects of sleep quality and depression on quality of life in patients with type 2 diabetes. BMC Family Practice 2016;17(40). DOI 10.1186/s12875-016-0435-x. 7. Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 2011;50:567-75. 8. Dutil C, Chaput JP. Inadequate sleep as a contributor to type 2 diabetes in children and adolescents. Nutr Diabetes 2017;7(5):e266. 9. Kritikou I, Basta M, Vgoontzas AN, et al. Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females. Eur Respir J 2014;43:145-55. 10. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council and Council on Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Centre on Sleep Disorders Research (National Institute of Health). Circulation 2008;118:1080-111. 11. Laratta C, Ayas N, Povitz M, et al. Diagnosis and treatment of obstructive sleep apnea in adults. CMAJ 2017;189:E1481-8. 12. Kalra S, Gupta A. Diabetic painful neuropathy and restless legs syndrome in diabetes. Diabetes Ther 2018;9(2):441-7. 13. Bozorg A. Restless legs syndrome treatment and management. Medscape; January 6, 2022. https://emedicine.medscape.com/article/1188327-treatment#d10 (accessed March 17, 2022). 14. Kuna ST, Reboussin DM, Borradaile KE, et al. Long-term effect of weight loss on obstructive sleep apnea severity in obese patients with type 2 diabetes. Sleep 2013;36(5):641-649A. 15. American Academy of Sleep Medicine. Healthy sleep habits. https://sleepeducation.org/healthy-sleep/healthy-sleep-habits/ (accessed March 17, 2022). 16. Madari S, Golebiowski R, Mansukhani M, et al. Pharmacological management of insomnia. Neurotherapeutics 2021;18(1):44-52.

Be alert for sleep disorders in Type 2 diabetes

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Shelley Diamond