Sleeping away diabetic complications

Sleep should occupy 25% to 33% of our 24-hour day, and most people would like to maximize this peaceful and relaxing time. No one has figured out why we need to sleep, although many hypotheses have been put forward. We do know, however, that if the quantity and quality of our sleep are not good, we don’t feel well the next day. In the last several years, research has shown that poor quality and/or quantity of sleep can lead to problems with memory and cognition, weight gain, hypertension, diabetes, atherogenic dyslipidemia, stroke, and myocardial infarction.

Sleep complaints are very common in the diabetic patient. For example, patients with Type 2 diabetes have higher rates of insomnia than nondiabetic people, and often this is associated with other complications, such as restless legs syndrome (1). The Sleep Heart Health Study reported that diabetes is often associated with both obstructive and central sleep apnea (2). This paper discusses insomnia and sleep apnea, their respective impacts on diabetes and related diseases, and their treatments.

Consequences of Insomnia

Insomnia affects 33% of our population at some point during their lifetime and has been associated with several diseases. Multiple studies (3, 4) have consistently shown a U-shaped curve relating sleep time to the development and/or worsening of diabetes, metabolic syndrome, and hypertension. Individuals who get fewer than 6 hours or more than 8 hours of sleep per night develop these three conditions much more often than individuals who sleep 7–7.5 hours per night.

Short sleep duration, therefore, may be a significant risk factor for diabetes (5). The mechanism proposed is an increase in activity of the sympathetic nervous system that raises evening cortisol levels and decreases cerebral glucose utilization, leading to insulin resistance and later to diabetes. Chronic sleep deprivation is thought to decrease leptin levels and increase ghrelin levels, leading to increased hunger and weight gain. Poor sleep maintenance (i.e., frequent micro-arousals) that suppresses slow-wave sleep is thought to cause a decrease in insulin sensitivity and an increase in daytime sympathetic activity (6). Long sleep duration (>8 hours) has also been associated with diabetes, but the mechanisms have not been clarified. Poor sleep duration—both too short and too long—may also affect the suprachiasmic nucleus, which organizes the autonomic rhythms of the body.

Like diabetes, metabolic syndrome has been associated with both short and long sleep duration. The odds of developing metabolic syndrome were found to increase by more than 45% in short and long sleepers as compared with individuals who slept 7–8 hours per night (7). One component of metabolic syndrome, hypertension, has been associated with sleeping less than 5 hours per night (8).These poor sleepers were also at least 1.6 times more likely to meet the criteria for abdominal obesity. Another U-shaped association was found between sleep duration and both high triglycerides and low levels of high-density lipoprotein cholesterol among women, but not men (9). Considering this information, it is not surprising that carotid intima-media thickness was reportedly greater among those with short or long sleep duration (10).

Sleep disturbances have been associated with other types of morbidity and even mortality. Shift workers, who are typically short sleepers, have been found to have more diseases than non-shift workers. The World Health Organization’s International Agency for Research on Cancer and the National Cancer Institute implicated the graveyard shift as a “probable”cause of cancer, based on higher incidence of breast cancer and prostate cancer among women and men who work during the night(11). Finally, the Whitehall II cohort study was“the first study to show that both a decrease in sleep duration and an increase in sleep duration are associated with an increase in mortality via effects on cardiovascular death and non-cardiovascular death respectively” (12).

Treatment of Insomnia

The treatment prescribed by non–sleep professionals has been very inconsistent and can be harmful to patients. Insomnia is best treated with a combination of behavioral therapy and medication. In my experience during 25 years of sleep-medicine work, I have found that the need for sleep medication decreases as proper sleep hygiene increases. Ledet’s Four Cardinal Rules of Insomnia Management, described below, combine many behavioral modalities that have proved useful when dealing with insomnia patients. These and other sleep-hygiene measures are given to patients in written form before they leave their first office visit.

Cardinal rule 1. Patients should wake up at the same time each morning (while allowing 30 minutes longer on weekends). This is very important to keep the sleep–wake cycle consistent.

Cardinal rule 2. Eight hours before wake-uptime is bedroom time, but not yet bedtime. Persons with insomnia must prepare for sleep in order to avoid “fearing bedtime.” I recommend that after bathroom time, the patient sit in a chair next to the bed, not in the bed, in order to “take your foot off the accelerator and put it on the brake.” In other words, this practice should stop the brain’s racing thoughts (accelerator) and teach the brain that it is time to stop working (brake). Sometimes it helps the patient to write down these racing thoughts to train the brain to save them until the morning. Next, it is time to turn off the lights and relax with music, meditation, and/or prayer. Only after becoming sleepy should the patient get into bed. Sleep medications, ifneeded, can be taken at this time. The only over-the-counter sleep medication I allow is melatonin, if it helps. Other over-the-counter medications simply disrupt sleep quantity and quality and eventually cause worsening insomnia, weight gain, loss of memory, and poor cognition. This disruption of sleep is also known to occur with alcohol and benzodiazepines.

Cardinal rule 3. Only positive things should happen in bed, meaning either intimacy or sleep. No negative issues should occur in bed. If the patient can’t sleep after 10 or 20 minutes of relaxation, then he or she should go back to the “ritual chair” and begin the process again. Too many chronic insomniacs teach themselves how not to sleep, thus perpetuating their insomnia.

Cardinal rule 4. No napping! Any sleep that occurs between wake-up time and bedroom time is considered napping. Napping only further disrupts the sleep–wake cycle and continues the vicious cycle of insomnia. Some medical problems necessitate resting during the day. If this is the case, a 30-minute rest after lunch may be necessary.

Consequences of Sleep Apnea

Obstructive sleep apnea (OSA), although not as common as insomnia, is estimated to occur in 15 million Americans and lately has received an increasing amount of attention. This sleep disorder may cause “environmental insomnia” for the bed partner and others in the home because of loud snoring. Like OSA, its precursor, snoring itself has been reported to cause several health problems. Some studies suggest that snoring is associated with hypertension, ischemic heart disease, and stroke, although other studies do not support this finding (13). Lee and colleagues found that “heavy snoring significantly increases the risk of carotid atherosclerosis, and the increase is independent of… nocturnal hypoxemia and obstructive sleep apnea severity” (14). They suggested that the transmission of vibrations during snoring is one of the pathophysiologic mechanisms associated with the development of carotid disease. Another study found that heavy snoring was associated with case fatality and short-term mortality after a first acute myocardial infraction (15). Snoring was not associated with long-term mortality rates.

OSA has been associated with a worse long-term prognosis, although there are conflicting reports regarding this association. OSA with hypoxia leads to ischemia and arrhythmia, and it directly depresses cardiac contractility (13). OSA may also be involved in the generation of oxygen free radicals. Sleep-disordered breathing is associated with a rise in circulating levels of other inflammatory cytokines as well as vascular adhesion molecules, all of which damage the cardiovascular system. Endothelial dysfunction has been associated with OSA (16). A consensus document on sleep apnea and cardiovascular disease stated that OSA is associated with hypertension, coronary artery disease, stroke, and atrial fibrillation (17). Central sleep apnea, in which the brain temporarily stops sending signals to the muscles that control breathing, occurs mainly in patients with heart failure, but also in patients using high doses of narcotics. A meta-analysis of sleep apnea in patients with stroke and transient ischemic attack (TIA) found a common association, regardless of the type of stroke, and the authors concluded that sleep studies should be considered in all patients after stroke or TIA (18).

The American Diabetes Association recommends that all diabetic patients be screened for OSA. Sleep-disordered breathing is associated with increased sympathetic nerve activity and catecholamine (adrenaline) release, which may promote hyperinsulinemia. This association between OSA and insulin resistance was seen in both obese and non-obese subjects. Each additional episode of apnea or hypopnea per sleep hour increased the fasting insulin level and insulin resistance (measured by the homeostasis model assessment of insulin resistance; HOMA-IR) by about 0.5%(19). Several studies also noted a dose-response relationship between the severity of nocturnal hypoxemia caused by sleep-disordered breathing and the degree of insulin resistance (20, 21).

In my experience, any patient who snores and is sleepy during the day deserves a sleep study to evaluate the possibility of OSA. Recent studies have evaluated screening nocturnal oximetry with oxygen desaturation index as a powerful screening tool (22). A ResMed ApneaLink apparatus is also available for home screening use. Typical physical findings in OSA patients include a crowded posterior airway space caused by an elongated palate, enlarged tonsils, a large tongue, and/or an overbite. Retrognathia is a common finding in non-obese patients with significant OSA.

Treatment of Sleep Apnea

The only treatment proved effective for this disorder is continuous positive airway pressure (CPAP). Surgical correction of the crowded posterior airway space usually gives less impressive results. Compliance with CPAP is a common problem but can be overcome with instruction from an experienced sleep specialist. One of the most common adverse effects with CPAP use is nasal obstruction caused by vasomotor rhinitis and/ordeviation of the nasal septum. Vasomotorrhinitis can be treated with nasal antihistamines and the proper use of CPAP humidification. Surgery may be needed to repair adeviated septum. In addition, the use of a nasal pillow apparatus instead of the CPAP mask may also help with CPAP compliance.

When used consistently, CPAP improves glycemic control. Diabetic patients who used CPAP nightly for at least 4 hours had significant decreases in fasting and postprandial blood sugar levels averaging 50–80 mg/dl(23). Use of CPAP for more than 4 hours also resulted in better control of blood sugar level sand fewer days with elevated levels, which in turn resulted in lower glycosylated hemoglobin and metabolic improvement in diabetic patients. CPAP is thought to reverse the impairment in glucose homeostasis caused by OSA. Another study noted that CPAP treatment rapidly improved insulin sensitivity in patients with OSA (24).

Conclusions

Sleep disorders, particularly insomnia and OSA, are associated with many metabolic disorders, cardiovascular disease, and diabetes. Therefore, sleep disorders must be addressed when taking a patient’s history and a review of systems. Simply ask a few questions such as the following:

• Do you have difficulty sleeping, getting to sleep, or staying asleep?
• Do you snore? Are you sleepy during the day?
• Do your legs bother you while trying to rest during the evening?

By asking these simple questions and further evaluating those with a positive response, we may eliminate the need for additional anti-hypertensive and/or anti diabetic medications. We may also decrease the frequency of conditions that are possibly caused by untreated OSA, such as nocturnal sinus pauses requiring the placement of pacemakers and recurrent atrial fibrillation. In addition, if an underlying sleep disorder is discovered and treated, expensive evaluations for memory loss may not be necessary. Remember, memory is worsened by poor sleep, and better sleep leads to a better day!

Dr. Ledet is the Director of Preventive Care & Sleep Medicine in Mobile and in Daphne, Alabama. He is board certified in Family Medicine and Clinical Lipidology. He serves as the Medical Director of the Southeastern Regional Sleep/Wake Disorders Center at Springhill Medical Center in Mobile, Alabama; and he serves as an Assistant Clinical Professor in the Department of Family Medicine at the University of South Alabama College of Medicine. He is on the speaker’s bureau of Abbott, Atherotech, Cephalon, GlaxoSmithKline, Sanofi-Aventis, Sepracor, and Takeda Pharmaceuticals.

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