Can sleep medicine play a role in controlling the nation’s diabetes epidemic?
Obstructive sleep apnea (OSA) is an increasingly recognized condition in patients with diabetes. Although no prospective studies have been performed to determine whether diabetes is a cause of OSA, cross-sectional analyses have confirmed that OSA is more prevalent in diabetic patients than in the general population. One such analysis was performed on nearly 1,400 participants of the Wisconsin Sleep Cohort.1 Full polysomnography was used to characterize OSA in the study participants. Then these results were compared with information on whether the participants had diabetes. The results showed that there was a greater prevalence of diabetes in subjects with increasing severity of OSA. Among subjects with an apnea-hypopnea index (AHI) of 15 or more, 15% had a diagnosis of diabetes, compared with only 3% of subjects with an AHI of less than 5. The investigators concluded that diabetes is more prevalent in patients with OSA, and this relationship appeared to be independent of other risk factors.
A similar observation was noted in an earlier exploratory survey in which investigators asked patients about symptoms of OSA, nocturia, excessive daytime sleepiness, lower urinary tract symptoms, and self-rated health.2 The patient sample (n=87) included a majority of women (61%) and obese persons (60%). The mean age was 64 years, and 40% were self-reported type 2 diabetic patients. The diabetic patients had significantly more OSA symptoms, more nocturia, and poorer self-rated health. Results of a stepwise logistic regression showed that persons with diabetes and those who reported excessive daytime sleepiness experienced a three- to four-fold greater risk for OSA than others in the survey sample.
Diabetes Overview
Diabetes mellitus is one of the oldest diseases known. A chronic condition, it is marked by hyperglycemia; disturbances in carbohydrate, fat, and protein metabolism; and insulin deficiency or inactivity.
As diabetes progresses, the pancreas either produces little or no insulin, or the cells of the body do not respond to the insulin that is produced. As a result, glucose builds up in the blood, and the body naturally tries to get rid of this excess glucose. Consequently, glucose overflows into the urine, and passes out of the body. Thus, the body loses its main source of fuel even though the blood contains large amounts of glucose. An extra blow is that high levels of blood glucose actually harm body cells—so not only does diabetes starve cells of the glucose they need, but the hyperglycemia of diabetes may directly damage the cells as well.
There are two major types of diabetes: type 1 (formerly called insulin-dependent diabetes or IDDM), and type 2 (formerly called non–insulin-dependent diabetes or NIDDM). Type 1 diabetes occurs when the pancreas produces little or no insulin. To live, the person with type 1 diabetes needs daily injections of insulin. Type 1 diabetes accounts for 5% to 10% of the cases of diagnosed diabetes in the United States. It usually begins during the first two decades of life, but can develop up to around age 40.
The more common form of diabetes is type 2 diabetes, which makes up more than 90% of diabetes cases.3 Type 2 diabetes usually begins in obese individuals over age 30 and usually responds well to oral hypoglycemic agents. In type 2 diabetes, the pancreas usually produces insulin, but for some reason, the body cannot use the insulin efficiently. The end result is the same as for type 1 diabetes—an inability to use glucose efficiently and an unhealthy buildup of glucose in the blood.
Obesity and Type 2 Diabetes
Type 2 diabetes has several well-established risk factors. The first is age. The chances of developing type 2 diabetes increases as people get older. There is also a very strong link between family history and the development of type 2 diabetes. People in several ethnic groups also have a high risk of type 2 diabetes—these include Native-Americans, Hispanic-Americans, African-Americans, and Asian-Americans.4-5
However, the most important risk factor for type 2 diabetes is being overweight or obese. The prevalence of obesity in the United States is staggering. In its most recent analysis of data from the Third National Health and Nutrition Examination Survey, the Centers for Disease Control and Prevention found that 85% of Americans are overweight or obese, and 55% of Americans are obese.6
Researchers have discovered that it is not just the amount of body fat that is important, but where the fat is distributed on the body. Increased body fat at or above the waist (central adiposity) is more of a risk factor for type 2 diabetes than body fat below the waist.7 Inactivity also adds to type 2 diabetes risk.8 Exercise is important in preventing the development of diabetes because it improves the body’s use of glucose. Long-term stress may also increase the chances of developing type 2 diabetes.9
People without diabetes who consume excessive calories and gain weight develop insulin resistance, especially in muscles. Beta cells compensate for this resistance by secreting more insulin. Throughout most of their lives, obese people are in a state of hyperinsulinemia. At first, glucose tolerance remains normal or is only slightly impaired. But as more years pass or as more weight is gained, insulin secretion—although still high—may no longer be able to counteract insulin resistance, and type 2 diabetes may develop.
One theory to explain the association between diabetes and OSA is that the events in OSA trigger different, perhaps unique, adaptations in metabolic processes involving insulin action and glucose regulation.10 A likely underlying cause of the increased risk of OSA in diabetic patients is obesity. A strong association has been noted between obesity, impaired glucose tolerance, insulin resistance, and sleep-disordered breathing.11-13
Although OSA is the most common type of sleep-disordered breathing observed in patients with diabetes, central-type apneas and periodic breathing also have been reported in patients with diabetes and autonomic diabetic neuropathy.13
The association between obesity and OSA is well recognized. Weight gain in patients with OSA usually results in an increase in the severity of apnea. It has long been hypothesized, and later documented by magnetic resonance imaging, that the region surrounding the collapsible segment of the pharynx in patients with OSA has a greater fat load than does the same region in equally obese patients who do not have OSA. This finding—in conjunction with the finding of an increase in airway resistance and a decrease in airway stability documented when applying lard-filled bags to the neck to simulate cervical fat accumulation—suggests that the effect of obesity on OSA might be related to local parapharyngeal fat deposits.14 Histopathologic studies of uvulas excised during uvulopalatopharyngoplasty for OSA have demonstrated higher amounts of both fat and muscle mass compared with those seen during normal postmortem studies.14-16
Treating the Diabetic OSA Patient
While diabetes, like OSA, is a chronic condition, it can be managed and this should be the first step to treating OSA in the diabetic patient. Evidence suggests that patients with hypoglycemia during sleep who are treated appropriately exhibit improved sleep efficiency and increased slow-wave sleep.17 Diabetes treatment strategies should emphasize sustained blood glucose control, cardiovascular risk reduction, and correction of associated dyslipidemia. A variety of drugs are available for the treatment of type 2 diabetes, including sulfonylureas (eg, glimepiride, glipizide, glyburide); biguanides (eg, metformin), thiazolidinediones (eg, rosiglitazone, pioglitazone); meglitinides (eg, repaglinide); alpha-glucosidase inhibitors (eg, miglitol, acarbose); glucagon-like peptide-1 analogs (eg, exenatide); and amylin analogs (eg, pramlintide). Sometimes combinations of drugs are prescribed.
Because the link between obesity and both OSA and diabetes is strong, diet, exercise, and weight reduction are also important cornerstones of disease management in patients with both disorders. Anecdotal cases suggest that for some patients, the better sleep they get with effective OSA treatment also may help them lose weight,18 possibly by decreasing fatigue that discourages exercise and by reducing their need to consume sugary drinks and snacks to stay alert during the day.
Treatments for OSA include behavioral modification, drug therapy, and use of mechanical devices. Behavioral modifications include avoidance of alcohol and sedative medications, alteration of sleep position, avoidance of sleep deprivation, and weight loss. Drug therapy for OSA is of limited clinical value, with the exception of thyroxine replacement in patients with hypothyroidism.19
Nasal CPAP is the initial treatment of choice for OSA in adults and can reduce mortality associated with OSA.20 However, although effective, CPAP is uncomfortable or intolerable for some patients, and variable patient compliance remains a significant problem. Studies have found that up to 25% of patients discontinue CPAP therapy.21,22
Surgical options for the management of severe OSA include uvulopalatopharyngoplasty (UPPP); laser-assisted UPPP (LAUP); uvulopalatopharyngoglossoplasty; linguoplasty; laser midline glossectomy; inferior sagittal mandibular osteotomy and genioglossal advancement with hyoid myotomy and suspension; and maxillomandibular osteotomy.23-25 UPPP and laser-assisted UPPP are the most common surgical procedures performed for severe OSA. LAUP has been reported to reduce morbidity, such as pain and bleeding, as compared to traditional UPPP.25 LAUP is also less expensive and may require less time off from work. The other, more complicated surgical procedures are limited to only a few instit-utions, and may be associated with significant postoperative morbidity.
Conclusion
Obesity is the most common cause of OSA in diabetic patients with OSA. The cornerstones of treatment are appropriate management of diabetes and achievement of weight loss. If OSA does not improve with these steps, then treatment options for OSA itself should be considered. These include behavioral modifi-cation, drug therapy, use of mechanical devices, CPAP, and surgery.
The consequences of OSA can be significant for those with the condition, as well as for their bed partners and family members. Although many patients try to self-manage their symptoms, most will eventually seek treatment if the symptoms are unrelenting and/or progressive. Optimal management depends on accurate diagnosis, which includes identification of obesity and other possible triggers, and institution of the appropriate therapeutic modalities.
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