Invited Commentary: To Sleep, Perchance to Discover

Kingman P. Strohl

From the Center for Sleep Disorders Research, Case Western Reserve University, 10701 East Blvd., Cleveland, OH 44122 (e-mail: kpstrohl{at}aol.com).


    INTRODUCTION
 TOP
 INTRODUCTION
 REFERENCES
 
Sleep and sleep disorders are important in public health (1Go). Insomnia (the perception of inadequate or unrefreshing sleep) occurs in 20–35 percent of the US population (1Go) and has adverse economic and neurophysiological outcomes. Moderate degrees of sleepiness are self-reported in 30 percent of the population (1Go). There is now a recognized need to promote sufficient diagnosis of sleep disorders in order to prevent accidents, motor vehicle crashes, and occupational errors due to somnolence (2Go). Disorders such as obstructive sleep apnea, hypopnea syndrome, and restless-legs syndrome are present in 2–4 percent of the population and occur at a higher prevalence (10–40 percent) among persons with neuromuscular diseases, renal failure, hypertension, and heart disease (1Go). Planning for optimizing adolescent sleep by delaying school starting times is under study with regard to its potential educational benefit for high school and college students (2Go). The article by Al-Delaimy et al. (3Go) in this issue of the Journal reinforces these points by demonstrating an association between sleep behavior and the subsequent development of type II diabetes mellitus.

Sleep quantity and quality are associated epidemiologically with early mortality, hypertension, and all-cause cardiovascular disease risk (1Go, 4Go, 5Go). Self-reported snoring appears to be important in this association, probably as a marker for respiratory disorders of sleep, including obstructive sleep apnea. How one asks a question about snoring is an obvious concern, since snoring is usually recognized by the "snoree" rather than the "snorer"; however, studies have suggested that reports of snoring by patients and their bed partners are similar (6Go), and in my opinion subjective estimates are probably sufficient to avoid egregious misclassification in population studies. Al-Delaimy et al. (3Go) present results from analysis of a 10-year follow-up (1986–1996) of the Nurses' Health Study cohort and focus on the 1986 responses to questions on "occasional snoring" and "regular snoring" with regard to subsequent diagnosis of diabetes. From the findings of their analysis, it appears that snoring could be a novel independent risk factor for the development of type II diabetes in women.

The report discusses the potential pathway between snoring and sleep apnea, particularly the notion that sleep apnea produces a "neuroexcitatory state" through sympathetic activation by repetitive apneas and hypoxemia. There is reasonable support for this position (7Go). However, there is an emerging body of literature showing that sleep itself, independent of snoring, is important in glucose and insulin regulation. Sleep restriction in healthy subjects results in higher fasting glucose levels and decreased insulin sensitivity—markers often found in persons at risk for diabetes (8Go, 9Go). Common to sleep apnea, sleep restriction, and fragmentation could be the activation of the hypothalamic-pituitary stress axis, resulting in higher circulating cortisol levels. Alternatively, short sleep and interrupted sleep flatten growth hormone surges known to be associated with uninterrupted slow-wave sleep, but how this might relate to diabetes is unclear. Overall, the finding that sleep loss adversely affects insulin sensitivity is important, since sleep debt is present in several populations (10Go, 11Go) and may be more common in women (12Go).

Snoring could be a marker for other characteristics. Persons who snore are more likely to have allergies and nasal obstruction during the day, and possibly they are less physically fit than nonsnorers. Because sleep interruption results in daytime fatigue, snorers may drink more caffeinated drinks (coffee or cola), which have a more noticeable alerting effect in sleepy persons than in nonsleepy persons (13Go). Snoring and sleep apnea are linked to alcohol consumption (14Go), which in turn is linked to insulin resistance (15Go). Finally, snorers may use more over-the-counter medications, such as nasal vasoconstrictive sprays, which have some adrenergic effect that may impair glucose uptake (16Go).

The co-occurrence of sleep apnea with features of "Syndrome X"—hypertension, obesity, diabetes, and hyperlipidemia—has prompted a call to change the moniker to "Syndrome Z" (17Go). This cluster of diseases may occur through a common set of neuroendocrine factors (18Go). The observation in the Nurses' Health Study data of an association between snoring and hypertension (19Go) may rely on such mechanisms. Previous reports from the Nurses' Health Study have found that moderate alcohol consumption and heart-healthy dietary habits protect against the development of cardiovascular disease (20Go, 21Go) and that regular exercise and/or weight stability protect against the risk of being diagnosed with diabetes (22Go, 23Go). Alcohol use and weight gain are thought to be risk factors for snoring and sleep apnea, and exercise and weight maintenance are thought to be mitigating factors for apnea expression (14Go, 24Go). Thus, the Nurses' Health Study data set is in a position to address the linkage between elements in "Syndrome Z" and to address the potentially beneficial effect of alcohol on cardiovascular disease risk versus the detriment of alcohol in promoting snoring.

Both the physiologic plausibility of sleep problems' being related to insulin resistance and the evidence of there being an epidemiologic association between snoring and cardiovascular disease risk factors are strong. The strength of these findings offers investigators a rationale for beginning to examine previously unexplored relations in relational databases that have incorporated questions on sleep into the participants' health profiles. Supporting this proposal is the finding from a twin study that the trait of snoring appears to be only loosely genetically linked to the trait of obesity (25Go). Speaking directly to the Nurses' Health Study data set (19Go, 21GoGo–23Go, 26Go, 27Go), it would be possible to address the effects of obesity, alcohol use, and lack of exercise on hypertension, cardiovascular disease risk, and diabetes before and after adjustment for snoring. If adjustment for exercise results in an increase in risk, prevalence, or incidence of diabetes after adjustment for snoring, then exercise might be considered relatively more important than snoring. If the opposite occurs, snoring might be assigned a more fundamental role.

Such proposed analyses are not merely hypothesis-generating exercises. Sleep health is an important dimension of personal health. The evidence now accumulated suggests that problems regarding sleep are related to numerous common US diseases and therefore have direct implications for national disease prevention and health promotion strategies.


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Received for publication October 10, 2001. Accepted for publication October 30, 2001.


Related articles in Am. J. Epidemiol.:

Snoring as a Risk Factor for Type II Diabetes Mellitus: A Prospective Study
Wael K. Al-Delaimy, JoAnn E. Manson, Walter C. Willett, Meir J. Stampfer, and Frank B. Hu
Am. J. Epidemiol. 2002 155: 387-393. [Abstract] [FREE Full Text]