Sleep-disordered breathing, glucose intolerance, and insulin resistance
Introduction
Sleep-disordered breathing (SDB) is a disorder that is characterized by recurrent collapse of the upper airway during sleep. Population-based epidemiologic data indicate that 4% of adult men and 2% of adult women may have this chronic condition (Young et al., 1993). Patients with SDB often present with complaints of loud disruptive snoring, witnessed apneas, fatigue, and daytime sleepiness. SDB can disrupt nocturnal sleep continuity and lead to a number of adverse cardiovascular complications. Recent data from the Wisconsin Sleep Cohort Study and the Sleep Heart Health Study indicate that SDB is an independent risk factor for hypertension (Young et al., 1997, Nieto et al., 2000, Peppard et al., 2000) and prevalent cardiovascular disease (Shahar et al., 2001). Clinic based studies also suggest that SDB may lead to increased cardiovascular morbidity and mortality (Mooe et al., 2001).
Given the emerging data on the potential contribution of SDB to the occurrence of cardiovascular disease, a number of studies have examined intermediate mechanisms in the putative causal pathway. In particular, the effects of SDB on glucose tolerance and insulin sensitivity have received increasing attention in recent years. The focus on the metabolic implications of SDB is based on several studies that suggest an independent association between SDB, glucose intolerance, and insulin resistance. In light of the trends in the prevalence of obesity, glucose intolerance and insulin resistance are becoming increasing prevalent in the general population. Data from the Third National Health and Nutrition Examination Survey indicate that 5.1% of the adults in the United States have physician-diagnosed diabetes and an additional 2.7% meet the criterion for diabetes but remain undiagnosed (Harris et al., 1998). It is also estimated that 6.9% of the adults have impaired fasting glucose levels (≥110 mg/dl) and 15.6% have glucose intolerance (Harris et al., 1998). Since SDB and metabolic dysfunction share common etiologic risk factors (e.g. central obesity), rigorous control for such confounders is critical in establishing whether a causal link exists between the two disorders.
Although definitive evidence to support a causal association is still lacking, there are several lines of indirect evidence that have implicated SDB as an independent risk factor for glucose intolerance and insulin resistance. First, there is evidence that SDB is associated with an increase in sympathetic activity (Somers et al., 1995, Fletcher, 1997, Narkiewicz and Somers, 1997). Sympathetic hyperactivity can impair glucose homeostasis by increasing glycogen breakdown and gluconeogenesis. Second, data from animal models suggest that exposure to hypoxia can induce a state of insulin resistance (Cheng et al., 1997, Raff et al., 1999, Raff et al., 2001). Third, curtailment of sleep duration and secondary sleep debt, a common occurrence in SDB, can impair glucose tolerance in normal subjects (Spiegel et al., 1999). Although a number of previous studies have examined the relationship between SDB and metabolic dysfunction, the possibility of a causal link remains controversial given that the effects of obesity and other confounders have not been adequately addressed. The purpose of this study was to systematically review and critically appraise the evidence for the link between SDB, glucose intolerance, and insulin resistance.
Section snippets
Methods
A computerized bibliographic search of the MEDLINE database was performed to identify articles in the English language published between 1966 through June 2002. The following key words were used in the search: ‘insulin resistance’, or ‘glucose intolerance’, or ‘diabetes’ or ‘metabolic diseases’, and ‘sleep apnea syndromes’. Additional searches included use of the following exploded MeSH terms: ‘sleep apnea syndromes’ and ‘metabolic diseases’. Abstracts of each of the resulting articles were
Results
A total of 969 studies were identified through the computerized bibliographic search of the MEDLINE database. Abstracts of all the studies were reviewed independently by two of the authors and a final set of 24 articles that met the inclusion criteria were selected for the final review. These articles were classified into three categories: studies on the association between markers of SDB (e.g. snoring, witnessed apneas) and metabolic dysfunction (Table 1), studies of polysomnographically
Discussion
The results of this systematic review suggest SDB is independently associated with glucose intolerance and insulin resistance. The presence of habitual snoring, a marker for SDB, is associated with an increased prevalence of metabolic abnormalities and confers a higher risk for the development of type 2 diabetes mellitus independent of obesity and other covariates. Although studies on the relationship between snoring and metabolic dysfunction have been methodologically rigorous in accounting
References (52)
- et al.
Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP)
Respir. Med.
(1999) - et al.
Metabolic correlates with obstructive sleep apnea in obese subjects
J. Pediatr.
(2002) - et al.
Serum leptin and vascular risk factors in obstructive sleep apnea
Chest
(2000) - et al.
Adiposity and cardiovascular risk factors in men with obstructive sleep apnea
Chest
(1993) - et al.
CPAP treatment does not affect glucose-insulin metabolism in sleep apneic patients
Sleep Med.
(2001) - et al.
Impact of sleep debt on metabolic and endocrine function
Lancet
(1999) - et al.
Snoring as a risk factor for type II diabetes mellitus: a prospective study
Am. J. Epidemiol.
(2002) - et al.
Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness
J. Clin. Endocrinol. Metab.
(1994) - et al.
Effect of hypoxia on blood glucose, hormones, and insulin receptor functions in newborn calves
Pediatr. Res.
(1997) - et al.
Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy
Circulation
(1999)
Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment
Sleep
Fasting glucose homeostasis in rats after chronic exposure to hypoxia
Am. J. Physiol.
Plasma insulin and lipid levels in untreated obstructive sleep apnoea and snoring; their comparison with matched controls and response to treatment
J. Sleep Res.
Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients
Am. J. Respir. Crit. Care Med.
The role of habitual snoring and obesity in the development of diabetes, a 10-year follow-up study in a male population
J. Intern. Med.
Sleep-disordered breathing and glucose metabolism in hypertensive men, a population-based study
J. Intern. Med.
Prevalence and correlates of snoring and observed apneas in 5201 older adults
Sleep
Sympathetic activity and blood pressure in the sleep apnea syndrome
Respiration
Snoring and sleep apnoea in men, association with central obesity and hypertension
Int. J. Obes. Relat. Metab. Disord.
Impact of obstructive sleep apnea and sleepiness on metabolic and cardiovascular risk factors in the Swedish obese subjects (SOS) Study
Int. J. Obes. Relat. Metab. Disord.
Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults. The Third National Health and Nutrition Examination Survey, 1988–1994
Diabetes Care
Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications
Eur. Respir. J.
Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance
Science
Tumor necrosis factor alpha inhibits signaling from the insulin receptor
Proc. Natl. Acad. Sci. USA
Obstructive sleep apnea is independently associated with insulin resistance
Am. J. Respir. Crit. Care Med.
Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old population
Eur. J. Epidemiol.
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