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Does lack of sleep cause diabetes?

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Obstructive sleep apnea and diabetes

The most robust evidence that not only short sleep duration but also poor sleep quality affects diabetes risk comes from studies of metabolic function in patients with obstructive sleep apnea, an increasingly common condition.

Obstructive sleep apnea is characterized by recurrent episodes of partial or complete upper airway obstruction with intermittent hypoxia and microarousals, resulting in low amounts of slow-wave sleep and overall decreased sleep quality.54

Obstructive sleep apnea is common in patients with type 2 diabetes, and several clinical and epidemiologic studies suggest that, untreated, it may worsen diabetes risk or control.21,45–46,55–59

The Sleep AHEAD (Action for Health in Diabetes) study60 revealed, in cross-sectional data, that more than 84% of obese patients with type 2 diabetes had obstructive sleep apnea (with an apnea-hypopnea index ≥ 5).

Aronsohn et al,5 in a study conducted in our laboratory in 60 patients with type 2 diabetes, found that 46 (77%) of them had obstructive sleep apnea. Furthermore, the worse the obstructive sleep apnea, the worse the glucose control. After controlling for age, sex, race, body mass index, number of diabetes medications, level of exercise, years of diabetes, and total sleep time, compared with patients without obstructive sleep apnea, the adjusted mean hemoglobin A1c was increased in a linear trend by (in absolute percentage points):

  • 1.49% in patients with mild obstructive sleep apnea (P = .0028)
  • 1.93% in patients with moderate obstructive sleep apnea (P = .0033)
  • 3.69% in patients with severe obstructive sleep apnea (P < .0001).

Other epidemiologic studies. A growing number of epidemiologic studies, in various geographic regions, have suggested an independent link between obstructive sleep apnea and risk of type 2 diabetes.61 Most of the studies have been cross-sectional, and while most had positive findings, a criticism is that the methodology varied among the studies, both in how obstructive sleep apnea was assessed (snoring vs polysomnography) and in the metabolic assessment (oral glucose tolerance test, homeostatic model assessment, hemoglobin A1c, medical history, physician examination, or patient report).

So far, 14 population studies (Table 1) have assessed obstructive sleep apnea with polysomnography,5,45,55,62–72 but only two of them were prospective.64,65 Of the cross-sectional studies, all but the earliest study, which also was the smallest,62 found an association between the increased severity of obstructive sleep apnea and alterations in glucose metabolism consistent with an increased risk of diabetes. The one retrospective study63 and the first published prospective study64 did not find an independent relationship between the severity of obstructive sleep apnea at baseline and the incidence of diabetes. Of note, the duration of follow-up in the prospective study was only 4 years, which may not be sufficient.64

A more recent prospective study of 544 nondiabetic patients65 showed that the risk of developing type 2 diabetes over an average of 2.7 years of follow-up was a function of the severity of obstructive sleep apnea expressed in quartiles: for each increased quartile of severity there was a 43% increase in the incidence of diabetes. Additionally, in patients with moderate to severe sleep apnea, regular use of continuous positive airway pressure (CPAP) was associated with an attenuated risk.65

Two prospective studies (not included in Table 1) used snoring as a marker of obstructive sleep apnea; at 10 years of follow-up, snoring was associated with a higher risk of developing diabetes in both men and women.73,74

Does CPAP improve glucose metabolism? Other studies have specifically examined the effects of CPAP treatment on glucose metabolism, in both diabetic and nondiabetic populations. Accumulating evidence suggests that metabolic abnormalities can be partially corrected by CPAP treatment, which supports the concept of a causal link between obstructive sleep apnea and altered glucose control. This topic is beyond the scope of this review; please see previously published literature61,75 for further information. Whether treating obstructive sleep apnea may delay the development or reduce the severity of type 2 diabetes is another important unanswered question.

Is obstructive sleep apnea a cause or consequence of diabetes? It may be a novel risk factor for type 2 diabetes, and its association with altered glucose metabolism is well supported by a large set of cross-sectional studies, but there are still insufficient longitudinal studies to indicate a direction of causality.

If obstructive sleep apnea is the cause, what is the mechanism? There are likely many. High levels of sympathetic nervous system activity, intermittent hypoxia, sleep fragmentation, and sleep loss in obstructive sleep apnea may all lead to dysregulation of the hypothalamic-pituitary axis, endothelial dysfunction, and alterations in cytokine and adipokine release and are all potential mechanisms of abnormal glucose metabolism in this population.

WHAT TO TELL PATIENTS

Taken together, the current evidence suggests that strategies to improve the duration and the quality of sleep should be considered as a potential intervention to prevent or delay the development of type 2 diabetes mellitus in at-risk populations. While further studies are needed to better elucidate the mechanisms of the relationship between sleep loss and diabetes risk and to determine if extending sleep and treating obstructive sleep apnea decreases the risk of diabetes, we urge clinicians to recommend at least 7 hours of uninterrupted sleep per night as a goal in maintaining a healthy lifestyle. Additionally, clinicians should systematically evaluate the risk of obstructive sleep apnea in their patients who have type 2 diabetes mellitus and the metabolic syndrome, and conversely, should assess for diabetes in patients with known obstructive sleep apnea.

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