In the present study after six years of follow-up, short sleep was associated with a significant, three-fold increased likelihood of developing IFG even after considering several putative diabetes risk factors. This estimate was slightly attenuated but no longer statistically significant when the role of insulin resistance on this observed association was examined, suggesting that insulin resistance explains some but not all of the association. To our knowledge no other studies have reported specifically on the sleep-IFG association but the present study’s estimates are in accord with previous studies that have examined the sleep-impaired glucose tolerance (IGT) association. However, other studies have been hampered by their cross-sectional design. For example, the Quebec Family Study examined the association between average sleep and the combined endpoint of (IGT) and type 2 diabetes in 223 Canadian families (n=740) (12
). The odds of developing a glucose impairment was twice as high among short sleepers and 58% greater among long sleepers compared to mid-range sleepers (p<0.05 for both). The Sleep Heart Health Study (13
) reported the OR of type 2 diabetes was 2.5 times greater among the shortest sleepers (<5h night), and about 70% greater among persons sleeping <6h or ≥ 9h a night vs. 7-8h. Similarly, people who slept 6h carried a 60% excess likelihood of having IGT (P<0.001 for all). Like these studies and others that have examined the sleep-type 2 diabetes association(10
) long duration was also found to be a significant predictor of disordered glucose metabolism. The present study found that long sleep duration >8h increased the likelihood of IFG by 60%, however, our findings were not statistically significant, perhaps because of the limited number of case subjects (n=5) in this sleep category. Although short and long sleep duration have both been found to elevate the risk of disordered glucose metabolism, the underlying mechanisms are thought to differ.
There are several plausible biologic pathways through which sleep loss can lead to disordered glucose metabolism. One mechanism is through alterations in the neurohormonal regulation of feeding behaviors. Experimentally, acute sleep curtailment resulted in a 28% increase in mean levels of the appetite stimulating hormone ghrelin, and an 18% decrease in the anorexigenic hormone leptin. Moreover, sleep restriction was significantly associated with self-reported increased hunger and appetite especially for calorie dense foods, despite normalizing caloric intake via a continuous glucose infusion(20
Another possible pathway by which reduced sleep may lead to type 2 diabetes is through the activation of the sympathetic nervous system (SNS). Experimental studies have shown that sleep restriction decreases glucose tolerance, and increases cortisol levels and heart rate variability (21
). These neuroendocrine changes interfere with mechanisms that regulate plasma glucose, resulting in a higher steady state plasma glucose concentration (23
The activation of inflammatory pathways may also play a role in the observed association between short sleep duration and impaired glucose metabolism. Experimental studies have shown that reduced sleep is associated with increased TNF-α, IL-6 and CRP (24
). Moreover, it is well established that inflammation predicts subsequent type 2 diabetes (26
Finally, the possibility that short sleep duration may represent a risk marker rather than a causal risk factor for diseases cannot be ruled out at the present time. In fact, short sleepers are likely to be characterized by a distinctive pattern of socio-demographic, lifestyle, and co-morbid medical conditions that may confound the observed associations (28
). Data on sleep quality were not available therefore we were unable to assess the presence of sleep disorders such as obstructive sleep apnea. It is possible that differences in the reasons for short sleep duration (eg. self- imposed sleep restriction, sleep loss due to family or job demands, or underlying illness) might affect the observed sleep- IFG association, but we were unable to directly examine this issue.
One limitation of the present study is that sleep duration was self-reported, not objectively measured which may result in a systematic over-reporting of sleep duration (8
). Over-reporting would most likely be random, non-differential, which would dilute the sleep-IFG association. Another limitation is that we did not control for some comorbid conditions that may inhibit longer sleep duration such as, incontinence, esophageal reflux, or arthritis. However, adjustment was made for several diseases that have been shown to be associated with diabetes including hypertension and depression. In addition, reliance on a single FPG measure at the baseline and follow-up examinations to categorize normoglycemic and IFG subjects could have resulted in an under-diagnosis of IFG as well as misclassification: the directionality of the potential bias is unknown. Fasting glucose measures are highly correlated over time (our own data show the correlation coefficient is r=0.60 for repeat FPG measures over a six year period). Nevertheless the American Diabetes Association supports the use of one fasting measure in epidemiologic studies. (30
There are several notable strengths of this study: Participants were randomly selected from the general population of Erie and Niagara counties and are racially representative of these counties. In addition, the matched design improves internal validity by decreasing variability between cases and controls, resulting in an analysis that is more sensitive to the association of interest. Furthermore, the selection of three control participants per case rather than just one enhanced statistical power. Also, these data include both men and women and a wide age range (35-79 years). Nevertheless, because of the matched design and lack of racial diversity these findings may not be generalized to other populations.
In summary, persons who self-reported short sleep duration were three times more likely to develop IFG compared to those whose average sleep was 6-8 h a night. This association can be explained in part by insulin resistance.