Selective slow wave sleep but not rapid eye movement sleep suppression impairs morning glucose tolerance in healthy men

Summary

Shortened nocturnal sleep impairs morning glucose tolerance. The underlying mechanism of this effect is supposed to involve a reduced fraction of slow wave sleep (SWS). However, it remains unanswered if impaired glucose tolerance occurs due to specific SWS reduction or a general disturbance of sleep. Sixteen healthy men participated in three experimental conditions in a crossover design: SWS suppression, rapid eye movement (REM)-sleep disturbance, and regular sleep. Selective sleep stage disturbance was performed by means of an acoustic tone (532 Hz) with gradually rising sound intensity. Blood concentrations of glucoregulatory parameters were measured upon an oral glucose tolerance test the next morning. Our data show that morning plasma glucose and serum insulin responses were significantly increased after selective SWS suppression. Moreover, SWS suppression reduced postprandial insulin sensitivity up to 20%, as determined by Matsuda Index. Contrastingly, disturbed REM-sleep did not affect glucose homeostasis. We conclude that specifically SWS reduction is critically involved in the impairment of glucose tolerance associated with disturbed sleep. Therefore, glucose metabolism in subjects predisposed to reduced SWS (e.g. depression, aging, obstructive sleep apnea, pharmacological treatment) should be thoroughly monitored.

Introduction

National surveys in the USA revealed that the average time spent asleep has been reduced by approximately 2 h over the past century (Gangwisch et al., 2007). This is alarming since epidemiological studies indicate a link between habitual short sleep duration and an increased risk of obesity (Cappuccio et al., 2008), arterial hypertension (Gottlieb et al., 2006), cardiovascular disease (Nagai et al., 2010), and the metabolic syndrome in general (Jennings et al., 2007). Specifically, habitual short sleep duration is associated with an increased risk of type 2 diabetes mellitus (DM) (Gottlieb et al., 2005, Gangwisch et al., 2007). Considering the comorbid overweight in type 2 DM, it suggests itself that the association between poor sleep and type 2 DM may be due to the body weight-promoting effects of sleep loss because a chronic lack of sleep assumingly fosters the development of obesity (Schmid et al., 2009, Benedict et al., 2011, Benedict et al., 2012). This view, however, does not explain why acute and subchronic episodes of sleep loss examined under laboratory conditions impair glucose tolerance even in normal weight volunteers (Spiegel et al., 2005, Buxton et al., 2010, Donga et al., 2010, van Leeuwen et al., 2010).

Beyond the known detrimental effects of sleep time restriction, it has been shown that disturbed sleep quality represents a risk factor for type 2 DM (Stamatakis and Punjabi, 2010, Kita et al., 2012;), which leads to the assumption that a disarranged sleep architecture per se impacts glucose metabolism. In this context, a previous study suggested that subchronic deprivation (i.e., 3 nights) of slow wave sleep (SWS), without sleep time restriction, impairs morning glucose tolerance (Tasali et al., 2008). However, because this study did not involve a comparison condition examining the effects of non-SWS disturbance, the question if general sleep disruption or sleep stage-specific disturbances influence glucose homeostasis remains unsettled.

In order to clarify this question, we aimed to differentiate between the impact of SWS-suppression and disturbed sleep architecture during non-SWS episodes on glucose metabolism under conditions of physiological sleep duration. To this aim, the effects of one night of selective SWS suppression on morning glucose tolerance were compared with those after a night of REM-sleep disturbance and normal sleep as a control condition.