Chronic inadequate sleep is associated with increased risk of cardiometabolic diseases. The mechanisms involved are poorly understood but involve changes in insulin sensitivity, including within adipose tissue. The aim of this study was to assess the effects of sleep restriction on nonesterified fatty acid (NEFA) suppression profiles in response to an intravenous glucose tolerance test (IVGTT) and to assess whether 2 nights of recovery sleep (a “weekend”) is sufficient to restore metabolic health. We hypothesized that sleep restriction impairs both glucose and lipid metabolism, specifically adipocyte insulin sensitivity, and the dynamic lipemic response of adipocyte NEFA release during an IVGTT. Fifteen healthy men completed an inpatient study of 3 baseline nights (10 h of time in bed/night), followed by 5 nights of 5 h of time in bed/night and 2 recovery nights (10 h of time in bed/night). IVGTTs were performed on the final day of each condition. Reductions in insulin sensitivity without a compensatory change in acute insulin response to glucose were consistent with prior studies (insulin sensitivity P = 0.002; acute insulin response to glucose P = 0.23). The disposition index was suppressed by sleep restriction and did not recover after recovery sleep ( P < 0.0001 and P = 0.01, respectively). Fasting NEFAs were not different from baseline in either the restriction or recovery conditions. NEFA rebound was significantly suppressed by sleep restriction ( P = 0.01) but returned to baseline values after recovery sleep. Our study indicates that sleep restriction impacts NEFA metabolism and demonstrates that 2 nights of recovery sleep may not be adequate to restore glycemic health.

Supplementary key words triglycerides • nutrition • lipolysis and fatty acid metabolism • diet and dietary lipids • fatty acid • insulin resistance • inflammation • hormones • glucose According to the Centers for Disease Control and Prevention, one in three US adults sleeps fewer than 7 h per night, increasing their risk of obesity and for risk of developing CVD, type 2 diabetes, and earlier mortality, among other comorbidities (1-4). The mechanisms by which chronic insufficient sleep increases cardiometabolic disease risk are poorly understood, but results from carefully controlled laboratory studies demonstrate that sleep restriction simultaneously increases orexigenic hormonal signaling and impairs glucose metabolic functioning (5, 6). Furthermore, there is mounting evidence that adipocyte insulin sensitivity and function are impaired by sleep restriction resulting in aberrantly elevated overnight and early morning NEFAs (7-10). Adipocytes are a key integrator of systemic metabolism, absorbing and storing excess energy postprandially and releasing stored fatty acids as needed to meet the energy requirements of the body (11). Adipocytes respond to the postprandial increase in insulin by suppressing intracellular TG lipolysis and by increasing extracellular lipolysis by transporting LPL from intracellular vesicles to the surface Abstract Chronic sleep restriction, or inadequate sleep, is associated with increased risk of cardiometabolic disease. Laboratory studies demonstrate that sleep restriction causes impaired whole-body insulin sensitivity and glucose disposal. Evidence suggests that inadequate sleep also impairs adipose tissue insulin sensitivity and the NEFA rebound during intravenous glucose tolerance tests, yet no studies have examined the effects of sleep restriction on high-fat meal lipemia. We assessed the effect of 5 h time in bed (TIB) per night for four consecutive nights on postprandial lipemia following a standardized high-fat dinner (HFD). Furthermore, we assessed whether one night of recovery sleep (10 h TIB) was sufficient to restore postprandial metabolism to baseline. We found that postprandial triglyceride (TG) area under the curve was suppressed by sleep restriction (P = 0.01), but returned to baseline values following one night of recovery. Sleep restriction decreased NEFAs throughout the HFD (P = 0.02) and NEFAs remained suppressed in the recovery condition (P = 0.04). Sleep restriction also decreased participant-reported fullness or satiety (P = 0.03), and decreased postprandial interleukin-6 (P < 0.01). Our findings indicate that four nights of 5 h TIB per night impair postprandial lipemia and that one night of recovery sleep may be adequate for recovery of TG metabolism, but not for markers of adipocyte function.

The effects of sleep restriction on subjective alertness, motivation, and effort vary among individuals and may explain interindividual differences in attention during sleep restriction. We investigated whether individuals with a greater decrease in subjective alertness or motivation, or a greater increase in subjective effort (versus other participants), demonstrated poorer attention when sleep restricted. Participants and Methods: Fifteen healthy men (M±SD, 22.3±2.8 years) completed a study with three nights of 10-hour time in bed (baseline), five nights of 5-hour time in bed (sleep restriction), and two nights of 10-hour time in bed (recovery). Participants completed a 10-minute psychomotor vigilance task (PVT) of sustained attention and rated alertness, motivation, and effort every two hours during wake (range: 3-9 administrations on a given day). Analyses examined performance across the study (first two days excluded) moderated by per-participant change in subjective alertness, motivation, or effort from baseline to sleep restriction. For significant interactions, we investigated the effect of study day 2 (day*day) on the outcome at low (mean−1 SD) and high (mean+1 SD) levels of the moderator (N = 15, all analyses). Results: False starts increased across sleep restriction in participants who reported lower (mean−1 SD) but not preserved (mean+1 SD) motivation during sleep restriction. Lapses increased across sleep restriction regardless of change in subjective motivation, with a more pronounced increase in participants who reported lower versus preserved motivation. Lapses increased across sleep restriction in participants who reported higher (mean+1 SD) but not preserved (mean−1 SD) effort during sleep restriction. Change in subjective alertness did not moderate the effects of sleep restriction on attention. Conclusion: Vigilance declines during sleep restriction regardless of change in subjective alertness or motivation, but individuals with reduced motivation exhibit poorer inhibition. Individuals with preserved subjective alertness still perform poorly during sleep restriction, while those reporting additional effort demonstrate impaired vigilance.

Objective: Sleep restriction alters daytime cardiac activity, including elevating heart rate (HR) and blood pressure (BP). There is minimal research on the cumulative effects of sleep loss and the response after subsequent recovery sleep on HR and BP. This study examined patterns of HR and BP across baseline, sleep restriction, and recovery conditions using multiple daytime cardiac measurements. Methods: Participants (15 healthy men, mean [standard deviation] = 22.3 [2.8] years) completed an 11-day inpatient protocol with three nights of 10 hours/night baseline sleep opportunity, five sleep restriction nights (5-hour/night sleep opportunity), and two recovery nights (10-hour/night sleep opportunity). Resting HR and BP were measured every 2 hours during wake. Multilevel models with random effects for individuals examined daytime HR and BP across study conditions and days into the study. Results: Mean daytime HR was 1.2 (0.5) beats/min lower during sleep restriction compared with baseline ( p < .001). During recovery, HR was 5.5 (1.0) beats/min higher ( p < .001), and systolic BP (SBP) was 2.9 (1.1) mm Hg higher ( p = .009). When accounting for days into the study (irrespective of condition) and measurement timing across the day, HR increased by 7.6 beats/min and SBP increased by 3.4 mm Hg across the study period ( p < .001). Conclusions: Our findings suggest that daytime HR and SBP increase after successive nights of sleep restriction, even after accounting for measurement time of day. HR and SBP did not recover to baseline levels after two recovery nights of sleep, suggesting that longer recovery sleep may be necessary to recover from multiple, consecutive nights of moderate sleep restriction.

We investigated whether interindividual attentional vulnerability moderates performance on domain-specific cognitive tasks during sleep restriction (SR) and subsequent recovery sleep. Fifteen healthy men (M ± SD, 22.3 ± 2.8 years) were exposed to three nights of baseline, five nights of 5-h time in bed SR, and two nights of recovery sleep. Participants completed tasks assessing working memory, visuospatial processing, and processing speed approximately every two hours during wake. Analyses examined performance across SR and recovery (linear predictor day or quadratic predictor day2) moderated by attentional vulnerability per participant (difference between mean psychomotor vigilance task lapses after the fifth SR night versus the last baseline night). For significant interactions between day/day2 and vulnerability, we investigated the effect of day/day2 at 1 SD below (less vulnerable level) and above (more vulnerable level) the mean of attentional vulnerability (N = 15 in all analyses). Working memory accuracy and speed on the Fractal 2-Back and visuospatial processing speed and efficiency on the Line Orientation Task improved across the entire study at the less vulnerable level (mean − 1SD) but not the more vulnerable level (mean + 1SD). Therefore, vulnerability to attentional lapses after SR is a marker of susceptibility to working memory and visuospatial processing impairment during SR and subsequent recovery.