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Metabolism

Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men

  1. Orfeu M. Buxton1,2,
  2. Milena Pavlova2,3,
  3. Emily W. Reid1,
  4. Wei Wang1,2,
  5. Donald C. Simonson1,2 and
  6. Gail K. Adler1,2
  1. 1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts;
  2. 2Harvard Medical School, Boston, Massachusetts;
  3. 3Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
  1. Corresponding author: Orfeu M. Buxton, orfeu_buxton{at}hms.harvard.edu.
Diabetes 2010 Sep; 59(9): 2126-2133. https://doi.org/10.2337/db09-0699
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  • FIG. 1.
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    FIG. 1.

    Protocol schema. (See research design and methods for a detailed description.)

  • FIG. 2.
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    FIG. 2.

    Subjective sleepiness and lapses of attention under sleep restriction conditions. Effects of sleep restriction on subjective sleepiness (top panel) and lapses of attention (bottom panel). Subjective sleepiness and objective lapses of attention in sleep-replete subjects were assessed after 10 h of TIB per night and after restricting sleep to 5 h/night over 1 week (days 1–6 averages) in subjects randomized to placebo (red circles) or modafinil administration (green triangles). Subjective sleepiness is defined as mean deviation from baseline Karolinska Sleepiness Scale (KSS). Lapses of attention are defined as reaction times >500 ms and are quantified as the absolute deviation from baseline (lapses/test per day). For self-reported sleepiness, we noted significant main effects of sleep restriction (P < 0.0001), treatment (P < 0.0001), and their interaction (P < 0.0001). With modafinil administration, self-reported sleepiness was significantly reduced compared with placebo after the first and second nights of sleep restriction only (P = 0.0276). For lapses of attention, there was a significant main effect of number of nights of sleep restriction (P = 0.0012) and a borderline effect for treatment (P = 0.0647), and their interaction was nonsignificant (P = 0.1488). With modafinil administration, lapses of attention were significantly reduced compared with placebo during the daytime testing after the first and second nights of sleep restriction only (P = 0.0141); after the second and third nights, the borderline P values were 0.0779 and 0.0770, respectively.

  • FIG. 3.
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    FIG. 3.

    Salivary (free) cortisol levels with sleep restriction. Salivary cortisol levels were assessed hourly from 1500 to 2100 h under sleep-replete conditions (10 h/night TIB [black circles]) and under sleep-restricted conditions (5 h/night TIB for 1 week) in subjects receiving placebo (red circles) or modafinil (green triangles). Salivary cortisol levels (means ± SD) from 1500 to 2100 h were significantly affected by sleep duration only: 0.13 ± 0.03 ng/ml for the sleep-replete condition and 0.17 ± 0.04 ng/ml for the sleep-restricted condition (P < 0.0001 and Table 1). Identical (mixed composition) dinners were served just after the 1800-h saliva sample and finished before 1840 h.

  • FIG. 4.
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    FIG. 4.

    Effects of sleep restriction on glucose metabolism. A and B: Mean glucose levels (± SE) from IVGTT during the baseline sleep-replete condition (10 h/night TIB [black line]) and following sleep restriction for 1 week (5 h/night TIB) in subjects receiving placebo (A) (red line) modafinil (B) (green line). Left arrow, glucose infusion at time = 0 min; right arrow, insulin infusion at time = 20 min. C and D: Mean insulin levels (± SE) from IVGTT. E–H: IVGTT parameters were calculated using Minmod Millennium software. Glucose and insulin data from insulin-modified IVGTT procedures under sleep-replete (filled symbols) and sleep-restricted conditions (open symbols) are shown. E: Acute insulin response (AIRg) (first phase). F: Disposition index. G: SI from IVGTT. H: relative changes in SI from IVGTT expressed as percent change from baseline sleep-replete condition in subjects randomized to placebo (red circles) or modafinil administration (green triangles). I: Insulin sensitivity (M) from euglycemic-hyperinsulinemic clamp procedure. J: Relative changes in insulin sensitivity (M) depicted as in F. There were no significant effects of drug administration on any metabolic parameters (Table 1).

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  • TABLE 1
    Sleep duration (TIB per study day)Baseline vs. sleep restriction condition (P)Drug (P)Interaction (P)
    ModafinilPlacebo
    5 h10 h5 h10 h
    Sleepiness: KSS (1–9 scale)4.65 ± 0.123.23 ± 0.135.31 ± 0.113.61 ± 0.16<0.0001<0.0001<0.0001
    Performance: PVT lapses (lapses · test−1 · day−1)4.09 ± 0.452.48 ± 0.375.10 ± 0.730.92 ± 0.18<0.00010.0080.002
    Sleep duration: total sleep time (min)268.2 ± 3.5502.2 ± 8.9274.0 ± 1.4467.4 ± 10.8<0.00010.040.001
    Slow-wave sleep (min)78.6 ± 3.475.2 ± 5.975.4 ± 3.265.2 ± 7.40.120.500.57
    FSIVGTT
        SI [(mU/l)−1 · min−1]4.61 ± 0.555.70 ± 0.884.81 ± 0.786.74 ± 0.940.0010.620.24
        Acute insulin response (mU · l−1 · min)549.2 ± 127.2514.0 ± 106.3532.3 ± 94.1566.7 ± 112.80.300.770.81
        Disposition index2,034.2 ± 231.62,500.6 ± 391.92,079.5 ± 254.12,993.7 ± 431.60.020.460.52
        Glucose tolerance (%/min)−1.984 ± 0.137−2.295 ± 0.160−2.120 ± 0.162−2.465 ± 0.2610.020.430.62
        Glucose effectiveness (min−1)0.017 ± 0.0020.020 ± 0.0020.021 ± 0.0020.023 ± 0.0030.210.150.76
    Clamp: M (mg · kg−1 · min−1)6.15 ± 0.667.11 ± 0.866.95 ± 0.817.39 ± 0.790.050.550.69
    Salivary cortisol (ng/ml)0.179 ± 0.0170.112 ± 0.0130.180 ± 0.0150.125 ± 0.010<0.00010.700.48
    Catecholamines
        Norepinephrine (μg/day)48.0 ± 4.529.7 ± 4.332.5 ± 4.427.5 ± 4.7<0.00010.140.02
        Epinephrine (μg/day)13.5 ± 1.27.0 ± 0.89.0 ± 2.17.4 ± 1.10.0010.290.03
    Resting metabolic rate (kcal)1,931.4 ± 77.41,928.6 ± 79.11,851.0 ± 86.41,853.0 ± 116.60.990.560.96
    • Data are means ± SE unless otherwise indicated.

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Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men
Orfeu M. Buxton, Milena Pavlova, Emily W. Reid, Wei Wang, Donald C. Simonson, Gail K. Adler
Diabetes Sep 2010, 59 (9) 2126-2133; DOI: 10.2337/db09-0699

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Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men
Orfeu M. Buxton, Milena Pavlova, Emily W. Reid, Wei Wang, Donald C. Simonson, Gail K. Adler
Diabetes Sep 2010, 59 (9) 2126-2133; DOI: 10.2337/db09-0699
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