Sleep restriction for 1 week reduces insulin sensitivity in healthy men

Abstract

Objective: Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness.

Research design and methods: This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20-35 years and BMI 20-30 kg/m(2)). Subjects spent 10 h/night in bed for >or=8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured.

Results: IVGTT-derived insulin sensitivity was reduced by (means +/- SD) 20 +/- 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 +/- 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 +/- 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep.

Conclusions: Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.

Trial registration: ClinicalTrials.gov NCT00895570.

FIG. 1.

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

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.

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.

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: S_I from IVGTT. H: relative changes in S_I 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).