Sleep restriction increases free fatty acids in healthy men

Abstract

Aims/hypothesis: Sleep loss is associated with insulin resistance and an increased risk for type 2 diabetes, yet underlying mechanisms are not understood. Elevation of circulating non-esterified (i.e. free) fatty acid (NEFA) concentrations can lead to insulin resistance and plays a central role in the development of metabolic diseases. Circulating NEFA in healthy individuals shows a marked diurnal variation with maximum levels occurring at night, yet the impact of sleep loss on NEFA levels across the 24 h cycle remains unknown. We hypothesised that sleep restriction would alter hormones that are known to stimulate lipolysis and lead to an increase in NEFA levels.

Methods: We studied 19 healthy young men under controlled laboratory conditions with four consecutive nights of 8.5 h in bed (normal sleep) and 4.5 h in bed (sleep restriction) in randomised order. The 24 h blood profiles of NEFA, growth hormone (GH), noradrenaline (norepinephrine), cortisol, glucose and insulin were simultaneously assessed. Insulin sensitivity was estimated by a frequently sampled intravenous glucose tolerance test.

Results: Sleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels.

Conclusions/interpretation: Sleep restriction in healthy men results in increased nocturnal and early-morning NEFA levels, which may partly contribute to insulin resistance and the elevated diabetes risk associated with sleep loss.

Fig. 1

Study protocol. Black bars, consecutive nights with bedtimes from 23:00 hours to 07:30 hours in the normal sleep condition; red bars, consecutive nights with bedtimes from 01:00 hours to 05:30 hours in the sleep restriction condition; dotted lines, 24 h blood-sampling period; thin arrows, the identical meals served at 09:00, 14:00 and 19:00 hours; thick arrows, IVGTT

Fig. 2

Twenty-four hour profiles of NEFA (a), GH (b), noradrenaline (c) and cortisol (d) under conditions of normal sleep (black lines) and sleep restriction (red lines) in N=19 participants. Error bars are SEM. Horizontal black bars, time in bed under normal sleep (23:00 to 07:30 hours); horizontal red bars, time in bed under sleep restriction (01:00 to 05:30 hours); arrows, identical meals served at 09:00, 14:00 and 19:00 hours. *p<0.05 for sleep restriction vs normal sleep at specific time points

Fig. 3

Twenty-four hour profiles of glucose (a, b) and insulin (c, d) under conditions of normal sleep (black lines) and sleep restriction (red lines) in N=19 participants. Error bars are SEM. Horizontal black bars, time in bed under normal sleep (23:00–07:30 hours); horizontal red bars, time in bed under sleep restriction (01:00–05:30 hours); arrows, identical meals served at 09:00, 14:00 and 19:00 hours; vertical lines, AUC over the first postprandial 2.5 h after the breakfast meal

Fig. 4

AUC values for glucose (a) and insulin (b) after breakfast, lunch and dinner under conditions of normal sleep (black bars) and sleep restriction (red bars) in N=19 participants. Error bars are SEM. Identical meals were served at 09:00, 14:00 and 19:00 hours. The AUCs were calculated using the trapezoidal method over the postprandial 2.5 h for each meal. *p<0.05 sleep restriction vs normal sleep

Fig. 5

(a) Insulin sensitivity from IVGTTs under conditions of normal sleep (black bars) and sleep restriction (red bars) in N=19 participants. **p<0.01 sleep restriction vs normal sleep. Error bars are SEM. To convert values to SI units, multiply by 0.167. (b) Correlation between the change in nocturnal NEFA levels and the change in insulin sensitivity in n=16 participants. Changes during sleep restriction are expressed as percentage of the values obtained during normal sleep. r= −0.52; p=0.05