Quantification of sleep behavior and of its impact on the cross-talk between the brain and peripheral metabolism

Abstract

Rates of obesity have been steadily increasing, along with disorders commonly associated with obesity, such as cardiovascular disease and type II diabetes. Simultaneously, average sleep times have progressively decreased. Recently, evidence from both laboratory and epidemiologic studies has suggested that insufficient sleep may stimulate overeating and thus play a role in the current epidemic of obesity and diabetes. In the human sleep laboratory it is now possible to carefully control sleep behavior and study the link between sleep duration and alterations in circulating hormones involved in feeding behavior, glucose metabolism, hunger, and appetite. This article focuses on the methodologies used in experimental protocols that have examined modifications produced by sleep restriction (or extension) compared with normal sleep. The findings provide evidence that sleep restriction does indeed impair glucose metabolism and alters the cross-talk between the periphery and the brain, favoring excessive food intake. A better understanding of the adverse effects of sleep restriction on the CNS control of hunger and appetite may have important implications for public health.

Fig. 1.

Mean prevalence of short sleep duration over race/ethnic group, adjusted for age: Alameda County Health and Ways of Living Study, 1965–1999. Sample size and response rate for each follow-up were as follows: 1974 (n = 4,864; 85%), 1983 (50% of random sample of eligible subjects, n = 1,799; 87%), 1994 (n = 2,730; 93%), and 1999 (n = 2,123; 95%). Short sleep at baseline was calculated across categories for each covariate, including frequency, prevalence, and odds ratio. A generalized estimating equation approach for statistical testing with regard to short sleep, race/ethnic group, income, and education was used owing to the repeated nature of the data (10). African Americans (P < 0.0001) and Hispanics (P < 0.001) showed significantly greater increase over time in the prevalence of short sleep duration compared with whites. (Reprinted from ref. , Copyright 2007, with permission from Elsevier.)

Fig. 2.

(A) Experimental protocol included three baseline nights of 8 h in bed (white bars), followed by six night of sleep restriction (4 h in bed; black bars), ending with a seven night period of sleep extension (12 h in bed; light gray bars). The last 2 d of the sleep-debt and sleep-extension periods included identical meals for breakfast, lunch, and dinner (small arrows), an ivGTT to assess glucose metabolism (large arrow), and 24-h blood sampling to examine circulating hormonal profiles (dashed lines). (B) In a randomized cross-over design, two nights of either bedtime extension (10 h in bed; dark gray bars) or sleep restriction (4 h in bed; black bars) were followed by 12 h of blood sampling, coupled with a constant glucose infusion and hourly questionnaires regarding hunger/appetite, mood, and sleepiness. (C) In a randomized cross-over design, two nights of normal sleep (8 h in bed; white bars) or three nights of slow-wave sleep suppression (hatched bars) were followed by an ivGTT (arrow) to assess glucose metabolism.

Fig. 3.

Adapted from refs. , , , and . Percentage change relative to the well-rested condition for measures of glucose metabolism in young healthy lean adults subjected to either sleep restriction (Upper; five nights of 4-h bedtimes, n = 11) or slow-wave sleep (SWS) suppression (Lower; three nights, n = 9). In each study, comparisons between well-rested condition and sleep restriction (Upper) or SWS suppression (Lower) were made by paired t test.

Fig. 4.

Adapted from refs. and . Upper: Mean (±SEM) daytime profiles of plasma leptin and ghrelin observed in 12 healthy lean subjects after 2 d of 4-h bedtimes or 2 d with 10-h bedtimes. Caloric intake was exclusively administered via a constant glucose infusion. Comparisons between the two sleep conditions were performed using the Wilcoxon test for matched pairs; leptin decrease 18% (P = 0.04) and ghrelin increase 28% (P < 0.04). Correlation of the change in hunger ratings and the ghrelin/leptin ratio were calculated using the Spearman rank test. Values were calculated using data from 4 h in bed minus the value obtained after 10 h in bed. The calculated value was negative when the variable measured after 10 h in bed was higher than that measured after 4 h in bed. Lower: Mean (±SEM) 24-h plasma leptin profiles obtained from nine healthy lean men studied at bed rest who ate three identical carbohydrate-rich meals after 6 d of 4 h, 8 h, and 12 h in bed. Comparisons of variables obtained during 8-h, 4-h, and 12-h bedtime conditions were performed using ANOVA for repeated measures. Time spent asleep in each condition was as follows; 3 h 48 min in 4-h bedtime condition, 6 h 52 min in 8-h bed condition, and 8 h 52 min in the 12-h condition. Note that the characteristics of the 24-h leptin profile (amplitude, nocturnal maximum, and overall mean) increased from the 4-h to the 12-h bedtime condition. Dark bars denote sleep periods.