Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index

Abstract

Background: Sleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown.

Methods and findings: Study participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors. A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI.

Conclusion: Participants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity.

Figure 1. Sample Construction and Data Collected

All employees (aged 30–60 y) of four state agencies in south central Wisconsin were mailed surveys starting in 1989 regarding general health and sleep habits. From this population, a stratified random sample of respondents was recruited for an extensive overnight protocol providing polysomnography and sleep questionnaire data and morning, fasted serum for hormone and metabolite measurement. The metabolic hormones measured were ghrelin (856 participants), leptin (1,017 participants), adiponectin (1,015 participants), and insulin (1,014 participants) (see Table 1). Based on scheduling availability, 721 participants completed an added protocol to measure daytime sleepiness that included a 6-d sleep diary, of which 714 reported on naps (see Table 1). See text for further description of the study population and definitions of the sleep measures used.

Figure 2. The Relationship between BMI and Average Nightly Sleep

Mean BMI and standard errors for 45-min intervals of average nightly sleep after adjustment for age and sex. Average nightly sleep values predicting lowest mean BMI are represented by the central group. Average nightly sleep values outside the lowest and highest intervals are included in those categories. Number of visits is indicated below the standard error bars. Standard errors are adjusted for within-subject correlation.

Figure 3. The Association between Sleep Duration and Serum Leptin and Ghrelin Levels

(A) Mean leptin levels and standard errors for half-hour increments of average nightly sleep after adjustment for age, sex, BMI, and time of storage (see Table 2). Average nightly sleep values outside the lowest and highest intervals are included in those categories. Sample sizes are given below the standard error bars. The y-axis uses a square-root scale. Data derived from 718 diaries because three participants had missing leptin data. (B) Mean ghrelin levels and standard errors for half-hour increments of total sleep time after adjustment for age, sex, BMI, and time of storage (see Table 2). Total sleep time values outside the lowest and highest intervals are included in those categories. The y-axis uses a square-root scale. Note that ranges for total sleep time amounts are typically shorter than those for average nightly sleep amounts (A; see Figure 1), and do not correlate strongly (see text).