Exposure to recurrent sleep restriction in the setting of high caloric intake and physical inactivity results in increased insulin resistance and reduced glucose tolerance

Abstract

Context: Epidemiological data indicate that reduced sleep duration is associated with increased incidence of type-2 diabetes.

Objective: The aim of the study was to test the hypothesis that, when part of a Western-like lifestyle, recurrent bedtime restriction may result in decreased glucose tolerance and reduced insulin secretion and action.

Design and setting: We conducted a randomized crossover study at a university clinical research center and sleep research laboratory.

Participants: Eleven healthy volunteers (five females and six males) with a mean (+/-sd) age of 39 +/- 5 yr and body mass index of 26.5 +/- 1.5 kg/m(2) participated in the study.

Intervention: The study included two 14-d periods of controlled exposure to sedentary living with ad libitum food intake and 5.5- or 8.5-h bedtimes.

Main outcome measures: Oral and iv glucose challenges were used to obtain measures of glucose tolerance, glucose effectiveness, insulin secretion, and insulin sensitivity at the end of each intervention. Secondary measures included circulating concentrations of the glucose counter-regulatory hormones, cortisol, GH, epinephrine, and norepinephrine.

Results: Bedtime restriction reduced daily sleep by 122 +/- 25 min. Both study periods were associated with comparable weight gain; however, recurrent sleep restriction resulted in reduced oral glucose tolerance (2-h glucose value, 144 +/- 25 vs. 132 +/- 36 mg/dl; P < 0.01) and insulin sensitivity [3.3 +/- 1.1 vs. 4.0 +/- 1.6 (mU/liter)(-1) x min(-1); P < 0.03], and increased glucose effectiveness (0.023 +/- 0.005 vs. 0.020 +/- 0.005 min(-1); P < 0.04). Although 24-h cortisol and GH concentrations did not change, there was a modest increase in 24-h epinephrine and nighttime norepinephrine levels during the 5.5-h bedtime condition.

Conclusions: Experimental bedtime restriction, designed to approximate the short sleep times experienced by many individuals in Westernized societies, may facilitate the development of insulin resistance and reduced glucose tolerance.

Figure 1

Mean (+se) concentrations of glucose (A) and insulin (B) in response to a 75-g oral glucose challenge at the end of the 8.5-h (open circles) and 5.5-h (solid circles) bedtime condition. Asterisk indicates that both the 2-h value and the 3-h AUC were significantly different between the two sleep conditions. AUC, Area under the curve.

Figure 2

Mean (+se) 24-h profiles of circulating counter-regulatory hormones measured at the end of the 8.5-h (open circles) and 5.5-h (solid circles) bedtime condition. Significant differences in the 24-h, daytime (0900–2300 h), and nighttime (2300–0900 h) concentrations between the two bedtime conditions are identified with an asterisk. A, Serum cortisol concentrations (n = 11); B, best-fit regression curves illustrating the 24-h cortisol rhythm (n = 11); C, GH secretory rates derived by deconvolution analysis (n = 11); D, serum GH concentrations (n = 11); E, serum GH concentrations in male study participants (n = 6); F, serum GH levels in female study participants (n = 5); G, plasma epinephrine (E) concentrations (n = 7); H, plasma norepinephrine (NE) concentrations (n = 7). The timing of the iv glucose challenge and lunch and dinner meals is marked by vertical gray lines and gray shaded bars, respectively.

Figure 3

Mean (+se) profiles of circulating counter-regulatory hormones measured before (baseline, BL) and every 30 min after an iv glucose challenge at the end of the 8.5-h (open circles) and 5.5-h (solid circles) bedtime conditions. Significant differences between the two bedtime conditions are identified with an asterisk. A, Plasma glucose concentrations during the IVGTT (n = 11); B, serum insulin concentrations during the IVGTT (n = 11); C, hourly serum cortisol concentrations (n = 11); D, hourly plasma epinephrine (E) concentrations (n = 7); E, hourly serum GH concentrations (n = 11); F, hourly plasma norepinephrine (NE) concentrations (n = 7). *, P < 0.05 in post hoc comparisons between the two bedtime conditions based on repeated measures ANOVA.