Effect of sleep restriction on insulin sensitivity and energy metabolism in postmenopausal women: A randomized crossover trial

Abstract

Objective: The aim of this study was to investigate the effect of sleep restriction (SR) on insulin sensitivity and energy metabolism in postmenopausal women.

Methods: In a randomized crossover trial, 14 women underwent four nights of habitual sleep (HS, 100% normal sleep) and SR (60% of HS) while following a eucaloric diet. Outcomes included the following: (1) insulin sensitivity by hyperinsulinemic-euglycemic clamp, defined as the glucose infusion rate (GIR); (2) resting metabolism and substrate oxidation by indirect calorimetry; and (3) glucose, insulin, and C-peptide concentrations following a standard meal test.

Results: Nine postmenopausal women (mean [SD], age 59 [4] years, BMI 28.0 [2.6] kg/m² ) were analyzed. Accelerometer-determined total time in bed was 8.4 ± 0.6 hours during HS versus 5.0 ± 0.4 hours during SR (38% reduction, p < 0.0001). SR reduced low-dose insulin GIR by 20% (HS: 2.55 ± 0.22 vs. SR: 2.03 ± 0.20 mg/kg/min; p = 0.01) and high-dose insulin GIR by 12% (HS: 10.48 ± 0.72 vs. SR: 9.19 ± 0.72 mg/kg/min; p < 0.001). SR reduced fat oxidation during high-dose insulin infusion (p < 0.01), and it did not alter resting energy metabolism.

Conclusions: Four nights of SR reduced insulin sensitivity and fat oxidation in postmenopausal women. These findings underscore the role of insufficient sleep in metabolic dysfunction following menopause. Larger trials investigating how sleep disturbances cause metabolic dysfunction during menopause are needed across all stages of menopause.

Trial registration: ClinicalTrials.gov NCT04286451.

Figure 1.. Study Protocol

Prior to each intervention arm, women wore an accelerometer for 7 days to measure habitual sleep habits for determining prescribed sleep bedtime, waketime, and ultimately total in-bed duration. Each intervention arm consisted of 4 nights of habitual sleep (100% of normal sleep duration) or 4 nights of sleep restriction (40% reduction in habitual sleep, including 20% delayed sleep onset and 20% early waking) and then to crossover to the other arm after a minimum 3-week washout period. On day 4, women consumed a standard meal test (Ensure^® Original Nutritional Shakes, 440-kcal) while serum blood was collected (indicated by ▲) over a 2-hour period from approximately 6:00 to 8:00 PM. On day 5, women awoke at their prescribed waketime for inpatient assessment of insulin sensitivity measured by a 2-step hyperinsulinemic-euglycemic clamp, as well as REE and RER measured by indirect calorimetry (IC) during both low-dose and high-dose insulin infusion. Serum blood was collected during each steady-state period (indicated by ▲). Urine was also collected throughout the duration of the clamp for calculation of urinary nitrogen excretion. * Denotes the 40% reduction in habitual sleep included 20% delayed sleep onset and 20% early waking.

Figure 2.. Participant flow diagram

Individuals were initially assessed via an online questionnaire followed by an in person visit. If an individual failed to meet a criterion, that person was excluded, and no further criteria were measured. Furthermore, individuals who did not have confirmed ≥6.5 hours of habitual nightly sleep by accelerometry were excluded from the trial prior to randomization.

Figure 3.. Insulin Sensitivity

Sleep restriction dramatically lowered both low-dose (left) and high-dose (right) insulin GIR by 20% and 12%, respectively. These alterations were the result of reduced non-oxidative component of GIR by 39% during low-dose and 16% during high-dose clamp segments. Oxidative GIR was unaffected. All data are presented as 9 paired sleep conditions. Data are presented as least squares mean ± SEM. (**p≤0.01 and ***p≤0.001).

Figure 4.. Glycemic Control

In response to a standard meal test, (A) sleep restriction did not affect individual glucose concentrations (main) or overall glucose AUC (inset); (B) sleep restriction did not affect individual insulin concentrations (main), but overall insulin AUC trended towards being reduced by 15% (p=0.07) (inset); and (C) sleep restriction did not affect individual C-peptide concentrations (main) or overall C-peptide AUC (inset). All data are presented as 9 paired sleep conditions. Data are presented as least squares mean ± SEM. (^†0.05<p≤0.10).