Daytime eating prevents internal circadian misalignment and glucose intolerance in night work

Abstract

Night work increases diabetes risk. Misalignment between the central circadian “clock” and daily behaviors, typical in night workers, impairs glucose tolerance, likely due to internal misalignment between central and peripheral circadian rhythms. Whether appropriate circadian alignment of eating can prevent internal circadian misalignment and glucose intolerance is unknown. In a 14-day circadian paradigm, we assessed glycemic control during simulated night work with either nighttime or daytime eating. Assessment of central (body temperature) and peripheral (glucose and insulin) endogenous circadian rhythms happened during constant routine protocols before and after simulated night work. Nighttime eating led to misalignment between central and peripheral (glucose) endogenous circadian rhythms and impaired glucose tolerance, whereas restricting meals to daytime prevented it. These findings offer a behavioral approach to preventing glucose intolerance in shift workers.

Fig. 1.. Conceptual scheme for meal timing effects in shift work settings, study aims, and experimental design.

(A) Top: Night work, whereby meals typically occur at night, is hypothesized to misalign central and peripheral circadian oscillators. Bottom: Night work, whereby meals occur during the day, is aimed to align central and peripheral circadian oscillators (internal circadian alignment). (B) In this study, we tested whether endogenous circadian rhythms of metabolic markers (glucose and insulin) can be entrained to an FD 28-hour sleep/wake and 28-hour fasting/eating cycles, resulting in a misalignment between the central circadian pacemaker and metabolic organs, and in impaired glucose tolerance. We tested whether restricting food intake to the daytime (on a 24-hour cycle) during a 28-hour sleep/wake cycle maintains internal circadian alignment and appropriate glucose tolerance. (C) The 14-day laboratory study design presented as relative clock time (for a participant whose habitual wake-up schedule was 7 a.m.). Participants were randomized to the Nighttime meal control (NMC) group or the Daytime meal intervention (DMI) group (see Methods for details on the study design). Meals consumed during the FD protocol (including the identical test meals) are included in the scheme (see text for detailed timings). Isocaloric snacks were consumed hourly during the CR protocols.

Fig. 2.. Effects of meal timing intervention on central and peripheral circadian rhythms after simulated night work.

(A and B) The meal timing intervention did not significantly modify the impact of simulated night work on the endogenous circadian CBT rhythms. Accordingly, simulated night work did not significantly affect the endogenous circadian CBT rhythms, as compared to baseline, in the NMC group (A) or in the DMI group (B). (C and D) The meal timing intervention significantly modified the impact of simulated night work on the endogenous circadian glucose rhythms. Accordingly, simulated night work significantly affected the endogenous circadian glucose rhythms, as compared to baseline, in the NMC group (C), but not in the DMI group (D). (E and F) The change from baseline to simulated night work in the phase of the endogenous circadian CBT rhythms did not significantly differ between groups [inverted triangles in (E) and (F)]. In contrast, the change from baseline to simulated night work in the phase of the circadian glucose rhythms significantly differed between groups [circles in (E) and (F)]. In the NMC group, the phase shift of the endogenous circadian glucose rhythms closely matched the 12-hour shift of the sleep/wake cycle induced by the 28-hour FD protocol (which was not observed in the DMI group). Data in (A) to (D) were grouped into 15°-circadian windows (~1-hour resolution) with SEM error bars and the top x axes were scaled to the approximate group-averaged time of the CBT minimum for reference (i.e., relative clock time). Data in (A) to (D) correspond to the average (mean ± SEM) across participants per simulated day/night work condition and per meal timing group (n = 10 in the NMC group and n = 9 in the DMI group). Individual (symbols) and group-averaged (arrows) data are presented in (E) to (F).

Fig. 3.. Effects of meal timing intervention on endogenous circadian insulin rhythms after simulated night work.

(A and B) The meal timing intervention did not significantly modify the impact of simulated night work on the endogenous circadian insulin rhythms. [NMC group (A), DMI group (B)]. Bottom x axis: Data grouped into 15°-circadian windows (~1-hour resolution) with SEM error bars. We scaled top x axes to the time of the CBT minimum. Data in (A) and (B) correspond to the average (mean ± SEM) across participants per simulated day/night work condition and per meal timing group (n = 10 in the NMC group and n = 9 in the DMI group).

Fig. 4.. Effects of meal timing intervention on glucose tolerance after the breakfast test meal.

The meal timing intervention significantly modified the impact of simulated night work on the 3-hour postprandial glucose and early-phase insulin profiles after the breakfast test meal. Simulated night work in the NMC group adversely influenced the 3-hour postprandial glucose profile (A) and early-phase insulin (C) (gray bar) after the breakfast test meal. In contrast, no such effects occurred in the DMI group (B and D). See Materials and Methods for details on the fasting duration before each breakfast test meal. Data correspond to the mean ± SEM across participants per simulated day/night work condition and per meal timing group (n = 10 in the NMC group and n = 9 in the DMI group).

Fig. 5.. Effects of meal timing intervention on glucose tolerance after the dinner test meal.

The meal timing intervention did not significantly modify the impact of simulated night work on the 3-hour postprandial glucose and the early- and late-phase insulin profiles after the dinner test meal. Simulated night work in both the NMC group (A and C) and the DMI group (B and D) did not affect the 3-hour postprandial glucose and the early- and late-phase insulin profiles after the dinner test meal (see Materials and Methods for details on the fasting duration before each dinner test meal). Data correspond to the mean ± SEM across participants per simulated day/night work condition and per meal timing group (n = 10 in the NMC group and n = 9 in the DMI group).

Fig. 6.. Effects of meal timing intervention on the time course of glucose and insulin.

The meal timing intervention significantly modified the impact of simulated night work on the average values of glucose but not on insulin. Accordingly, simulated night work in the NMC group adversely influenced glucose profile, with overall higher concentrations (A), but not the overall insulin concentrations (C). In contrast, simulated night work in the DMI group did not adversely affect glucose (B) or insulin profiles (D). Data are shown on a 24-hour scale to highlight comparisons between baseline and simulated night work conditions matched by time of day (relative clock time, 7 a.m. as habitual wake time). Data correspond to the average (mean ± SEM) across participants per simulated day/night work condition and per meal timing group (n = 10 in the NMC group and n = 9 in the DMI group).

Fig. 7.. Effects of meal timing intervention on the time course of CBT and cortisol.

The meal timing intervention did not significantly modify the impact of simulated night work on the average values of CBT and cortisol. Accordingly, simulated night work did not significantly impact the overall levels of CBT (A and B) and cortisol (C and D), as compared to baseline, in either group. Results are shown relative to 24-hour clock time, as a proxy for circadian phase. As expected for outputs under strong central circadian control, CBT and cortisol profiles closely followed the 24-hour clock time. Data correspond to the average (mean ± SEM) across participants per simulated day/night work condition and per meal timing group (n = 10 in the NMC group and n = 9 in the DMI group).

Fig. 8.. Conceptual scheme for meal timing effects on internal circadian alignment and glucose tolerance.

In the NMC group (left), there is a misalignment of the fasting/eating cycle (i.e., night eating) and the sleep/wake cycle (i.e., night work) with the central circadian rhythm. This scenario results in (1) internal circadian misalignment across circadian oscillators (illustrated by hypothesized out-of-phase clocks) and with the misalignment of circadian peripheral rhythms (e.g., endogenous circadian glucose and insulin rhythms) relative to the central circadian rhythm (e.g., endogenous circadian CBT rhythm). It also results in (2) impaired glucose tolerance, predicted to occur because of decreased insulin release and insulin sensitivity, thereby causing dysglycemia. In contrast, the DMI group (right) maintains the alignment of the fasting/eating cycle (i.e., day eating) with the central circadian rhythm, despite the misalignment of the sleep/wake cycle (i.e., night work). Consequently, this leads to (1) internal circadian alignment and (2) normalized glucose tolerance. This state of normoglycemia may prevent glucose intolerance in individuals experiencing circadian rhythm disruption, as in the case of night workers.