Introduction: Although glucose tolerance in healthy individuals is higher in the morning vs. evening, the potential role of the endogenous circadian system, independent of light-dark and behavioral (e.g., sleep, eating) cycles, has not been tested using a gold-standard circadian protocol. Furthermore, it is unclear whether such endogenous circadian rhythm in glucose tolerance can be synchronized by prior eating times in humans. In addition, there is a clear knowledge gap in circadian influences on postprandial insulin responses, in particular early-phase insulin as a measure of pancreatic beta-cell function. We tested the hypotheses that there exists an endogenous circadian rhythm in glucose tolerance and early-phase insulin, and that these rhythms can be phase-shifted by a prior history of delayed mealtimes. Methods: In a randomized crossover trial, 16 adults with overweight/obesity and without diabetes (11 men, age 37±11 y, BMI 28.8±2.4 kg·m-2, HbA1c 5.4±0.4 %; mean±SD) completed two 8-day in-laboratory protocols: an early eating (EE, 4 days) and a late eating (LE, 4 days) condition, in random order and including a washout. Each condition was preceded by a 5-day EE baseline and followed by a Constant Routine (CR) procedure. Both protocols were identical for behavioral (sleep, physical activity, posture) and environmental (lighting, temperature) conditions and timing. Three identical test meals were consumed 4h:10m apart, with all meals delayed by 4h:10m in LE vs. EE. We then assessed the endogenous circadian rhythmicity in glucose tolerance using 36-h CR protocols (i.e., continuous wakefulness, semi-recumbent posture, dim light, and test meals every 6h) to isolate the endogenous circadian glucose and insulin responses. Using the last five of six CR test meals, glucose tolerance and early-phase insulin were quantified from 3-h postprandial incremental area under the curves (iAUCs) of serum glucose concentrations and first 30-min of serum insulin concentrations, respectively. Individual endogenous circadian phase was derived from core body temperature (CBT) measurements made throughout the CR. Circadian rhythm phase and amplitude of main outcomes was derived from cosinor analysis of normalized (across circadian cycle) iAUC using mixed model analyses of variance. Results: There was no difference in the timing of CBT nadir after EE and LE (p>0.05). The peak-to-trough amplitudes in normalized 3-h postprandial glucose and 30-min early-phase insulin iAUC were 36% (p< 0.001) and 32% (p=0.016) of the mean across circadian cycle, respectively, after EE, with the highest and lowest glucose tolerance (~5 AM/~5 PM) and early-phase insulin response (~7 AM/~7 PM) in the biological morning and evening, respectively. After LE, the peak-to-trough amplitudes in normalized 3-h postprandial glucose and 30-min early-phase insulin iAUC were 35% (p< 0.05) and 39% (p=0.001) of the mean across circadian cycle, respectively, with a significant phase delay in i) glucose tolerance by ~60° (~4h; circadian rhythm-protocol interaction p< 0.05), and ii) early-phase insulin by ~90° (~6h; rhythm-protocol interaction p=0.002). Conclusion: Our findings demonstrated in people with overweight or obesity that glucose tolerance and early-phase insulin expressed a robust endogenous circadian rhythm in glucose tolerance and early-phase insulin that peaks in the biological morning and reaches a trough in the evening. Notably, this study revealed a gradual decoupling of central (core body temperature) and peripheral (glucose and insulin) circadian rhythms, by demonstrating a synchronization of glucose and insulin rhythmicity to eating schedules, with no change in central rhythmicity, over four days. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Koh et al. (Fri,) studied this question.