0002 24-hour Variation in Metabolic Responses to a 6.5-Hour Meal Window in Humans

Abstract Introduction Meal timing influences human health. For example, compared to eating during the day, eating identical meals at night acutely elevates levels of glucose and triglycerides. While most studies have compared single meals given at two distinct (often opposite) times of day, the timecourse of the 24-hour variation in metabolic responses to meals is unknown. The aim of this study was to examine systematically how the timing of meals across the 24-hour circadian cycle influences daily exposure to triglycerides, triglyceride-rich lipoproteins [remnant cholesterol (remnant-C)] and glucose. Methods Ten healthy adults (6 female) aged 22-35 years were randomized to a 16-hour intervention ‘day’ in dim light (< 3 lux) between two 8-h sleep episodes in darkness, with a 6.5-hour meal window in the center of the day scheduled at one of 16 stimulus times distributed every 90-minutes (~22.5 degrees) across the 24-hour day between participants. A 26–48.5-h constant routine (CR) with hourly identical meals preceded the intervention day. Blood samples collected every 20-60 minutes throughout the CR and intervention day were assayed for triglyceride, remnant-C and glucose. The 24-h area under the curve (AUC) of the intervention day was calculated and expressed relative to the first 24-h AUC of the CR to control for interindividual differences in metabolic analyte levels. Mealtime response curves were generated by analyzing the relative AUC by the clock time of meal onset using a single-harmonic sinusoidal regression. Results Significant mealtime response curves were generated for triglycerides (p< 0.05), remnant-C (p< 0.01) and glucose (p< 0.001). The fitted curve for the 24-h AUC showed that daily levels were lowest when eating during daytime hours for triglyceride and remnant -C, which were lowest when eating at ~7pm, and glucose, which was lowest at ~9am. Conclusion The timing of meals across the 24-hour day alters daily exposure to triglycerides, triglyceride-rich lipoproteins, and glucose, with generally worse metabolic responses when the eating window started at night compared to the day. These mealtime response curves can inform practical advice on timing diet-based interventions to reduce cardiometabolic health risks, particularly in shift workers and others who eat at night. Support (if any) Sleep Research Society Career Development Award; R01HL159207