0036 Effects of Circadian-Based Early vs Late Dinner on Whole-Body Substrate Metabolism: Preliminary Results from a Randomized Crossover Study

Abstract Introduction Eating at times misaligned with endogenous circadian phase, such as consuming food close to dim light melatonin onset (DLMO) or bedtime increases risk for obesity and diabetes, but the drivers of the adverse metabolic effects are unclear. Using a timed dietary intervention, we evaluated the impact of circadian-misaligned late eating on whole-body substrate oxidation. Methods We are conducting a randomized, cross-over trial to compare DLMO-based early vs late isocaloric dinner on substrate oxidation using whole-room indirect calorimetry (i.e., metabolic chamber) in healthy adults. Participants undergo 2 inpatient stays in a metabolic chamber in random order: (1) early dinner (DLMO-3h); (2) late dinner (DLMO+1h), with an identical 8h sleep opportunity (DLMO+2h to DLMO+10h). The main outcomes include differences in 4h post-dinner area under the curve (AUC) for respiratory quotient (RQ), carbohydrate oxidation, and fat oxidation. As an exploratory outcome, we assess 24h metabolic flexibility, which is the ability to readily shift between fat and carbohydrate utilization in response to feeding or fasting. We defined 24h metabolic flexibility as the difference between the daytime mean RQ and sleep RQ. We used signed rank tests to compare between the conditions. Results To date, 10 healthy participants have completed the study (9 female, 1 male, mean (SD) age 24.9 (2.7) years, BMI 21.3 (1.1) kg/m²). Compared to early dinner, late dinner reduced post-dinner RQ by 0.12 [0.04] or 3.7 [1.2] % (median [IQR]; P=0.002) and carbohydrate oxidation by 0.19 [0.08] g/min or 28.2 [9.7] % (P=0.002). Furthermore, 24h metabolic flexibility was reduced with late dinner (P< 0.001), indicating blunted fuel switching between carbohydrate and fat. Conclusion Our preliminary findings reveal that eating after DLMO alters post-dinner fuel utilization patterns, characterized by reduced carbohydrate oxidation and metabolic flexibility. These results provide novel insights into how misalignment between meal timing and circadian rhythms may contribute to the development of type 2 diabetes. Support (if any) K23DK133690, 1ZIADK075176, AASM 273-BS-22, R01HL135483,