Diurnal differences in postprandial glucose and triglyceride metabolism reveal metabolic flexibility and resilience

The study investigated the diurnal variance in metabolic resilience (i.e., the robustness, the recovery, and reorientation of metabolism) and metabolic flexibility in glucose and fat oxidation rates to three identical test meals. Eight young, healthy subjects consumed identical liquid mixed meals three times a day (33% of energy requirement each), followed by a defined bout of physical activity conducted in a whole room indirect calorimeter to continuously assess energy expenditure and postprandial changes in substrate oxidation rates as a measure of metabolic flexibility. A mathematical metabolic resilience model was used to analyze the postprandial blood parameters. Throughout the day, postprandial glucose area under the curve (AUC) increased (means ± SD, breakfast 17.3 ± 2.4 vs. dinner 20.8 ± 2.0 g/180 min; <i>P</i> < 0.001), whereas triglyceride AUC decreased (breakfast 434 ± 158 vs. dinner 365 ± 104 mg/180 min; <i>P</i> = 0.039) at identical insulin AUC and energy balance. Fat oxidation increased from breakfast 24.8 ± 8.7 to dinner 28.0 ± 8.7 g/180 min (<i>P</i> = 0.029), whereas the respiratory exchange ratio declined from 0.035 ± 0.026 to 0.012 ± 0.029 (<i>P</i> = 0.005). The metabolic resilience model reveals a diurnal increase in the rate of lipolysis of circulating triglycerides at a concomitant decrease in the rate of exogenous and endogenous triglyceride appearance. Meal-to-meal changes in glucose AUC indicate rising insulin resistance during the day. However, this reflects a resilient metabolism that shifts to triglyceride metabolism in the evening while maintaining insulin AUC and energy balance.<b>NEW & NOTEWORTHY</b> Conventionally, postprandial tests have focused exclusively on glucose metabolism. The integration of a mixed meal computational model with substrate oxidation rates facilitates the assessment of the interplay between glucose and lipid metabolism, thereby determining metabolic resilience under physiological conditions. Throughout the day, metabolic resilience is characterized by increased triglyceride lipolysis with a decreased rate of triglyceride appearance from the gut and an increased basal rate of endogenous triglycerides from the liver, whereas metabolic flexibility decreases.