["The Journal of Physiology, EarlyView. ", "\nAbstract figure legend In a randomized crossover design 16 healthy young adults performed a 48‐h fast with or without the addition of daily cycling (50‐min moderate‐intensity continuous training (MICT) + 5×1‐min high‐intensity interval training (HIIT)) at baseline and 24 h into the fast. Glycaemic responses to a mixed meal tolerance test (MMTT) were assessed before and after the fast. As expected fasting elicited a significant reduction in glucose tolerance, which was unaffected by the addition of daily exercise. Exploratory sex difference analyses suggested glucose tolerance was impaired to a greater extent after fasting in females compared to males.\n\n\n\n\n\n\n\n\n\nAbstract\nShort‐term fasting (48–72 h) impairs insulin sensitivity and glucose tolerance, but it is unclear if aerobic exercise – which is known to have insulin‐sensitizing effects – can attenuate fasting‐induced decrements in glucose homeostasis. To determine whether the addition of exercise to a short‐term fast impacts glycaemic responses to refeeding, we implemented a randomized crossover design where 16 healthy adults (8 males and 8 females, 24±4 years) fasted for 48 h with and without the addition of daily cycling (50‐min moderate‐intensity continuous training + 5×1‐min high‐intensity interval training) performed at baseline and 24 h into the fast. Glycaemic responses to a mixed meal tolerance test (MMTT) were assessed via capillary measurements and continuous glucose monitoring (CGM) before and after the fast, as well as 24 h after refeeding. Capillary glucose and CGM incremental area under the curve (iAUC) during the 2‐h mixed meal tolerance test increased at 48 h fasted relative to baseline (P<0.001), which was unaffected by the addition of exercise (condition × time interaction, P>0.364). The 2‐h CGM iAUC reduced 24 h after refeeding compared to 48 h fasted (with or without exercise, P<0.001) but remained elevated relative to baseline (P = 0.01). Exploratory analyses revealed that 2‐h capillary (P = 0.020) and CGM (P<0.001) glucose iAUC and plasma glucose (P<0.001) were elevated to a greater extent after refeeding in females compared to males, and females exhibited greater impairments in CGM metrics in the 24 h after refeeding (P<0.01). Our results suggest that combined moderate‐intensity continuous training and high‐intensity interval training exercise does not attenuate fasting‐induced perturbations in glucose homeostasis and that glucose intolerance persists 24 h after refeeding.\n\n\n\n\n\n\n\n\n\nKey points\n\nShort‐term fasting reduces insulin sensitivity and glucose tolerance, which manifests as exaggerated glycaemic responses to refeeding.\nPerforming exercise during a fast could mitigate fasting‐induced glucose intolerance, due to the well‐established insulin‐sensitizing effects of acute exercise.\nHere we report that a 48‐h fast performed with or without the addition of daily aerobic exercise similarly impaired glucose tolerance upon refeeding and resulted in comparable decrements in continuous glucose monitoring–derived metrics of glycaemic regulation over the 24 h after refeeding.\nExercise appears ineffective in reversing fasting‐induced glucose intolerance, which could reflect the mechanistic distinction between fasting‐induced and pathological forms of insulin resistance.\n\n\n"]