Fasting-induced glucose intolerance is not impacted by the addition of daily exercise: A randomized crossover study

Short-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. KEY POINTS: Short-term fasting reduces insulin sensitivity and glucose tolerance, which manifests as exaggerated glycaemic responses to refeeding. Performing exercise during a fast could mitigate fasting-induced glucose intolerance, due to the well-established insulin-sensitizing effects of acute exercise. Here 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. Exercise appears ineffective in reversing fasting-induced glucose intolerance, which could reflect the mechanistic distinction between fasting-induced and pathological forms of insulin resistance.