Abstract

A consistent and robust body of research shows that physical activity benefits the management of type 2 diabetes both acutely (by increasing muscle glucose uptake during and after exercise) and habitually (by enhancing in-ulin sensitivity, mitochondrial function, and lipid metabolism). Total energy expended is important, but repeated high-intensity activity enhances insulin sensitivity and confers metabolic benefits exceeding expectations based on the energy expended. Reducing sedentary behaviour by breaking up sitting with frequent bouts of activity similarly opposes insulin resistance and increases glucose uptake even with modest energy expenditure, suggesting that repeated “on-off” cycles may be important, but the underlying mechanisms are not well characterized. The dietary, sleep/circadian, and pharmacologic contexts in which exercise takes place are important modulators of exercise effects with potential to accentuate (energy deficit, carbohydrate restriction, adequate sleep and timing of exercise to circadian clocks, hints that GLP1 agonists may potentiate) or blunt (energy excess, high carbohydrate intake, mistiming exercise with circadian clocks, inadequate sleep, addition of metformin or SGLT2 inhibitors) the beneficial effects of acute exercise and habitual physical activity. Studying the interplay between exercise and these factors at the cell/molecular level through the whole-organism levels is necessary to understand critical mechanisms and optimally apply exercise as therapy for type 2 diabetes.