Breaking up sedentary behaviors to improve glucose control in a population at risk for developing type 2 diabetes

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PROJECT SUMMARY/ABSTRACT Newly released guidelines recommend increased physical activity (PA) and reduced sedentary behaviors (SB) to improve glycemia and prevent the onset and progression of type 2 diabetes (T2D). Typically, 30-60 min bouts of PA are advocated per day. Although this approach increases PA, it does not decrease the length of the sedentary periods through the day. This is important because recent epidemiological data suggest that frequently interrupting sedentary time improves glucose control even in people who achieve the recommended levels of PA. Our preliminary experimental data suggest that breaking up prolonged sedentary time by performing multiple short bouts (5 min) of PA throughout the day, may improve glycemia more than performing a single continuous bout of PA, and thereby potentially be a novel strategy to prevent T2D. The improvement in glycemia was observed even when the total amount of PA and total energy expenditure were matched, suggesting that how and when PA is performed over the day may matter more than how much PA is done. However, important gaps in knowledge remain including: (1) whether similar benefits on glucose control would be observed in adults with prediabetes, a clinically relevant population that is at high risk of developing T2D; (2) whether these effects are sustained or diluted over time, and (3) what are the mechanistic underpinnings. To address these gaps, we propose to measure the acute and chronic effects of PA breaks on glucose control and the underlying mechanisms in individuals at risk of developing T2D. Sedentary men and women with overweight or obesity and prediabetes (n=66, 50% F) will be randomized to either an intervention designed to interrupt SB with 5-min bouts of brisk walking performed hourly for 9 hours/day, 5 days/week (BREAK) or a control condition consisting of 45-min of brisk walking performed as a single daily continuous bout, 5 days/week (ONE). Based on our preliminary data, we hypothesize that the greater benefits of BREAK on glucose control may not be associated with greater improvement in insulin sensitivity but with other mechanisms including changes in glucose fluxes. We hypothesize that because of the short duration of exercise bouts, BREAK preferentially relies on muscle glycogen to meet energy demand. As a result, plasma glucose is taken up by muscles to replenish glycogen stores following each active bout. Over the day, postprandial glycemia will be reduced because of increased uptake of meal glucose. By contrast, the ONE condition will preferentially rely on fat as fuel and has less benefit on daily glucose excursions. To test this hypothesis, daily glucose excursions, whole-body insulin sensitivity, endogenous and exogenous glucose kinetics, and skeletal muscle molecular pathways involved in the regulation of carbohydrate metabolism and insulin action will be measured using gold standard clinical and molecular methods in our state-of-the-art inpatient facility. The study will begin to establish the long-term beneficial health effects of breaking up SB and may lead to new insights on strategies to control glucose to preventT2D.