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

项目总结/摘要 新发布的指南建议增加体力活动（PA），减少久坐行为 (SB)2型糖尿病（T2 D）的发病和进展。通常，30-60 主张每天最少PA发作。虽然这种方法增加了PA，但它不会减少长度 一天中久坐不动的时间这一点很重要，因为最近的流行病学数据表明， 经常中断久坐时间可以改善血糖控制，即使是那些达到 建议的PA水平。我们的初步实验数据表明，打破长时间的久坐不动， 通过全天进行多次短时间PA（5分钟），可以改善睡眠质量， 进行PA的单次连续回合，从而可能是预防T2 D的新策略。的 即使当PA总量和总能量消耗为 匹配，这表明如何以及何时进行PA可能比PA多少更重要 完成了然而，重要的知识差距仍然包括：（1）是否类似的好处，对葡萄糖 在患有前驱糖尿病的成年人中观察到控制，这是一个临床相关的人群， 发展T2 D;（2）这些影响是否持续或随着时间的推移而减弱，以及（3） 基础为了解决这些差距，我们建议测量PA中断的急性和慢性影响 对血糖控制和潜在的机制在发展中国家T2 D的风险的个人。久坐的男性 超重或肥胖和糖尿病前期的女性（n=66，50% F）将被随机分配到 干预设计为中断SB，每天9小时，每小时进行一次5分钟的快走，5 天/周（BREAK）或对照条件，包括每天进行45分钟的快走， 连续发作，5天/周（一次）。根据我们的初步数据，我们假设， BREAK对血糖控制的作用可能与胰岛素敏感性的更大改善无关， 其他机制包括葡萄糖流量的变化。我们假设由于持续时间短 在运动回合中，BREAK优先依赖肌糖原来满足能量需求。因此，在本发明中， 血浆葡萄糖在每次活动后被肌肉吸收以补充糖原储存。来 日，餐后血糖将减少，因为增加了膳食葡萄糖的摄取。相比之下， 有一种情况会优先依赖脂肪作为燃料，对每日血糖波动的益处较少。测试 这一假设，每日血糖波动，全身胰岛素敏感性，内源性和外源性葡萄糖 动力学和参与碳水化合物代谢调节的骨骼肌分子途径， 胰岛素作用将使用我们最先进的金标准临床和分子方法进行测量 住院设施。这项研究将开始，以建立长期有益的健康影响，打破SB 并可能对控制血糖以预防T2 D的策略产生新的见解。

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.