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

项目摘要/摘要 新发布的指南建议增加体力活动(PA)和减少久坐行为 (Sb)改善血糖，预防2型糖尿病(T2D)的发生和发展。通常为30-60 建议每天服用至少一次PA。虽然这种方法增加了PA，但它不会减少长度 一整天的久坐时间。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，即使是在达到 PA的推荐量。我们的初步实验数据表明，打破久坐不动 通过全天进行多次短时间的PA(5分钟)，可能会更好地改善血糖 进行一次连续的PA比赛，从而潜在地成为预防T2D的一种新策略。这个 即使在PA总量和总能量消耗 相匹配，这表明一天中如何以及何时进行PA可能比PA多少更重要 已经完成了。然而，知识上的重要差距仍然包括：(1)对葡萄糖是否有类似的益处 在患有糖尿病前期的成人中观察对照，这是一个临床相关的人群，有很高的患病风险 发展T2D；(2)随着时间的推移，这些影响是持续的还是被稀释的；(3)机制是什么 支撑点。为了解决这些差距，我们建议衡量PA中断的急性和慢性影响 有发生T2D风险的个体的血糖控制和潜在机制。久坐不动的男人 超重或肥胖并有糖尿病前驱症状的女性(n=66，50%女性)将被随机分为 为打断某人而设计的干预措施是每小时进行5分钟的快步行走，每天9小时 天/周(休息)或由45分钟快走组成的对照条件作为每天进行 连续比赛，5天/周(1次)。根据我们的初步数据，我们假设更大的好处 血糖控制的中断可能与胰岛素敏感性的更大改善无关，而是与 其他机制包括葡萄糖通量的变化。我们假设由于持续时间较短 在运动比赛中，Break优先依赖肌肉糖原来满足能量需求。结果, 每一场比赛后，肌肉都会吸收血糖，以补充糖原储备。超过了 一天后，餐后血糖会降低，因为餐后葡萄糖摄取增加。相比之下， 其中一种情况将优先依赖脂肪作为燃料，对每日葡萄糖漂移的益处较小。为了测试 这一假说，每日血糖漂移、全身胰岛素敏感性、内源性和外源性葡萄糖 运动学和骨骼肌分子通路参与调节碳水化合物代谢和 在我们最先进的技术中，将使用黄金标准的临床和分子方法来测量胰岛素的作用 住院部。这项研究将开始确定拆散某人对健康的长期有益影响 并可能导致对控制血糖以预防T2D的策略的新见解。

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.