Testing the efficacy of multi-day interruptions in sedentary behaviors on metabolic, cognitive, and affective outcomes in youth at risk for Type 2 diabetes

摘要 久坐行为（SB）有助于增加肥胖和代谢疾病，认知缺陷， 影响整个生命周期的疾病。这些结果至关重要，因为有这些风险因素的儿童 2型糖尿病（T2 DM）的发病机制SB通过促进高血糖增加T2 DM风险， 更大的餐后血糖变异性以及通过认知障碍和抑郁症状， 不良的能量平衡行为、肥胖和胰岛素抵抗恶化。体力活动可以减少这些 风险因素，但只有不到一半的美国青年符合指南建议， 在整个青春期下降。因此，迫切需要测试替代干预方法， 持续运动以预防儿童T2 DM。我们是第一个证明 SB与短期，3分钟，适度运动的发作改善了葡萄糖耐量和消极情绪，在一个单一的 3-小时会议。然而，目前尚不清楚这些短期改善是否会转化为持续多日的改善。 有益于代谢、认知和情绪结果。因此，本研究的总体目标是测试 在超重/肥胖青年中中断SB作为T2 DM预防策略的多日效应。我们提出 一项II期RCT，旨在比较SB中断与持续运动和长时间静坐的影响。 7-11岁超重/肥胖儿童。本提案将实现以下目标：（1）确定 通过连续血糖监测仪测量的中断坐位对葡萄糖稳态的多日疗效， 口服葡萄糖耐量试验;（2）确定中断坐着对认知功能的多日疗效 改善;（3）确定中断坐在情绪和焦虑改善上的多日功效。 这项研究是创新的，因为：（a）中断SB是一种新的干预策略，已显示出潜力， 急性改善代谢参数，但长期影响是未知的，没有先前的研究 比较了使用这种方法与单次运动在降低多种T2 DM风险因素方面的疗效， （B）使用连续葡萄糖监测是一种新的策略，以研究多天， 对SB中断的日血糖反应及其与认知和情感结果的关联;以及（c） 研究连续多日中断SB与单次运动的心理反应是新颖的 这些结果在一天中会发生变化，如果我们要开发新的干预措施， 解决与T2 DM风险相关因素的方法。鉴于葡萄糖稳态的改善， 我们的急性3小时试验，沿着缺乏儿科研究调查持续干预中断 SB，这项研究是一个重要的和合乎逻辑的下一步，以测试这种方法的有效性，为减少 超重/肥胖儿童中的多种T2 DM风险因素。我们的方法是有影响力的，因为严格， 受控的实验室设置将使我们能够为儿童设计更强有力的干预策略， 其他环境，年龄和体重组，从而有助于降低美国青年T2 DM风险的努力。

ABSTRACT Sedentary behavior (SB) contributes to increased risk for obesity and metabolic disease, cognitive deficits, and affect disorders over the lifespan. These are critical outcomes because children with these risk factors are more likely to develop type 2 diabetes mellitus (T2DM). SB increases T2DM risk by promoting hyperglycemia and greater postprandial glycemic variability as well as via cognitive detriments and depressive symptoms that lead to poor energy balance behaviors, obesity, and worsening insulin resistance. Physical activity can reduce these risk factors, however less than half of US youth meet guideline recommendations, and physical activity continues to decline throughout adolescence. Thus, there is a critical need to test alternative intervention approaches to sustained bouts of exercise for the prevention of T2DM in children. We were the first to show that interrupting SB with short, 3-minute, bouts of moderate exercise improved glucose tolerance and negative mood in a single 3-hour session. However, it is unknown whether these short-term improvements translate to sustained multi-day benefits to metabolic, cognitive, and mood outcomes. Thus, the overall goal of this study is to test the efficacy of multi-day effects of interrupting SB as a T2DM prevention strategy in youth with overweight/obesity. We propose a Phase II RCT to compare the effects of SB interruptions vs. sustained bouts of exercise to prolonged sitting in 7-11-year-old children with overweight/obesity. This proposal will address the following aims: (1) determine the multi-day efficacy of interrupting sitting on glucose homeostasis measured by continuous glucose monitor and oral glucose tolerance tests; (2) determine the multi-day efficacy of interrupting sitting on cognitive function improvements; and (3) determine the multi-day efficacy of interrupting sitting on affect and anxiety improvements. This study is innovative because: (a) interrupting SB is a novel intervention strategy that has shown potential to acutely improve metabolic parameters, yet the longer-term effects are unknown and no prior studies have compared efficacy in reducing multiple T2DM risk factors using this approach vs. a single bout of exercise over multiple days in children; (b) the use of continuous glucose monitoring is a novel strategy to investigate multi- day glucose responses to SB interruptions and their association with cognitive and affective outcomes; and (c) investigating psychological responses to multiple days of interrupting SB vs. a single bout of exercise are novel outcomes that co-vary throughout the day, and are essential to elucidate if we are to develop novel intervention approaches that address factors associated withT2DM risk. Given the improvements in glucose homeostasis in our acute 3-hour trials, along with the dearth of pediatric studies investigating sustained interventions interrupting SB, this study is a significant and logical next step towards testing the efficacy of this approach for the reduction of multiple T2DM risk factors in children with overweight/obesity. Our approach is impactful because the rigorous, controlled lab setting will allow us to design stronger intervention strategies for children that can be translated to other settings, and age and weight groups, thereby contributing to efforts at reducing T2DM risk in U.S. youth.