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)会增加肥胖和代谢性疾病、认知缺陷以及 在一生中影响疾病。这些都是关键的结果，因为有这些危险因素的儿童更容易 有可能患上2型糖尿病(T2 DM)。SB通过促进高血糖和增加T2 DM的风险 更大的餐后血糖变异性以及通过认知障碍和抑郁症状导致 能量平衡不良行为、肥胖和恶化的胰岛素抵抗。体力活动可以减少这些 风险因素，然而，只有不到一半的美国年轻人达到指南建议，并且体育活动仍在继续 在整个青春期都在衰退。因此，迫切需要测试替代干预方法，以 预防儿童2型糖尿病的持续运动。我们是第一个展示这种干扰的 短时间3分钟的适度运动可以改善糖耐量和消极情绪。 3个小时的会议。然而，目前尚不清楚这些短期改善是否会转化为持续的多天。 有益于新陈代谢、认知和情绪结果。因此，这项研究的总体目标是测试 干预SB作为超重/肥胖青年T2 DM预防策略的多日效应。我们建议 一项第二阶段随机对照试验，比较SB干扰和持续运动对长时间坐着的影响 7-11岁超重/肥胖儿童。这项建议将解决以下目标：(1)确定 用连续血糖监测仪和动态血糖监测仪测定静坐干预血糖稳态的多天疗效 口服葡萄糖耐量试验；(2)测定中断久坐对认知功能的多日疗效 改善；以及(3)确定打断坐着情绪和焦虑改善的多天有效性。 这项研究具有创新性，因为：(A)干扰某人是一种新的干预策略，已显示出潜在的 显著改善新陈代谢参数，但长期影响尚不清楚，之前的研究也没有 比较使用该方法与单次锻炼在降低多种T2 DM危险因素方面的有效性 (B)使用连续血糖监测是一种新的策略，可以调查多个 日间血糖对SB干扰的反应及其与认知和情感结果的关联；以及(C) 研究多天打断某人与单次锻炼时的心理反应是新奇的 结果在一天中都是不同的，并且对于阐明我们是否要开发新的干预措施是必不可少的 处理与T2 DM风险相关因素的方法。鉴于血糖动态平衡的改善 我们的急性3小时试验，以及调查持续干预中断的儿科研究的缺乏 SB，这项研究是测试这种方法的有效性的重要和合乎逻辑的下一步 超重/肥胖儿童中的多种2型糖尿病危险因素。我们的方法很有影响力，因为严格的、 受控的实验室设置将使我们能够为儿童设计更强大的干预策略，这些策略可以转化为 其他环境，以及年龄和体重组，从而有助于降低美国青年中T2 DM的风险。

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.