Stand Up for Your Health: A Randomized Study

摘要：随着“在家工作”的扩大，久坐行为变得越来越普遍 文化，最近是由COVID-19大流行推动的。我们现在坐着的时间比其他任何时候都多。 活动结合起来。这增加了椅子的依赖性，包括职业能源消耗的减少 在过去的50年里，导致了慢性疾病的流行，包括代谢综合征， 心血管疾病和2型糖尿病（T2 DM）。几项研究，包括一项大型荟萃分析 在18项研究中，共有794，577名受试者，得出的结论是久坐行为介导了2型糖尿病。CDC预测， 如果目前的趋势继续下去，到2050年，多达三分之一的美国成年人可能患有糖尿病。目前，9%和 34%的美国成年人分别患有T2 DM和前驱糖尿病。虽然我们在初步研究中排除了糖尿病患者， 15名超重或肥胖受试者中有11名在基线时通过HOMA-IR发现有一定的胰岛素抵抗 (BMI与T2 DM的发病率正相关）。在我们对15名久坐办公室的受试者进行的初步研究中， 工作，6个月的坐-站办公桌使用导致胰岛素抵抗改善23%，其中最显著的是 那些每天减少坐着超过90分钟的人。血管内皮细胞的其他改善 观察到功能和甘油三酯水平，而运动活动、步数或体重没有任何变化。 这些发现不仅证实了关于这一主题的流行病学研究结果，而且提出了因果关系， 随机对照试验。这种用坐立两用办公桌取代坐立办公桌的策略具有巨大的潜力， 降低70%被归类为超重或肥胖的成年人的心脏代谢风险，其中大多数人 胰岛素抵抗这种干预可能会产生巨大的影响，并因COVID-19而扩大 鉴于近80%的美国工作都是久坐不动的。我们假设，成年受试者的风险， 糖尿病将改善胰岛素敏感性，代谢和血管（内皮）健康与坐立办公桌 在工作中的干预（无论是在办公室还是在家里），在随机对照试验的背景下。 我们将198名BMI≥25的久坐办公室工作人员以1：1：1的比例随机分为三组： (a)坐-站书桌干预，目标是每天站立2小时;（B）坐-站书桌干预，目标是3小时 （c）对照组超过6个月。坐和站的时间的客观量化将是 使用复杂的活动监视器和智能手机活动日志执行。我们将确定如果坐站 办公桌改善胰岛素敏感性和代谢健康，以及是否存在剂量依赖关系， 久坐时间的变化（目标1）。我们将确定干预是否改善血管内皮功能 局部（股浅动脉FMD）和/或全身（评估肱动脉FMD弹性）（目标2）。 子目标将评估循环甘油三酯和游离脂肪酸水平的变化，并与 内皮功能肯定的调查结果将通过表明一个易于采用的 工作场所的干预只集中在减少坐着的时间，减少心脏代谢的风险。

Abstract: Sedentary behavior is becoming increasingly prevalent with the expansion of a ‘work from home’ culture, most recently driven by the COVID-19 pandemic. We now spend more time sitting than in all other activities combined. This increased chair dependency, including a reduction in occupational energy expenditure over the past 5 decades, has contributed to the epidemic of chronic disease, including metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Several studies, including a large meta-analysis of 18 studies totaling 794,577 subjects, concluded that sedentary behavior mediates T2DM. The CDC predicts that if current trends continue, as many as 1 in 3 U.S. adults could have diabetes by 2050. At present, 9% and 34% of U.S. adults have T2DM and prediabetes, respectively. Although we excluded diabetics in our pilot study, 11 of the 15 overweight or obese subjects were found to have some insulin resistance by HOMA-IR at baseline (BMI positively correlates with the incidence of T2DM). In our pilot study of 15 subjects with sedentary office jobs, 6 months of sit-stand desk use resulted in a 23% improvement in insulin resistance, most substantial in those who decreased daily sitting by over 90 minutes/day. Additional improvements in vascular endothelial function and triglyceride levels were seen without any change in exercise activity, step counts, or body weight. These findings not only corroborate epidemiologic findings on this topic but suggest causality and warrant a randomized control trial. This strategy of replacing sitting desks with a sit-stand desk has significant potential to reduce cardiometabolic risk in the 70% of adults categorized as overweight or obese, the majority of whom have insulin resistance. This intervention could have substantially strong impact, amplified by the COVID-19 pandemic, given nearly 80% of U.S. jobs are sedentary. We hypothesize that adult subjects at-risk for diabetes will improve insulin sensitivity, metabolic and vascular (endothelial) health with a sit-stand desk intervention at work (whether in the office or at home), in the context of a randomized, controlled trial. We will randomize 198 sedentary office workers with a BMI≥25 at risk for T2DM in a 1:1:1 ratio of three groups: (a) sit-stand desk intervention targeting 2 hours standing per day; (b) sit-stand desk intervention targeting 3 hours standing per day; or (c) control arm over 6 months. Objective quantification of sitting and standing times will be performed with sophisticated activity monitors and smartphone activity logs. We will ascertain if the sit-stand desk improves insulin sensitivity and metabolic health and whether there is a dose-dependent relationship with changes in sedentary time (Aim 1). We will determine if the intervention improves vascular endothelial function locally (superficial femoral artery FMD) and/or systemically (assessing brachial artery FMD resilience) (Aim 2). Sub-aims will assess changes in circulating triglycerides and free fatty acid levels and correlate with changes in endothelial function. Affirmative findings would move the field forward by demonstrating that a readily adoptable workplace intervention focused only on reducing sitting time alone, reduces cardiometabolic risk.