Effects of early vs. late time restricted eating vs. daily caloric restriction on weight loss and metabolic outcomes in adults with obesity

项目总结 这项建议的目标是确定产生减肥效果的最佳限时进食(TRE)窗口 对于超重或肥胖的成年人。每日卡路里限制(DCR)，当前的护理标准饮食策略 对于减肥，在基于指南的行为减肥计划的背景下，产生5%-7%的体重减轻， 然而，坚持下去是具有挑战性的，体重恢复是很常见的。因此，严格评估该方案的有效性 需要新的饮食干预措施来提供一系列以证据为基础的选择来有效地治疗 肥胖。Tre涉及将能量摄入(EI)限制在每天有限的时间窗口内，并已被广泛应用 在业馀媒体上推广，但到目前为止，Tre研究表明体重只有很小的下降(0-4%)。然而，之前 TRE研究有几个实质性的限制，包括缺乏护理标准的DCR对照组，小 样本量大，持续时间短，以及未能提供基于行为的适当肥胖治疗指南 支持。虽然可以使用几种不同的饮食策略来实现能量限制，但行为支持 对于加强对饮食和体力活动(PA)建议的遵守，从而减肥至关重要 结果，但之前没有研究为TRE提供行为支持。此外，迄今为止大多数TRE研究 我利用了较晚的时间窗口(L-时间，例如，晚上12点到8点的就餐窗口)，经常提供这样的理由 参与者更有可能坚持L-tre，而不是早期的tre(E-tre，即上午8点至下午4点的就餐窗口)。 然而，机械学研究表明，E-Tre可能会导致更大的减肥效果 且对心脏代谢的益处优于L-特雷。我们已经证明，E-Tre可以改善血糖 变异性和胰岛素敏感性，临床显著体重减轻(12周时为6.3±4.1%)，以及 饮食质量的改善，增加的PA，减少的久坐时间和主观上的改善 睡吧。然而，我们没有包括L-tre控件，因此不清楚是E-tre窗口还是条款 与先前的TRE研究相比，行为支持的结果增强了减肥效果。因此，一个严格的 需要设计试验来评估E-TRE、L-TRE和DCR在 基于指南的行为干预对体重减轻和心脏代谢结果的影响。在这项研究中，162名成年人 超重或肥胖的患者将以1：1：1的比例随机分配到E-Tre(从醒来后1-2小时开始的8小时窗口)，L-Tre (唤醒后5-6小时开始的8小时窗口)或DCR(25%热量限制)26周(主要结果)， 随访52周。我们的目的是比较E-Tre、L-Tre和DCR在以下方面的影响：1)身体变化 体重和心脏代谢健康的成分和标志物；2)饮食依从性、EI和饮食质量；以及 3)PA和睡眠。我们的总体假设是，E-Tre将导致更大的体重减轻和改善 心脏代谢结果与L-Tre相比，将不会低于我们目前的护理标准(DCR)。 此外，我们假设对E-Tre和L-Tre的坚持将大于对DCR的坚持，并且E-Tre-Tre将超过对DCR的坚持。 与L-Tre和DCR相比，Tre将导致对PA的更大依从性和更好的睡眠持续时间/质量。

PROJECT SUMMARY The goal of this proposal is to determine the optimal time restricted eating (TRE) window to produce weight loss in adults with overweight or obesity. Daily caloric restriction (DCR), the current standard of care dietary strategy for weight loss, produces 5-7% weight loss in the context of a guidelines-based behavioral weight loss program, yet adherence is challenging and weight regain is common. Thus, rigorous evaluation of the effectiveness of novel dietary interventions is needed to provide a range of evidence-based options to effectively treat obesity. TRE involves restriction of energy intake (EI) to a limited window of time each day and has been widely promoted in the lay press, but TRE studies to date have shown only minimal (0-4%) weight loss. However, prior TRE studies have several substantial limitations, including lack of standard of care DCR control groups, small sample sizes, short duration, and failure to provide appropriate obesity treatment guidelines-based behavioral support. While several different dietary strategies can be used to achieve energy restriction, behavioral support is critical to enhancing adherence to both diet and physical activity (PA) recommendations and thus weight loss outcomes, yet no prior studies have provided behavioral support for TRE. Further, most TRE studies to date have utilized late TRE windows (L-TRE, e.g., eating window 12-8 PM), often providing the rationale that participants are more likely to adhere to L-TRE rather than early TRE (E-TRE, e.g. eating window 8AM-4PM). However, there is strong rationale from mechanistic studies to suggest E-TRE may result in greater weight loss and cardiometabolic benefits than L-TRE. We have shown that E-TRE results in improvements in glucose variability and insulin sensitivity, clinically significant weight loss (6.3 ± 4.1% at 12 weeks), as well as improvements in dietary quality, increased PA, reduced sedentary time and subjective improvements in sleep. However, we did not include a L-TRE control, so it is unclear whether the E-TRE window or the provision of behavioral support enhanced weight loss outcomes as compared to prior TRE studies. Thus, a rigorously designed trial is needed to evaluate the impact of E-TRE, L-TRE and DCR delivered in the context of a guidelines-based behavioral intervention on weight loss and cardiometabolic outcomes. In this study, 162 adults with overweight or obesity will be randomized 1:1:1 to E-TRE (8-hr window starting 1-2 hrs after waking), L-TRE (8-hr window starting 5-6 hrs after waking) or DCR (25% caloric restriction) for 26 weeks (primary outcome), with follow up at 52 weeks. Our aims are to compare the effects of E-TRE, L-TRE, and DCR on: 1) Changes in body weight and composition and markers of cardiometabolic health; 2) Dietary adherence, EI and dietary quality; and 3) PA and sleep. Our overall hypothesis is that E-TRE will result in greater weight loss and improvements in cardiometabolic outcomes as compared to L-TRE and will be non-inferior to our current standard of care (DCR). In addition, we hypothesize that adherence to E-TRE and L-TRE will be greater than adherence to DCR, and E- TRE will result in greater adherence to PA and improved sleep duration/quality as compared to L-TRE and DCR.