Effect of Time-Restricted Feeding on 24-hour Glycemic Control, Blood Pressure, and Cardiovascular Disease Risk Factors in Adults with Prediabetes

项目总结 越来越多的证据表明，虽然不良的进餐时间会导致心脏代谢性疾病，但优化饮食 时机可能会逆转这一点。限时进食是一种新型的间歇性禁食，包括进食 在≤10小时内，然后是≥每天14小时的禁食。对啮齿动物的研究报告TRF改善血糖 控制，降低胰岛素水平，降低肝脏脂肪，预防高脂血症，减少中风后的脑梗塞体积， 并改善与全天进食相关的炎症标志物。重要的是，扶轮基金会的影响可能 取决于食物摄入量的昼夜节律。以前的TRF人体试验将食物摄入量限制在中等水平 白天(中午)的TRF报告了积极的结果，而将食物摄入量限制在当天晚些时候的试验 报告的结果为空或否定。在这些研究的基础上，我们最近进行了TRF的第一次临床试验 其中食物摄入量限制在白天早期(早期TRF)，并发现早期TRF的五周 改善糖尿病前期男性的胰岛素敏感性、β细胞反应性、血压和氧化应激- 即使食物摄入量与对照组相匹配，体重也没有下降。在此，我们建议 进行(1)TRF在人体上的第一次全面试验和(2)第一次试验以确定 TRF的大小取决于食物摄入量的昼夜节律。我们建议的研究是一项三个平行手臂的对照研究 喂养试验旨在确定TRF作为一种改善心脏代谢健康的疗法的有效性 糖尿病前期成年人。N=144名糖尿病前期成人(体重指数25-50公斤/平方米；年龄18-75岁)将随机分为 三种等卡路里进食时间表之一：(1)早期TRF：从上午8点到下午2点的6小时喂食间隔；(2)中午 TRF：从下午2点到晚上8点，喂食间隔6小时；和(3)控制时间表：从上午8点到晚上8点，进食间隔12小时 在10周的时间里，参与者将在视频监控的远程监控下吃卡路里匹配的食物，以及 食物摄入量将在每餐的基础上与对照组精确匹配，以确保不会有体重下降 发生。这项研究的终点将在24小时的住院测试期内进行测量，包括基线和后 干预。主要终点是24小时血糖控制，通过24小时血糖平均值来衡量 和胰岛素；这一数据将被测量的胰岛素敏感性和分泌的机械数据补充。 在同一天进行了三次相同的饮食耐量测试。次要终点是心血管疾病 危险因素，通过24小时血压和空腹血脂水平以及炎症和氧化水平来衡量 重音标记。我们假设，两种TRF时间表都将改善心脏代谢健康，但 TRF将取决于食物摄入量的昼夜节律，改善的顺序是早期TRF和GT；中期 一天TRF和>T；对照。这项研究将为(1)TRF是否可以用于治疗新陈代谢提供关键的见解 疾病；(2)每日禁食时间的长短(间歇禁食)与 代谢健康的昼夜节律进食时间(进餐时间)；以及(3)是否不吃早餐(相当于 在晚餐时间不变的情况下，对新陈代谢健康有益或有害。

PROJECT SUMMARY Increasing evidence suggests that while poor meal timing can cause cardiometabolic disease, optimized meal timing may reverse it. Time-restricted feeding (TRF) is a novel type of intermittent fasting that involves eating within a ≤10-hour period, followed by a ≥14 hour daily fast. Studies in rodents report that TRF improves glycemic control, lowers insulin levels, reduces hepatic fat, prevents hyperlipidemia, reduces infarct volume after stroke, and improves inflammatory markers, relative to eating throughout the day. Importantly, the effects of TRF may depend on the circadian timing of food intake. Previous TRF trials in humans that limited food intake to the middle of the daytime (mid-day TRF) reported positive results, while trials that limited food intake to late in the day reported null or negative results. Building on these studies, we recently conducted the first clinical trial of TRF where food intake is limited to early during the daytime (early TRF) and found that five weeks of early TRF improved insulin sensitivity, β-cell responsiveness, blood pressure, and oxidative stress in prediabetic men— even though food intake was matched to the control arm and no weight loss occurred. Here, we propose to conduct both (1) the first full-scale trial of TRF in humans and (2) the first trial to determine whether the effects of TRF depend on the circadian timing of food intake. Our proposed study is a three-parallel-arm, controlled feeding trial designed to determine the efficacy of TRF as a therapy to improve cardiometabolic health in prediabetic adults. N=144 prediabetic adults (BMIs 25-50 kg/m2; aged 18-75 years old) will be randomized to one of three isocaloric eating schedules: (1) early TRF: 6-hour feeding interval from 8 am-2 pm; (2) mid-day TRF: 6-hour feeding interval from 2 pm-8 pm; and (3) control schedule: 12-hour eating interval from 8 am-8 pm. For 10 weeks, participants will eat calorie-matched meals under remote supervision by video monitoring, and food intake will be precisely matched on a meal-by-meal basis to the control group to ensure that no weight loss occurs. The study endpoints will be measured during a 24-hour inpatient test period at both baseline and post- intervention. The primary endpoint is 24-hour glycemic control as measured by 24-hour mean values of glucose and insulin; this data will be complemented by mechanistic data on insulin sensitivity and secretion, as measured by three identical meal tolerance tests on the same day. The secondary endpoints are cardiovascular disease risk factors, as measured by 24-hour blood pressure and fasting levels of lipids and inflammatory and oxidative stress markers. We hypothesize that both TRF schedules will improve cardiometabolic health, but the effects of TRF will depend on the circadian timing of food intake, with the order of improvements being early TRF > mid- day TRF > control. This study will provide critical insight into (1) whether TRF can be used to treat metabolic disease; (2) the relative importance of the length of the daily fasting period (intermittent fasting) versus the circadian timing of food intake (meal timing) for metabolic health; and (3) whether breakfast skipping (tantamount to mid-day TRF) is beneficial or detrimental for metabolic health when dinner time is unchanged.