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

限时喂养对成人糖尿病前期患者 24 小时血糖控制、血压和心血管疾病危险因素的影响

• 批准号: 10651596
• 负责人: Courtney Marie Peterson
• 金额: $ 64.78万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10651596
• 关键词: Adult; Beta Cell; Blood Glucose; Blood Pressure; Body Weight decreased; Calories; Cardiometabolic Disease; Cellular Metabolic Process; Cholesterol; Circadian Rhythms; Clinical Trials; Complement; Control Groups; Data; Dyslipidemias; Eating; Fasting; Fatty acid glycerol esters; Food; Glucose; Health; Hepatic; High Density Lipoproteins; High Fat Diet; Hour; Human; Hydrocortisone; Hyperglycemia; Hyperlipidemia; Infarction; Inflammation; Inflammatory; Inpatients; Insulin; Insulin Resistance; Interleukin-1 beta; Interleukin-10; Interleukin-4; Interleukin-6; Intermittent fasting; Isoprostanes; Length; Lipids; Low-Density Lipoproteins; Macronutrients Nutrition; Measures; Metabolic; Metabolic Diseases; Modeling; Monitor; Mus; Obesity; Oral; Oxidative Stress; Participant; Persons; Prediabetes syndrome; Publishing; Randomized; Reporting; Risk Factors; Rodent; Schedule; Supervision; System; TNF gene; Testing; Time; Time-restricted feeding; Triglycerides; aged; arm; cardiometabolism; cardiovascular disorder risk; circadian; efficacy evaluation; fasting glucose; feeding; feeding schedule; glucose metabolism; glycemic control; improved; inflammatory marker; insight; insulin secretion; insulin sensitivity; lipid metabolism; men; novel; post intervention; post stroke; prevent; primary endpoint; secondary endpoint; time interval; trial design

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.

项目摘要 越来越多的证据表明，虽然不良的进餐时间可能会导致心脏代谢疾病，但优化的膳食 时间限制喂养（TRF）是一种新型的间歇性禁食， ≤10小时内，随后每日空腹≥14小时。啮齿动物研究报告TRF改善血糖 控制，降低胰岛素水平，减少肝脏脂肪，预防高脂血症，减少中风后梗死体积， 并改善炎症标志物，相对于整天进食。重要的是，TRF的影响可能 取决于食物摄入的昼夜节律。以前的TRF在人类中的试验将食物摄入量限制在中间 白天（中午TRF）的试验报告了阳性结果，而将食物摄入限制在当天晚些时候的试验报告了阳性结果。 报告无效或阴性结果。在这些研究的基础上，我们最近进行了TRF的首次临床试验 其中食物摄入仅限于白天早期（早期TRF），并发现五周的早期TRF 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且没有发生体重减轻。在此，我们建议 进行（1）TRF在人类中的第一次全面试验和（2）第一次试验，以确定其效果是否 的TRF取决于食物摄入的昼夜节律。我们提出的研究是一个三平行臂，控制 喂养试验，旨在确定TRF作为治疗改善心脏代谢健康的有效性， 糖尿病前期成人N=144例糖尿病前期成人（BMI 25-50 kg/m2;年龄18-75岁）将被随机分配至 三种等热量进食时间表之一：（1）早期TRF：从上午8点到下午2点的6小时进食间隔;（2）中午 TRF：从下午2点到晚上8点的6小时喂食间隔;和（3）控制时间表：从上午8点到晚上8点的12小时进食间隔。 在10周的时间里，参与者将在视频监控的远程监督下吃热量匹配的饭菜， 每餐的食物摄入量将与对照组精确匹配，以确保体重不会减轻。 发生。研究终点将在基线和治疗后的24小时住院试验期间进行测量。 干预主要终点是24小时血糖控制，通过24小时血糖平均值测量 和胰岛素;该数据将由胰岛素敏感性和分泌的机制数据补充，如测量的 在同一天进行三次相同的膳食耐受性测试。次要终点是心血管疾病 风险因素，通过24小时血压和空腹血脂水平以及炎症和氧化水平测量 压力标记。我们假设两种TRF方案都能改善心脏代谢健康，但 TRF将取决于食物摄入的昼夜时间，改善的顺序是早期TRF >中期TRF。 天TRF >对照。这项研究将提供关键的见解（1）TRF是否可以用于治疗代谢性疾病， 疾病;（2）每日禁食期（间歇性禁食）的长度与 食物摄入的昼夜节律时间（进餐时间）对代谢健康的影响;以及（3）是否不吃早餐（相当于 当晚餐时间不变时，至中午TRF）对代谢健康有益或有害。