The effects of fasting compared to eating a meal or snack during simulated night shift on changes in metabolism associated with circadian misalignment: a protocol and methods paper.

Study Objectives: This protocol paper outlines the methods that will be used to examine the impact of altering meal timing on metabolism, cognitive performance, and mood during the simulated night shift. Methods: Participants (male and female) will be recruited according to an a priori selected sample size to complete a 7-day within and between participant's laboratory protocol. Participants will be randomly assigned to one of the three conditions: meal at night or snack at night or no meal at night. This protocol includes an 8-hour nighttime baseline sleep, followed by 4 consecutive nights of simulated nightshift (7 hours day sleep; 10:00-17:00 hours), and an 8-hour nighttime sleep (return to dayshift). During the simulated night shift, meals will be provided at ~06:30, 09:30, 14:10, and 19:00 hours (no eating at night); ~06:30, 19:00, and 00:30 hours (meal at night); or ~06:30, 14:10, 19:00, and 00:30 hours (snack at night). Meal composition will be strictly controlled throughout the study (45%-65% carbohydrates, 15%-25% protein, and 20%-35% fat per day) with daily energy provided to meet individual needs using the Harris-Benedict equation (light/sedentary activity). The primary outcome measures are serum concentrations of blood glucose, insulin, and free fatty acids area under the curve in response to the oral glucose tolerance test. Mixed-effect ANOVAs will be conducted. Conclusions: This protocol paper describes a methodology to describe an innovative approach to reduce the metabolic disease impact associated with shift work.

Study protocol for the Shifting Weight using Intermittent Fasting in night shift workers (SWIFt) study: a three-arm randomised controlled trial comparing three weight loss strategies in night shift workers with obesity.

INTRODUCTION: Shift workers are at an increased risk of developing obesity and type 2 diabetes. Eating and sleeping out of synchronisation with endogenous circadian rhythms causes weight gain, hyperglycaemia and insulin resistance. Interventions that promote weight loss and reduce the metabolic consequences of eating at night are needed for night shift workers. The aim of this study is to examine the effects of three weight loss strategies on weight loss and insulin resistance (HOMA-IR) in night shift workers. METHODS AND ANALYSIS: A multisite 18-month, three-arm randomised controlled trial comparing three weight loss strategies; continuous energy restriction; and two intermittent fasting strategies whereby participants will fast for 2 days per week (5:2); either during the day (5:2D) or during the night shift (5:2N). Participants will be randomised to a weight loss strategy for 24 weeks (weight loss phase) and followed up 12 months later (maintenance phase). The primary outcomes are weight loss and a change in HOMA-IR. Secondary outcomes include changes in glucose, insulin, blood lipids, body composition, waist circumference, physical activity and quality of life. Assessments will be conducted at baseline, 24 weeks (primary endpoint) and 18 months (12-month follow-up). The intervention will be delivered by research dietitians via a combination of face-to-face and telehealth consultations. Mixed-effect models will be used to identify changes in dependent outcomes (weight and HOMA-IR) with predictor variables of outcomes of group, time and group-time interaction, following an intention-to-treat approach. ETHICS AND DISSEMINATION: The study protocol was approved by Monash Health Human Research Ethics Committee (RES 19-0000-462A) and registered with Monash University Human Research Ethics Committee. Ethical approval has also been obtained from the University of South Australia (HREC ID: 202379) and Ambulance Victoria Research Committee (R19-037). Results from this trial will be disseminated via conference presentations, peer-reviewed journals and student theses. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN-12619001035112).

Time-restricted eating improves glycemic control and dampens energy-consuming pathways in human adipose tissue.

OBJECTIVE: We sought to examine the effects of 8 wk of time-restricted eating (TRE) on glucose metabolism and the adipose tissue transcriptome during a metabolic ward stay in men with obesity. METHODS: In a single-arm, pre-post trial, 15 men (ages 63 ± 4 y, body mass index = 30.5 ± 2.4 kg/m2, waist circumference = 113 ± 4 cm) with obesity but no history of diabetes were enrolled and underwent 2 wk of baseline monitoring before they were instructed to eat their regular diets within a contiguous 10-h time frame each day for 8 wk. Metabolic testing was performed at baseline and week 8 during a 35-h metabolic ward stay, during which all food intake was strictly timed and controlled. Identical meal-tolerance tests were performed at breakfast and dinner. Blood glucose, glucoregulatory hormones, and subjective appetite score were measured. Subcutaneous adipose tissue biopsies were performed and the transcriptome was assessed. RESULTS: The primary outcome, plasma glucose area under the curve, was altered by TRE, being unchanged at breakfast but increased at dinner. However, TRE reduced fasting glucose, glycated hemoglobin, body weight, and body fat, and increased glucose-dependent insulinotropic peptide area under the curve at dinner. In subcutaneous adipose tissue, 117 genes were up-regulated and 202 genes down-regulated by TRE. Pathway analysis revealed down-regulation of genes involved in proteasome function and mitochondrial regulation. CONCLUSIONS: TRE had a net effect of reducing glycemia and dampening energy-consuming pathways in adipose tissue.