Comparing the effectiveness of calorie restriction with and without time-restricted eating on the circadian regulation of metabolism – rationale and protocol of a three-arm randomised controlled trial in adults at risk of type 2 diabetes

Background: Time-restricted eating (TRE) may extend the cardiometabolic health benefits of calorie restriction (CR). However, few studies have compared its effect on the circadian regulation of metabolic processes, including glucose metabolism. The optimal time of day to initiate TRE also remains unclear. Aim and hypothesis: To compare CR alone or in combination with TRE, initiated at either 0800 or 1200, on postprandial metabolism. We hypothesise that relative to CR, early CR (eCR) and delayed CR (dCR) will improve glucose tolerance in response to three identical meals consumed over the day. Methods: A parallel, single-blinded, three-arm randomised controlled trial will be conducted in 114 adults, aged 35 to 75 years with a BMI ≥ 25.1 but < 45.0 kg/m ² , elevated waist circumference and fasting blood glucose (≥ 5.6 mmol/L), and who score ≥12 on the Australian Type 2 Diabetes Risk Assessment tool. Participants will be stratified by sex and fasting blood glucose (≤ 6.0 mmol/L; > 6.0 mmol/L) and then randomised (1:1:1) to CR (unrestricted meal timing), eCR (0800 to 1600) or dCR (1200 to 2000) for 8 weeks. Participants will attend the research centre for a 26-h stay at baseline and week 8. A follow-up visit for assessment of fasting body weight and a blood sample will be collected 16 weeks after primary endpoint completion. Analysis will be performed using linear mixed models adjusted for baseline and stratification factors. Outcomes: The primary outcome is the change in postprandial glucose area under the curve (AUC) in response to three identical mixed meals served according to study protocol at week 8. Secondary outcomes are changes in postprandial insulin AUC, fasting insulin, fasting glucose, and glycated haemoglobin. Conclusions: This randomised clinical trial will be the first to delineate the benefits of CR alone or in combination with time restricted eating on postprandial glucose metabolism over the day in adults at increased risk of type 2 diabetes. Trial registration: NCT05769335; March 15, 2023