Effect of Time-restricted Eating on Behaviour and Metabolism in Overweight Individuals at High Risk of Type 2 Diabetes - the RESET Study

Brief Summary

Detailed Description

Overweight and obese individuals with pre-diabetes or with a family history of diabetes or cardiovascular disease (CVD) are at high risk for developing type 2 diabetes (T2D) and CVD. Current prevention and treatment of obesity and T2D include energy restricted diets and increased levels of physical activity; however, adequate adherence to such strategies is difficult, and maintenance is challenging for most individuals, which stresses the need for feasible and sustainable interventions. Circadian rhythms of behaviour and metabolism are closely related to the daily light/dark cycle and sleep-wake patterns and timing of food intake and fasting periods may affect the circadian rhythms of metabolic organs. In an evolutionary perspective, the pattern of food consumption has been characterised by periods of caloric intake when food was available and subsequent periods of fasting 9. This cyclic pattern leads to cycles of absorption and storage of energy and utilisation of the energy for e.g. tissue repair, stress resistance and vitality where expression of metabolic regulators coordinates with cellular processes, leading to efficient metabolism 10. Factors including the 24-hour availability of energy-dense foods, busy time schedules, different eating and sleep patterns during weekdays and weekends (i.e. 'social jetlag') challenge the feeding-fasting paradigm. Recent data suggest that an erratic diurnal eating pattern characterised by food intake largely spread throughout hours awake (≥15 h) and a concomitant short fasting period is highly prevalent in humans and animal suggest that circadian misalignment of food intake is associated with adverse metabolic effects. A number of animal studies and a few small studies in humans have reported promising effects of time-restricted eating (TRE), without concomitant dietary restrictions, on body weight and other cardiometabolic risk factors. There is a lack of randomized controlled trials investigating effect of TRE in individuals at high risk of type 2 diabetes and cardiovascular diseases. The aim of the present study is to investigate effects of 12 weeks TRE on behaviour and metabolism in individuals with overweight or obesity at high risk of type 2 diabetes. Maintenance will be assessed at a follow-up visit 13 weeks after completion of the trial (26 weeks). Testing will be conducted at baseline and after 6, 12, and 26 weeks. Participants are instructed to follow randomization during one week assessment periods after testing at 6 and 12 weeks. Therefore, the total duration of the intervention is 13 weeks.

Primary Outcomes

Secondary Outcomes

• Circulating proteins that associate with low-grade inflammation and lipid metabolism(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Implicit wanting(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Explicit liking(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Diastolic blood pressure (mmHg)(Changes from baseline. Measured at all four visits (Baseline and after 6, 12, and 26 weeks))
• Hormones(Changes from baseline. Measured in the blood in the fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test (4 hours) at baseline and end of the intervention (after 12 weeks))
• Insulin sensitivity (indices)(At all four visits (Baseline and after 6, 12, and 26 weeks))
• Continuous overall net glycaemic action (CONGA)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Standard deviation of glucose concentrations(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Physical activity (time spent at different intensities)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Macronutrient intake (energy percentage)(Changes from baseline. Registered 3 days after the test days at baseline and after 6 and 12 weeks)
• Hip circumference (cm)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Fat free mass (kg)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Fat percentage (%)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Heart rate response to forced exhalation during rest (valsalva maneuver)(Changes from baseline. Measured at visits at baseline and end of the intervention (after 12 weeks))
• Small bowel transit time (hours and minutes)(Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).)
• Large bowel transit time (hours and minutes)(Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).)
• Motility index(Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).)
• Emotions measured using facial expression analyses(Changes from baseline. Fasted state at all four visits (baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Explicit wanting(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Insulin resistance (indices)(At all four visits (Baseline and after 6, 12, and 26 weeks))
• Mean glucose concentrations(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Body weight (kg)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Body mass index (kg/m^2)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Fat mass (kg)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Waist circumference (cm)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks))
• Systolic blood pressure (mmHg)(Changes from baseline. Measured at all four visits (Baseline and after 6, 12, and 26 weeks))
• Substrate oxidation (respiratory exchange ratio)(Changes from baseline. Measured at visits at baseline and after 12 weeks)
• Respiratory and glycolytic capacities of isolated peripheral blood mononuclear cells (PBMCs)(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Heart rate response to standing up from the supine position(Changes from baseline. Measured at visits at baseline and end of the intervention (after 12 weeks))
• Heart rate response to inhalation and exhalation(Changes from baseline. Measured at visits at baseline and end of the intervention (after 12 weeks))
• Total gastrointestinal transit time (hours and minutes)(Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).)
• HbA1c (mmol/mol and %)(Changes from baseline. All four visits (Baseline and after 6, 12, and 26 weeks))
• Heart rate (bpm)(Changes from baseline. Measured at all four visits (Baseline and after 6, 12, and 26 weeks))
• Resting energy expenditure (kcal/day)(Changes from baseline. Measured at visits at baseline and after 12 weeks)
• Metabolites(Changes from baseline. Measured in the blood in the fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test (4 hours) at baseline and end of the intervention (after 12 weeks))
• Gastric emptying time (hours and minutes)(Changes from baseline. Time after consumption of the standard mixed meal at baseline and end of the intervention (after 12 weeks).)
• Attention measured using eye tracking(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Arousal measured using galvanic skin response(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Subjective appetite(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Mean amplitude of glycaemic excursions (MAGE)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Self-reported sleepiness(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Food choice(Changes from baseline. Fasted state at all four visits (Baseline and after 6, 12, and 26 weeks) and during a mixed meal test at baseline and end of the intervention (after 12 weeks))
• Daily time spent above different glucose concentrations (e.g. >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Variation coefficients of glucose concentrations(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Timing of physical activity (hh:mm)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Energy intake (kcal/day)(Changes from baseline. Registered 3 days after the test days at baseline and after 6 and 12 weeks)
• Sleep timing (hh:mm)(Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks)
• Sleep efficiency (%)(Changes from baseline. Measured for 7 days after the test days at baseline and after 6 and 12 weeks)
• Satisfaction with the intervention (qualitative methods)(Visits at baseline and after 12 and 26 weeks. Potential drop-outs will be interviewed at the specific time point.)
• Physical activity (counts/min)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Physical activity (MET hours)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Timing of dietary intake (hh:mm)(Changes from baseline. Registered 3 days after the test days at baseline and after 6 and 12 weeks)
• Wakefulness (min)(Changes from baseline. Measured for 7 days after the test days at baseline and after 6 and 12 weeks)
• Self-reported physical activity(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported eating behavior(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Daily eating/drinking window (hh:min)(Registrered every day (13 weeks intervention and 13 weeks follow-up period))
• Physical activity energy expenditure (kcal/day)(Changes from baseline. Measured 7 days after the test days at baseline and after 6 and 12 weeks)
• Self-reported gastrointestinal symptoms (part 1)(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported gastrointestinal symptoms (part 3)(Changes from baseline. Registered 7 days after the test days at baseline and after 12 weeks)
• Feasibility of the intervention (qualitative methods)(Visits at baseline and after 12 and 26 weeks. Potential drop-outs will be interviewed at the specific time point.)
• Sleep variability (min)(Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks)
• Sleep onset latency (min)(Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks)
• Self-reported control over eating(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported sleep quality(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported chronotype(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Motivation for participation (qualitative methods)(Visits at baseline and after 12 and 26 weeks. Potential drop-outs will be interviewed at the specific time point.)
• Sleep duration (min)(Changes from baseline. Registered and measured for 7 days after the test days at baseline and after 6 and 12 weeks)
• Self-reported gastrointestinal symptoms (part 2)(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported autonomic symptoms(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported overall health and wellbeing(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Self-reported night eating(Changes from baseline. Assessed at all four visits (Baseline and after 6, 12, and 26 weeks))
• Microbiome content and diversity(Changes from baseline. Collected before or during test days at visits at baseline and after 12 weeks)