Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial.

BACKGROUND: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. METHODS: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). FINDINGS: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. INTERPRETATION: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. FUNDING: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

Human Gastrointestinal Transit and Hormonal Response to Different Meal Types: A Randomized Crossover Study.

BACKGROUND: The wireless motility capsule (WMC) technique is a noninvasive and radiation-free method for measuring regional and whole gut transit in response to ingestion of a granola bar (SmartBar) or an eggbeater meal. The WMC has the potential to measure gastrointestinal transit in metabolic research as part of a standardized mixed meal tolerance test. OBJECTIVES: To evaluate gastrointestinal transit with the WMC and postprandial plasma/serum concentrations of metabolites and gastrointestinal hormones as well as subjective appetite following ingestion of a SmartBar compared with a standardized mixed meal. METHODS: Fourteen healthy participants [3 men, median (IQR) age 53.8 (45.8; 64.50) y, body weight 63.9 (59.9; 69.7) kg, BMI 23.1 (21.8; 23.9) kg/m2] completed a 2-d crossover study. Following ingestion of either a SmartBar (260 kcal, 7 energy percent (E%) fat, 74E% carbohydrate, and 19E% protein) or a standardized mixed meal (498 kcal, 34E% fat, 49E% carbohydrate, and 17E% protein), participants swallowed the WMC. Blood samples were drawn in the fasted state and postprandially for analyses of gastrointestinal hormones and metabolites. The primary outcome was difference in gastric emptying time between the 2 test days. Wilcoxon signed rank tests were used to test differences between test days. RESULTS: Median (IQR) gastric emptying time was 98.0 (70.0; 113.0) min longer (P = 0.001) and incremental area under the curve of triglyceride, glucose-dependent insulinotropic polypeptide, and peptide YY were 40 mmol/L × min, 45.7%, and 63.7% greater after the standardized mixed meal compared with the SmartBar (all P < 0.001). CONCLUSIONS: The WMC can be used in combination with a standardized mixed meal for evaluation of gastrointestinal transit in healthy men and women. Gastric emptying time was prolonged in response to the standardized mixed meal whereas transit times of the small bowel, colon, and whole gut did not differ between the test meals.

Associations between Postprandial Gut Hormones and Markers of Bone Remodeling.

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types-a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.