Early time-restricted carbohydrate consumption vs conventional dieting in type 2 diabetes: a randomised controlled trial

Abstract

Aims/hypothesis: Early time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions.

Methods: In this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.2±7.9 years, 47.8% women, BMI 29.4±3.7 kg/m², HbA_1c 49±5 mmol/mol [6.6±0.5%]) were randomised, using computer-generated random numbers, to a 12 week eTRC diet or a Mediterranean-style control diet with matched energy restriction and macronutrient distribution (50% carbohydrate, 30% fat and 20% protein). The primary outcome was the between-group difference in HbA_1c at 12 weeks. Body composition, 14 day flash glucose monitoring and food diary analysis were performed every 4 weeks. Mixed meal tolerance tests with mathematical beta cell function modelling were performed at baseline and after 12 weeks.

Results: Twelve (85.7%) participants in the eTRC arm and 11 (84.6%) participants in the control arm completed the study, achieving similar reductions in body weight and fat mass. The two groups experienced comparable improvements in HbA_1c (-3 [-6, -0.3] mmol/mol vs -4 [-6, -2] mmol/mol, corresponding to -0.2 [-0.5, 0]% and -0.3 [-0.5, -0.1]%, respectively, p=0.386), fasting plasma glucose, flash glucose monitoring-derived glucose variability and mixed meal tolerance test-derived glucose tolerance, insulin resistance, insulin clearance and plasma glucagon levels, without changes in model-derived beta cell function parameters, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and non-esterified fatty acid levels. The two diets similarly reduced liver function markers and triglyceride levels, being neutral on other cardiometabolic and safety variables. In exploratory analyses, diet-induced changes in body weight and glucometabolic variables were not related to the timing of carbohydrate intake.

Conclusions/interpretation: The proposed eTRC diet provides a feasible and effective alternative option for glucose and body weight management in individuals with type 2 diabetes, with no additional metabolic benefits compared with conventional dieting.

Trial registration: ClinicalTrials.gov NCT05713058 FUNDING: This study was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Italian Society of Diabetology (SID).

Keywords: Blood glucose control; Circadian rhythm; Dietary carbohydrates; Glucagon; Glucose-dependent insulinotropic peptide; Nutrition therapy; Obesity; Randomised controlled trial; Time-restricted eating; Type 2 diabetes.

Fig. 1

Changes in body weight (a), BMI (b), fat mass (c), fatty liver index (d), waist circumference (e) and visceral fat (f) in individuals with type 2 diabetes randomly assigned to a 12 week eTRC diet (red circles) or a Med diet (blue triangles) with matched energy restriction and macronutrient distribution. Data are mean ± SEM. Group differences were tested by two-way ANOVA for repeated measures including diet (D), group (G) and diet × group (D×G) interaction as factors

Fig. 2

Changes in HbA_1c (a), fasting glucose (b) and insulin (c) in individuals with type 2 diabetes randomly assigned to a 12 week eTRC diet (red circles) or a Med diet (blue triangles) with matched energy restriction and macronutrient distribution. Data are mean ± SEM. Group differences were tested by two-way ANOVA for repeated measures including diet (D), group (G) and diet × group (D×G) interaction as factors. Representative 14 day flash glucose monitoring reports of participants from the eTRC diet (d) and Med diet (e) groups. Median (continuous line) and 10th and 90th percentiles (shaded area) are shown. Flash glucose monitoring-derived average interstitial glucose (f), glucose CV (g) and percentage of time spent within the target glucose range of 3.9 to 10 mmol/l (h), above the target glucose range (i) or with interstitial glucose levels above 7.8 mmol/l (j) or 6.7 mmol/l (k) in free-living conditions. Group differences were tested by Mann–Whitney U test

Fig. 3

Changes in plasma glucose (a), insulin (b), C-peptide (c), ISR (d), model-derived beta cell glucose sensitivity (β-GS) (e), ISR@5.5 (f), beta cell rate sensitivity (β-RS) (g), potentiation factor ratio (h), fasting insulin clearance (i), total insulin clearance (j), HOMA-IR (k), Matsuda index (l), NEFA (m), GLP-1 (n), GIP (o) and glucagon (p) measured during a 180 min MMTT in individuals with type 2 diabetes randomly assigned to a 12 week eTRC diet (red circles) or a Med control diet (blue triangles) with matched energy restriction and macronutrient distribution. Data are mean ± SEM. Dashed lines in panels (a–d) and (m–p) indicate baseline values at week 0. Group differences were tested by two-way ANOVA for repeated measures including diet (D), group (G) and diet × group (D×G) interaction as factors. Ins, insulin