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

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, HbA1c 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 HbA1c 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 HbA1c (-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).

Intestinal Glucose Absorption Is a Key Determinant of 1-Hour Postload Plasma Glucose Levels in Nondiabetic Subjects.

CONTEXT: One-hour postload hyperglycemia, defined as 1-hour plasma glucose (1hPG) ≥ 155 mg/dL during an oral glucose tolerance test (OGTT), has been proposed as an independent predictor of type 2 diabetes. Recent evidence suggests that 1-hour hyperglycemia can be explained by enhanced duodenal glucose absorption, which in turn may increase the rate of appearance of oral glucose in the systemic circulation (RaO). However, the impact of RaO on 1hPG and 1-hour glucose excursions (incremental area under the curve calculated through the first hour after glucose ingestion; glucose iAUC1h) is still unknown. OBJECTIVE: We quantified the relative contribution of postload RaO to 1hPG and glucose iAUC1h with respect to other major glucose homeostatic mechanisms in nondiabetic participants. PARTICIPANTS AND METHODS: Model-derived ß-cell function, insulin clearance, glucose metabolic fluxes, and peripheral and hepatic insulin sensitivity were measured during a 75-g OGTT by a double tracer method in 23 nondiabetic volunteers. RESULTS: Early insulin secretion, whole-body insulin sensitivity, and plasma glucose disposal were significantly impaired in participants with 1hPG ≥ 155 mg/dL (n = 11), who also showed nominally greater RaO (19%; P = 0.10). In multivariable models, postload RaO showed an independent effect on both 1hPG and glucose iAUC1h (partial r2 = 0.26 and 0.48, respectively; P < 0.003). The relative contribution of RaO to 1hPG (23%) and glucose iAUC1h (30%) was similar to that of early insulin secretion and peripheral insulin sensitivity and greater than that of hepatic insulin sensitivity. CONCLUSIONS: Our data highlight the primary role of RaO as a major determinant of 1-hour postprandial glucose excursions in nondiabetic participants.