Impact of the morning vs. evening consumption of high-protein meals on the metabolic state of individuals with prediabetes or type 2 diabetes: pilot results of the PROTIME trial

Aims: High-protein diets have been shown to positively impact glucose metabolism, but the role of timing of the protein intake is unknown. Building on this, we conduct a clinical trial comparing two isocaloric and normoproteic diets with different distribution of protein intake throughout the day in individuals with prediabetes and non-insulin-treated type 2 diabetes (T2D). Specifically, this study aims (i) to investigate the feasibility of the interventions and (ii) to determine preliminary efficacy of tested diets for improving glucose metabolism and other cardiometabolic parameters.

Methods: For the ongoing PROTIME trial (NCT06382480), 30 overweight or obese individuals (BMI>25 kg/m2) with prediabetes and non-insulin-treated T2D are being recruited, aiming for an equal distribution between those with prediabetes and those with T2D. The trial employs a cross-over design to compare two isocaloric 4-week dietary interventions: a high-protein (HP) breakfast and high-carbohydrate (HC) dinner (HP/HC intervention) versus a HC breakfast and HP dinner (HC/HP intervention), separated by a 4-week wash-out period. A high-carb meal contains approximately 60 EN% carbohydrates, 30 EN% fat and 10 EN% protein, whereas a high-protein meal contains 35 EN% carbohydrates, 30 EN% fat and 35 EN% protein. Participants received personalized nutritional plans, reported food intake and underwent continuous glucose monitoring (CGM) using FreeStyle Libre Pro iQ sensors as well as activity monitoring using Actigraph wGT3X-BT Accelerometer. Glucose metrics and glycemic variability indices are being analyzed using EasyGV© software.

Results: These preliminary results show high adherence to both interventions. In the HP/HC intervention, the composition of reported morning meals was 35.9±4.5 EN% carbohydrates, 31.0±3.1 EN% fat and 34.4±2.7 EN% protein and evening meals included 55.8±6.7 EN% carbohydrates, 29.6±5.1 EN% fat and 10.9±2.1 EN% protein (n=4). In the HC/HP intervention, the composition of morning meals was 60.3±3.2 EN% carbohydrates, 29.2±3.2 EN% fat and 10.8±0.6 EN% protein and evening meals included 34.5±5.6 EN% carbohydrates, 33.3±7.1 EN% fat and 32.9±5.7 EN% protein (n=5). Changes in CGM were only found for the mean absolute glucose (MAG) in HC/HP indicating increased fluctuations in blood glucose levels (p=0.02). No significant changes were observed in blood lipids, with the exception of high-density lipoprotein (HDL), which decreased upon HC/HP (p=0.01). Satiety and hunger scores did not differ in both interventions. HbA1c showed a tendency toward improvement with HC/HP (p=0.07).

Conclusion: The preliminary findings of the PROTIME trial have shown a high feasibility of both dietary interventions. Cardiometabolic effects of protein distribution need to be investigated in the larger cohort.

Publication History

Article published online:
28 May 2025