Effect of medium-chain triglycerides and whey protein isolate preloads on glycaemia in type 2 diabetes: a randomized crossover study

Small nutritional preloads can reduce postprandial glucose excursions in individuals with and without metabolic syndrome or type 2 diabetes (T2D). However, most studies have focused on preloads administered before single meals and have predominantly used protein-based preloads. To investigate the effects of sequential consumption of medium-chain triglycerides (MCT) and whey protein isolate (WPI) preloads before breakfast, lunch, and dinner on postprandial, diurnal, and 24-h glycaemia in individuals with T2D. Participants with T2D were studied over 3 randomized 24-h periods. They consumed either water before standardized breakfast, lunch, and dinner (CONTROL), 15 g MCT before breakfast and water before lunch and dinner (MCT), or 15 g MCT before breakfast and 10 g WPI before lunch and dinner (MCT + WPI). Diurnal (08:00–23:00 h) and 24 h (08:00–08:00 h) glycaemia (incremental AUC [Iauc]) and glycemic variability (%coefficient of variation [%CV]) were evaluated by continuous glucose monitoring. Postprandial glycaemia (PPG) after breakfast and lunch was assessed by arterialized blood glucose iAUC. In 21 enrolled patients (8 males/13 females, mean ± standard deviation age 55.1 ± 8.5 y, body mass index 31.7 ± 4.3 kg·m−2, glycated hemoglobin 59 ± 12 mmol·mol−1) diurnal and 24-h iAUC were similar across interventions, whereas 24-h %CV was lower in MCT (16.8 ± 0.8%, P = 0.033) and MCT + WPI (16.1 ± 0.9%, P = 0.0004) than CONTROL (18.7 ± 0.9%). PPG iAUC was ∼17% lower after breakfast in MCT and MCT + WPI compared with CONTROL, but only the MCT + WPI lowered glucose by 20% (P = 0.002) over the entire day (08:30–17:30 h). Gastric inhibitory polypeptide (GIP) (P = 0.00004), peptide YY (PYY) (P = 0.01), and β-hydroxybutyrate (P = 0.0001) were higher in MCT and MCT + WPI than CONTROL. Subjective appetite ratings were lower after breakfast and lunch in MCT + WPI (P = 0.001). Sequential consumption of MCT and WPI preloads did not affect diurnal or 24-h glycaemia but lowered PPG and 24-h glycemic variability in individuals with T2D. These effects were associated with increased circulating β-hydroxybutyrate, PYY, and GIP, and suppression of appetite. This trial was registered at clinicaltrials.gov as NCT04905589 (https://clinicaltrials.gov/study/NCT04905589).