Gül Turan¹, Ayesha M.F. Heinis¹, Marleen Olde Bekkink², Silvie Timmers³, Jaap Keijer¹, Marlou L. Dirks^1,4

¹Human and Animal Physiology, Wageningen University, Wageningen,

²Department of internal medicine, Hospital Gelderse Vallei, Ede,

³Department of Physiology, Radboud University Medical Center, Nijmegen,

⁴Public Health and Sport Sciences, University of Exeter, UK

gul.turan@wur.nl

Background: Type 2 diabetes (T2D) is characterised by insulin resistance and metabolic inflexibility. We investigated the effect of thrice-daily ingestion of the same meal on whole-body insulin sensitivity and substrate oxidation in individuals with normoglycaemia (CON) and T2D.

Methods: Five individuals with T2D (68±4y, BMI 26.3±1.6 kg·m^-2) and five CON (68±3y, BMI 25.1±0.7 kg·m^-2) consumed the same standardized mixed meal (30% daily energy requirements) at 9am, 2pm, and 7pm. Whole-body substrate oxidation was assessed pre- and postprandially (indirect calorimetry), and insulin sensitivity using the 3-h Matsuda index (repeated blood sampling).

Results: Fasting whole blood glucose was higher in T2D than CON (5.4±0.7 vs 3.7±0.1 mmol·L⁻¹, P<0.05) and increased similarly in both groups in response to meal ingestion (to 6.0±0.4 and 8.5±0.5 mmol·L⁻¹ in CON and T2D, respectively; interaction P>0.05).  Fasting serum insulin in T2D was numerically lower than CON (8.7±4.2 vs 9.9±3.6 µU·mL⁻¹, P>0.05). Average postprandial serum insulin concentrations were lower at lunch (39±7 µU·mL⁻¹) and dinner (44±9) than at breakfast (54±10) in both groups (interaction P>0.05). The MATSUDA index indicated higher insulin sensitivity in CON (8.1±2.0, 12.4±3.2, 9.9±2.1) than T2D (5.2±2.4, 5.4±3.7, 4.2±2.4; P<0.05) across meals. Average RER was higher at dinner than at breakfast (0.87±0.01 vs 0.85±0.01; P<0.05) in both groups, driven by higher carbohydrate oxidation (0.20±0.01 vs 0.17±0.01 g/min; P<0.05) and a tendency toward lower fat oxidation (0.06±0.01 vs 0.07±0.01 vs; P<0.10) at dinner.

Conclusion: Thrice-daily ingestion of the same meal led to higher postprandial glucose concentrations, resulting in lower whole-body insulin sensitivity across the entire day in individuals with T2D. Consuming the same meal at dinnertime resulted in higher postprandial carbohydrate oxidation than when the same meal was consumed at breakfast. However, the metabolic response to repeated meal ingestion was comparable between groups, indicating that T2D did not affect the repeated-meal effect.