Meal-sequence and postprandial glucose excursions: A time course study to find optimal interval in healthy Japanese 

Background: Postprandial glucose concentration is influenced by a number of factors including meal size and composition, gastric emptying and intestinal glucose absorption through the secretion and action of insulin, glucagon and incretins. Recent research shows that preloading foods rich in protein or fat before carbohydrate intake can attenuate postprandial glucose elevation. This study expands upon a previous study, which investigated the effects of eating fish or meat 15 minutes before rice, and found that eating fish or meat 15 minutes before rice enhanced GLP-1 secretion and improved postprandial glucose excursions in Japanese patients with type 2 diabetes. Thus, the effects of meal-sequence including eating combination meal or various interval times on postprandial glucose excursion in healthy people are not well understood. 
Aim: In this study, we sought to clarify the optimal time interval between eating other foods and rice using combination meal for ameliorating postprandial glucose excursion.
Materials and Methods:
Participants: This is a single centre randomized controlled trial that involved fifteen healthy volunteers (n=15, age 31.0±4.5 years, HbA1c 5.9±0.2%). All participants did not have diabetes, gastrointestinal tract disease including gastroparesis, history of gastrointestinal operation, cardiac disease, pulmonary disease, pancreatic disease, liver disease, renal disease, alcohol or drug abuse, glucose-lowering medication, diabetogenic medication or malignancy, or pregnancy as well as thyroid diseases. 
Meal-sequence test: Meal sequence tests were performed at lunchtime at least after 5 hours fast. Meal sequences consisted of eating other foods of a combination hospital meal 15 minutes before rice (-15 min), 10 minutes before rice (-10 min), 5 minutes before rice (-5 min), with rice (0 min), or 15 minutes after rice (+15 min) on 5 separate days for each of the participants. The total energy of the test meal was 550±36 kcal, 16.5% from protein, 23.5% from fat and 60% from carbohydrate 60%.
Monitoring: Interstitial fluid glucose levels were monitored every 15 min by continuous glucose monitoring (flush CGM; Abbott® Real time monitoring).
Statistical analysis: Results are reported as mean ± SEM. Data analysis was performed with t- test and ANOVA. P value <0.05 was taken to indicate significant differences.
Result: Preloading of other foods of a meal before rice (-15 min, -10 min, and -5 min) result in significant improvement in postprandial glucose excursions compared to consuming both components at the same time (0 min) or consuming rice before other foods (15 min). We also conclude that there was no significant difference between preloading at -5, -10 or -15 minutes before rice.
Discussion and conclusion: We confirm in this study that preloading other foods of a meal before consuming rice results in more favourable post prandial glucose excursions. We also conclude that this meal-sequence shows beneficial effects as early as 5 min after other foods consumption. The current findings solidify importance and effectiveness of meal-sequence in medical nutritional therapy to control postprandial glucose elevation; and might be applicable to individuals with type 2 diabetes.