Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial

Aims/hypothesis Investigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated. Methods The experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n= 10), with age 30-75 years, HbA(1c) 9.0% (75 mmol/mol) or less, and BMI 35 kg/m(2) or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by C-13-acetate breath test involving measurement of (CO2)-C-13 in breath samples collected before and after ingestion of rice steamed with C-13-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment. Results FR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC-15-240 min-glucose: type 2 diabetes, FR 2,326.6 +/- 114.7 mmol/l x min, MR 2, 257.0 +/- 82.3 mmol/l x min, RF 2,475.6 +/- 87.2 mmol/l xmin [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 +/- 72.3 mmol /l x min, MR 1, 389. 7 +/- 69.4 mmol/l x min, RF 1,483.9 +/- 72.8 mmol/l xmin) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, FR 1.94 +/- 0.22 mmol/l, MR 1.68 +/- 0.18 mmol/l, RF 2.77 +/- 0.24 mmol/l [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 0.95 +/- 0.21 mmol/l, MR 0.83 +/- 0.16 mmol/l, RF 1.18 +/- 0.27 mmol/l). FR and MR also enhanced GLP-1 secretion, MR more strongly than FR or RF (AUC-15-240 min-GLP-1: type 2 diabetes, FR 7,123.4 +/- 376.3 pmol/l xmin, MR 7,743.6 +/- 801.4 pmol/l xmin, RF 6,189.9 +/- 581.3 pmol/l xmin [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 +/- 324.6 pmol/l xmin, MR 4,897.7 +/- 330.7 pmol/l xmin, RF 3,747.5 +/- 572.6 pmol/l xmin [p < 0.05 for MR vs RF and MR vs FR]). FR and MR delayed gastric emptying (Time50%: type 2 diabetes, FR 83.2 +/- 7.2 min, MR 82.3 +/- 6.4 min, RF 29.8 +/- 3.9 min [p< 0.05 for FR vs RF and MR vs RF]; healthy, FR 66.3 +/- 5.5 min, MR 74.4 +/- 7.6 min, RF 32.4 +/- 4.5 min [p < 0.05 for FR vs RF and MR vs RF]), which is associated with amelioration of postprandial glucose excursion (AUC-15-120 min-glucose: type 2 diabetes, r = -0.746, p < 0.05; healthy, r = -0.433, p < 0.05) and glucose variability (SD-15240 min-glucose: type 2 diabetes, r = -0.578, p < 0.05; healthy, r = -0.526, p < 0.05), as well as with increasing GLP-1 (AUC-15-120 min-GLP-1: type 2 diabetes, r = 0.437, p< 0.05; healthy, r = 0.300, p = 0.107) and glucagon (AUC-15-120 min-glucagon: type 2 diabetes, r = 0.399, p < 0.05; healthy, r = 0.471, p < 0.05). The measured outcomes were comparable between the two randomised groups. Conclusions/interpretation Meal sequence can play a role in postprandial glucose control through both delayed gastric emptying and enhanced incretin secretion. Our findings provide clues for medical nutrition therapy to better prevent and manage type 2 diabetes.