Kuwata Hitoshi, Iwasaki Masahiro, Shimizu Shinobu, Minami Kohtaro, Maeda Haruyo, Seino Susumu, Nakada Koji, Nosaka Chihiro, Murotani Kenta, Kurose Takeshi, Seino Yutaka, Yabe Daisuke
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, 1-5-6 Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan.
Diabetologia. 2016 Mar;59(3):453-61. doi: 10.1007/s00125-015-3841-z. Epub 2015 Dec 24.
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.
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, HbA1c 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 (13)C-acetate breath test involving measurement of (13)CO2 in breath samples collected before and after ingestion of rice steamed with (13)C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment.
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 × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 ± 72.3 mmol/l × min, MR 1,389.7 ± 69.4 mmol/l × min, RF 1,483.9 ± 72.8 mmol/l × min) 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 × min, MR 7,743.6 ± 801.4 pmol/l × min, RF 6,189.9 ± 581.3 pmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 ± 324.6 pmol/l × min, MR 4,897.7 ± 330.7 pmol/l × min, RF 3,747.5 ± 572.6 pmol/l × min [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-15-240 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.
UMIN Clinical Trials Registry UMIN000017434.
Japan Society for Promotion of Science, Japan Association for Diabetes Education and Care, and Japan Vascular Disease Research Foundation.
目的/假设：糖尿病饮食疗法的研究主要集中在进餐量和食物构成方面；而关于进餐顺序对餐后血糖管理影响的研究较少。本研究旨在探讨先吃鱼或肉后吃米饭对餐后血糖波动、胃排空及肠促胰岛素分泌的影响。
本实验为单中心、随机对照交叉探索性试验，在日本大阪一家私立医院的门诊病房进行。选取年龄在30 - 75岁之间、糖化血红蛋白（HbA1c）≤9.0%（75 mmol/mol）、体重指数（BMI）≤35 kg/m²的2型糖尿病患者（n = 12）和健康志愿者（n = 10），采用分层随机化方法将其平均分为两组，在三个不同的上午进行进餐顺序测试；第1天和第2天，交叉进行先吃米饭后吃鱼（RF）和先吃鱼后吃米饭（FR）的测试；第3天进行先吃肉后吃米饭（MR）的测试。分别评估进餐前后的血糖、胰岛素、C肽、胰高血糖素水平，以及胰高血糖素样肽 - 1（GLP - 1）和葡萄糖依赖性促胰岛素多肽水平。通过¹³C - 醋酸呼气试验测定胃排空率，该试验涉及测量摄入用¹³C标记的醋酸钠蒸制的米饭前后呼出气体样本中的¹³CO₂。参与者、进行测量或检查的人员以及评估结果的人员均知晓分组情况。
与RF相比，FR和MR可改善餐后血糖波动（2型糖尿病患者，15 - 240分钟血糖曲线下面积：FR为2326.6±114.7 mmol/l×min，MR为2257.0±82.3 mmol/l×min，RF为2475.6±87.2 mmol/l×min [FR与RF、MR与RF比较，p < 0.05]；健康受试者，FR为1419.8±72.3 mmol/l×min，MR为1389.7±69.4 mmol/l×min，RF为1483.9±72.8 mmol/l×min）及血糖变异性（2型糖尿病患者，15 - 240分钟血糖标准差：FR为1.94±0.22 mmol/l，MR为1.68±0.18 mmol/l，RF为2.77±0.24 mmol/l [FR与RF、MR与RF比较，p < 0.05]；健康受试者，FR为0.95±0.21 mmol/l，MR为0.83±0.16 mmol/l，RF为1.18±0.27 mmol/l）。FR和MR还可增强GLP - 1分泌，MR的作用强于FR或RF（2型糖尿病患者，15 - 240分钟GLP - 1曲线下面积：FR为7123.4±376.3 pmol/l×min，MR为7743.6±801.4 pmol/l×min，RF为6189.9±581.3 pmol/l×min [FR与RF、MR与RF比较，p < 0.05]；健康受试者，FR为3977.3±324.6 pmol/l×min，MR为4897.7±330.7 pmol/l×min，RF为3747.5±572.6 pmol/l×min [MR与RF、MR与FR比较，p < 0.05]）。FR和MR可延迟胃排空（胃排空50%时间：2型糖尿病患者，FR为83.2±7.2分钟，MR为82.3±6.4分钟，RF为29.8±3.9分钟 [FR与RF、MR与RF比较，p < 0.05]；健康受试者，FR为66.3±5.5分钟，MR为74.4±7.6分钟，RF为32.4±4.5分钟 [FR与RF、MR与RF比较，p < 0.05]），这与餐后血糖波动的改善（2型糖尿病患者，15 - 120分钟血糖曲线下面积：r = -0.746，p < 0.05；健康受试者，r = -0.433，p < 0.05）、血糖变异性的改善（2型糖尿病患者，15 - 240分钟血糖标准差：r = -0.
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