Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
Department of Information Engineering, University of Pisa, Pisa, Italy.
Obesity (Silver Spring). 2023 Mar;31(3):768-779. doi: 10.1002/oby.23678. Epub 2023 Feb 14.
The aim of this study was to assess the reproducibility and physiological determinants of mixed-meal tolerance tests (MMTTs) on glucose and insulin responses.
While inpatients on a weight-maintaining diet, 894 individuals (574 with normal and 267 with impaired glucose regulation and 53 with type 2 diabetes [T2D]) underwent 9-hour MMTTs (breakfast and lunch; 30% weight-maintaining diet each; 40% carbohydrate, 40% fat, and 20% protein). Total/incremental areas under the curve (AUC/iAUC) were calculated from MMTT plasma glucose/insulin concentrations. Acute insulin response (AIR) was quantified by intravenous glucose tolerance test and insulin action (M) via hyperinsulinemic-euglycemic clamp. A subset had repeat MMTTs (median follow-up = 1.4 years).
In individuals without T2D, for breakfast-versus-lunch reproducibility of glucose, AUCs were moderate (intraclass correlation coefficients [ICCs]: 0.44-0.61), and iAUCs were poor (ICCs < 0.15). For repeated MMTTs, reproducibility of AUC/iAUCs was low (ICCs: 0.11-0.36). For insulin, AUC reproducibility was high (ICCs > 0.70), and iAUCs were moderate (ICCs: 0.64-0.71). For repeated MMTTs, ICC AUC/iAUCs were 0.34 to 0.54. In those with T2D, ICC glucose AUC/iAUCs were >0.80 and >0.50, respectively, and for insulin were <0.40. For repeated MMTTs, ICC glucose/insulin AUC/iAUCs were moderate. Glucose AUCs associated with M/AIR (partial Rs < -0.25), and insulin AUCs negatively/positively associated with M/AIR (partial Rs = -0.51/0.24).
Reproducibility of glucose/insulin responses to MMTTs varied by subtraction of fasting values, glucose status, and time. Insulin secretion and action explained ~20% of MMTT responses. The substantial variability in MMTT response requires consideration in studies using MMTT outcomes.
本研究旨在评估混合餐耐量试验（MMTT）对葡萄糖和胰岛素反应的可重复性及其生理决定因素。
894 名住院患者在维持体重的饮食下进行 9 小时 MMTT（早餐和午餐；各占维持体重饮食的 30%；40%碳水化合物、40%脂肪和 20%蛋白质）。从 MMTT 血浆葡萄糖/胰岛素浓度计算总/增量曲线下面积（AUC/iAUC）。通过静脉葡萄糖耐量试验量化急性胰岛素反应（AIR），通过高胰岛素-正常血糖钳夹技术量化胰岛素作用（M）。部分患者进行了重复 MMTT（中位随访时间为 1.4 年）。
在无 2 型糖尿病的个体中，早餐与午餐的葡萄糖 AUC 重现性中等（组内相关系数 [ICC]：0.44-0.61），iAUC 重现性较差（ICC<0.15）。对于重复 MMTT，AUC/iAUC 的重现性较低（ICC：0.11-0.36）。对于胰岛素，AUC 重现性高（ICC>0.70），iAUC 重现性中等（ICC：0.64-0.71）。对于重复 MMTT，ICC AUC/iAUC 为 0.34 至 0.54。在有 2 型糖尿病的个体中，ICC 葡萄糖 AUC/iAUC 分别为>0.80 和>0.50，而胰岛素 AUC/iAUC 则<0.40。对于重复 MMTT，ICC 葡萄糖/胰岛素 AUC/iAUC 为中等。葡萄糖 AUC 与 M/AIR 呈负相关（部分 Rs<-0.25），而胰岛素 AUC 与 M/AIR 呈负相关/正相关（部分 Rs=-0.51/0.24）。
MMTT 对葡萄糖/胰岛素反应的重现性因空腹值、葡萄糖状态和时间的差异而不同。胰岛素分泌和作用解释了 MMTT 反应的约 20%。MMTT 反应的显著变异性需要在使用 MMTT 结果的研究中考虑。
