Reproducibility and determinants of the metabolic responses during a mixed‐meal tolerance test

Author:

Stinson Emma J.1ORCID,Piaggi Paolo12ORCID,Mitchell Cassie M.1ORCID,Redman Leanne M.3ORCID,Krakoff Jonathan1

Affiliation:

1. 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

2. Department of Information Engineering University of Pisa Pisa Italy

3. Pennington Biomedical Research Center Baton Rouge Louisiana USA

Abstract

AbstractObjectiveThe aim of this study was to assess the reproducibility and physiological determinants of mixed‐meal tolerance tests (MMTTs) on glucose and insulin responses.MethodsWhile 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).ResultsIn 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).ConclusionsReproducibility 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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Wiley

Subject

Nutrition and Dietetics,Endocrinology,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)

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