1. Introduction
overweight or obesity, T2DM, prediabetes, diabetes
PREDIABETES, EVENTS, TYPE 2 DIABETES MELLITUS, INSULIN SENSITIVITY, DIABETES
These two authors contributed equally to this work.The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers the potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among participants with elevated T2DM risk to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary intervention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females and 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distinguish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.The global prevalence of type 2 diabetes mellitus (T2DM) is expected to reach 783.2 million (12.2%) in 2045 [Recent studies have revealed large inter-individual variations in plasma glucose after corresponding meals and found that gut microbiota and food structure are important determinants of the differential response [Clustering of dynamic features of the postprandial response could aid in identifying differences in glucose variability to the same dietary intake and provide a simple way of categorizing individuals according to diabetes risk. Such clusters may be targets for tailored diet and lifestyle interventions to prevent prediabetes or T2DM. Differential responders were identified after consuming an oral glucose tolerance test (OGTT) [Therefore, we aimed to investigate if a simple mechanistic model of glucose regulation could be applied to describe postprandial glucose concentrations after a standardized MMTT based on regular foods and whether clusters of differential responders could be identified from such a model. Furthermore, we investigated if differential response clusters are associated differently with risk factors of T2DM. We further investigated if baseline gut microbiota was associated with the response clusters and if clusters remained after dietary intervention with low or high glycemic index. The methodology was applied to data from non-diabetic men and women from Sweden, Italy, and the USA with overweight or obesity participating in interventions with high or low glycemic index (GI) Mediterranean diets [