Evidence suggests that people react differently to the same diet due to inter-individual differences. However, few studies have investigated variation in response to dietary interventions based on individuals' baseline metabolic characteristics. This study aims to examine the differential reaction of metabotype subgroups to an OGTT and a dietary fiber intervention. We assigned 356 healthy participants of an OGTT sub-study and a 12-week dietary fiber intervention sub-study within the enable cluster to three metabotype subgroups previously identified in the KORA F4 study population. To explore the association between plasma glucose level and metabotype subgroups, we used linear mixed models adjusted for age, sex, and physical activity. Individuals in different metabotype subgroups showed differential responses to OGTT. Compared to the healthy metabotype (metabotype 1), participants in intermediate metabotype (metabotype 2) and unfavorable metabotype (metabotype 3) had significantly higher plasma glucose concentrations at 120 min after glucose bolus (β = 7.881, p = 0.005; β = 32.79, p < 0.001, respectively). Additionally, the linear regression model showed that the Area under the curve (AUC) of plasma glucose concentrations was significantly different across the metabotype subgroups. The associations between metabotype subgroups and metabolic parameters among fiber intervention participants remained insignificant in the multivariate-adjusted linear model. However, the metabotype 3 had the highest mean reduction in insulin, cholesterol parameters (TC, LDLc, and non-HDLc), and systolic and diastolic blood pressure at the end of the intervention period. This study supports the use of the metabotype concept to identify metabolically similar subgroups and to develop targeted dietary interventions at the metabotype subgroup level for the primary prevention of diet-related diseases.

The aim of metabotyping is to categorize individuals into metabolically similar groups. Earlier studies that explored metabotyping used numerous parameters, which made it less transferable to apply. Therefore, this study aimed to identify metabotypes based on a set of standard laboratory parameters that are regularly determined in clinical practice. K-means cluster analysis was used to group 3001 adults from the KORA F4 cohort into three clusters. We identified the clustering parameters through variable importance methods, without including any specific disease endpoint. Several unique combinations of selected parameters were used to create different metabotype models. Metabotype models were then described and evaluated, based on various metabolic parameters and on the incidence of cardiometabolic diseases. As a result, two optimal models were identified: a model composed of five parameters, which were fasting glucose, HDLc, non-HDLc, uric acid, and BMI (the metabolic disease model) for clustering; and a model that included four parameters, which were fasting glucose, HDLc, non-HDLc, and triglycerides (the cardiovascular disease model). These identified metabotypes are based on a few common parameters that are measured in everyday clinical practice. These metabotypes are cost-effective, and can be easily applied on a large scale in order to identify specific risk groups that can benefit most from measures to prevent cardiometabolic diseases, such as dietary recommendations and lifestyle interventions.