Ranges of phenotypic flexibility in healthy subjects

Abstract

Background: A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects.

Methods: This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, 100 healthy subjects were enrolled (50 males, 50 females) ranging in age (young, middle, old) and body fat percentage (low, medium, high), assuming variation in phenotypic flexibility. Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: flexibility in glucose, lipid, amino acid and vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was visualized using the "health space" by representing the four processes on the health space axes. By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized.

Results: Using the "health space" visualization, differences between groups as well as within groups from the healthy range of the population can be easily and intuitively assessed. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage.

Conclusion: The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice.

Keywords: Challenge test; Data visualization; Metabolic health; Nutritional challenge; Personalized health.

Fig. 1

Overview of the reference groups in the main health space, with both sexes included. Three spatial axes are labeled for the domain they represent. “AA-Vit” stands for amino acids and vitamins. Groups labeled using their respective age intervals as well as their body fat percentage intervals, L for low, N for normal, and H for high. The dot size represents the “metabolic stress” axis of the health space

Fig. 2

Boxplots for the two reference groups “optimal phenotypic flexibility” (green) and “reduced phenotypic flexibility” (red) as well as the values of the three outlier subjects (subjects 12, 52, and 73 shown in a red, blue, and yellow circle, respectively). Box shows the 25 to 75% interquartile range; whiskers indicate the maximum and minimum non-outlier values. Crossbar indicates the median values. Horizontal dotted line indicates cut-off values; levels above this line indicate abnormal clinical values. In waist, the lower dotted line represents cut-off values for female and the upper dotted line represents cut-off values for male; p indicates statistical significance after t test

Fig. 3

The main health space, with both sexes included. Three spatial axes are labeled for the domain they represent. “AA-Vit” stands for amino acids and vitamins. The dot size represents the “metabolic stress” axis of the health space. Groups labeled using their respective age intervals as well as their body fat percentage intervals, L for low, N for normal, and H for high. The three outlier subjects are encircled in green (subjects 12, 52, and 73)

Fig. 4

The combined health space including subjects from two different studies. Three spatial axes are labeled for the domain they represent. “AA-Vit” stands for amino acids and vitamins. The dot size represents the “metabolic stress” axis of the health space. Groups labeled using their respective age intervals as well as their body fat percentage intervals, L for low, N for normal, and H for high. The male outlier (subject 12) from the first health space is again encircled in green

Fig. 5

FlexScore distribution per study group. Box shows the interquartile range (IQR) with the median. The line indicates the range of observations within the ± 1.5 × IQR. Groups labeling used the respective age intervals as well as their body fat percentage intervals, L for low, N for normal, and H for high