Abstract
BackgroundA 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.MethodsThis 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.ResultsUsing 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.ConclusionThe 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.
Highlights
A key feature of metabolic health is the ability to adapt upon dietary perturbations
Young and leaner subjects showed higher phenotypic flexibility in all health domains when compared to elderly subjects with higher adiposity To investigate if male and female subjects of higher age (60–70 years of age) and normal to high body fat percentage would respond differently to PhenFlex test” (PFT) as compared to young subjects (20–30 years of age) with low to normal body fat percentage, we used the health space methodology
As the importance further declines, features which serve as common biomarkers in type 2 diabetes mellitus (T2D) appear (4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, fasting glucose, Matsuda index, and positive area under the curve (AUC) for insulin) that all have higher concentrations in the “reduced phenotypic flexibility” group
Summary
A key feature of metabolic health is the ability to adapt upon dietary perturbations. A standardized optimal nutritional challenge test was defined after the performance of a systematic literature review [5], which was named the “PhenFlex test” (PFT) This “PhenFlex test” was characterized, van den Broek et al Genes & Nutrition (2017) 12:32 where 132 parameters were quantified during the 8-h response time course, that report on 26 metabolic processes distributed over seven organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress [6]. It was demonstrated that the PFT and defined new biomarkers are reliable in discriminating metabolically impaired subjects with type 2 diabetes from healthy subjects, since it was a more sensitive, early, and meaningful measure than the corresponding overnight fasting measure [6] For these reasons, the quantification of the response after a (nutritional) challenge may be a good alternative for the “classic (i.e., overnight fasting) biomarkers” in nutritional and health sciences. It is important to characterize the response to PFT in the healthy range of the population, ranging from an optimal towards a suboptimal response to the PFT as a measure of health
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