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Association of metabolic flexibility indexes after an oral glucose tolerance test with cardiometabolic risk factors

European Journal of Clinical Nutrition volume 78, pages 180–186 (2024)Cite this article

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Abstract

Background & aims

Metabolic flexibility (MetF) is considered a metabolic health biomarker, as excess body weight is associated with lower MetF. We aimed to identify whether MetF indexes were associated with cardiometabolic risk factors before and after adjustment for body size-related factors (body weight, fat-free mass, and resting metabolic rate).

Methods

We studied 51 participants (55% women; 33.6 ± 8.7 years; 26.3 ± 3.8 kg/m²) who consumed a 75-g glucose load. We measured gas exchange before (fasting) and for 3 h after glucose ingestion. MetF indexes were assessed, including the change after each hour and the 3-hour incremental area under the curve (iAUC) in respiratory exchange ratio (RER). These indexes were then related to cardiometabolic risk factors before and after adjusting for body size-related factors.

Results

MetF indexes correlated with each other (r ≥ 0.51; P < 0.001) and related to body weight (adjusted R2 ≥ 0.09; P < 0.03). A similar pattern was noted for fat-free mass and resting metabolic rate. MetF, regardless of the index, was not related to cardiometabolic risk factors except to BMI and high-density lipoprotein-cholesterol (HDL-C). The association between BMI and MetF disappeared after adjusting for body size-related factors. Similar adjustments did not modify the association between HDL-C and MetF, especially when approached by the change in RER after the first hour (adjusted R2 = 0.20–0.22; all P < 0.02).

Conclusions

Inter-individual body size differences fully accounted for the associations between BMI and MetF. However, variability in body size-related factors appeared less relevant in affecting the associations of other cardiometabolic risk factors with MetF.

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Fig. 1: Study design and different methods for computing the metabolic flexibility (MetF) in a single parameter (i.e., MetF indexes).
Fig. 2: Bland–Altman plots for metabolic determination among different methods.
Fig. 3: Associations between metabolic flexibility indexes and body-size-related factors.

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Data availability

Additional data are available from the corresponding author on reasonable request.

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Funding

Funding

This work was supported by ANID/CONICYT FONDECYT Regular 1130217 and 1220551. JMAA is supported by a Juan de la Cierva ─ Formación postdoctoral grant (Grant FJC2020-044453-I) funded by MCIN/AEI/ 10.13039/501100011033 and by “European Union NextGenerationEU/PRTR”.

Author information

Authors and Affiliations

  1. Institute for Innovation & Sustainable Food Chain Development, Department of Health Sciences, Public University of Navarre, Campus Arrosadía, s/n, 31006, Pamplona, Spain

    J. M. A. Alcantara

  2. Navarra Institute for Health Research, IdiSNA, Pamplona, Spain

    J. M. A. Alcantara

  3. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain

    J. M. A. Alcantara

  4. Department of Health Sciences, Nutrition and Dietetics Career, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    J. E. Galgani

  5. Department of Nutrition, Diabetes and Metabolism, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    J. E. Galgani

  6. Pennington Biomedical Research Center, Baton Rouge, LA, USA

    J. E. Galgani

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  1. J. M. A. Alcantara
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Contributions

The authors’ responsibilities were as follows – JEG: designed and supervised human experiments; principal responsibility for the final content. JEG: data collection of human experiments. JMAA: data analysis and interpretation. JMAA: writing the original draft. JMAA and JEG: critically revised the manuscript, discussed the results, and approved the final version. The authors report no conflicts of interest.

Corresponding authors

Correspondence to J. M. A. Alcantara or J. E. Galgani.

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The authors decalre no competing interests.

Ethical approval

The study was approved by the Committee for Research Involving Human Subjects of the Pontificia Universidad Católica de Chile.

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Alcantara, J.M.A., Galgani, J.E. Association of metabolic flexibility indexes after an oral glucose tolerance test with cardiometabolic risk factors. Eur J Clin Nutr 78, 180–186 (2024). https://doi.org/10.1038/s41430-023-01373-w

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