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Metabolites
Volume 16
Issue 9
10.3390/metabo16090687
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Article

Exercise Metabolomics Reveals Intensity-Dependent Metabolic Responses Associated with Cardiorespiratory Fitness in Adults with Type 1 Diabetes

by
Olivia M. McCarthy
1,2,*,
Clara Solà
1,
Chloe Nicholas
1,2,
Sandra Tawfik
1,
Merete Bechmann Christensen
1,
Signe Schmidt
1,
Kirsten Nørgaard
1,3,
Richard M. Bracken
2,4 and
Marietta Kokla
1
1
Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, 2730 Herlev, Denmark
2
Applied Sport, Technology, Exercise and Medicine Research Centre, Faculty of Science and Engineering, Swansea University, Bay Campus, Fabian Way, Swansea SA1 8EN, UK
3
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
4
Health Technology and Solutions Interdisciplinary Research Institute, Faculty of Science and Engineering, Swansea University, Bay Campus, Fabian Way, Swansea SA1 8EN, UK
*
Author to whom correspondence should be addressed.
Metabolites 2026, 16(9), 687; https://doi.org/10.3390/metabo16090687 (registering DOI)
Submission received: 31 July 2026 / Revised: 10 September 2026 / Accepted: 14 September 2026 / Published: 18 September 2026
(This article belongs to the Special Issue Metabolic Responses to Exercise Training)
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Abstract

Purpose: To characterize plasma metabolomic responses to maximal exercise and their associations with cardiorespiratory fitness (CRF) in adults with type 1 diabetes. Methods: In this exploratory pooled secondary analysis, 21 adults (67% female; age, 51.6 ± 13.2 years; HbA1c, 67.5 ± 7.0 mmol/mol) completed a cycle-ergometer test to exhaustion; metabolomic data were available for 20. Plasma collected at rest, anaerobic threshold (AT), peak exercise, and recovery underwent targeted and untargeted gas chromatography–mass spectrometry profiling. Peak oxygen uptake (V̇O2peak) quantified CRF. Linear mixed-effects models adjusted for age, sex, HbA1c, and diabetes duration. Results: At the AT, L-(+)-lactic acid and 2-hydroxyisobutyric acid increased relative to rest (both q ≤ 0.010). Peak exercise produced changes in glycolytic, tricarboxylic acid (TCA)-cycle, and purine metabolites, with enrichment of the TCA cycle and nucleotide metabolism. TCA-cycle enrichment persisted during recovery. In exploratory interaction analyses, higher V̇O2peak was associated with increases in L-(+)-lactic acid at AT (β = 0.032, q = 0.040) and peak exercise (β = 0.031, q = 0.024), and in malic acid at peak exercise (β = 0.063, q = 0.010) and recovery (β = 0.061, q = 0.015). Conclusions: These preliminary findings suggest the presence of intensity-dependent and fitness-associated metabolic responses to exercise in adults with type 1 diabetes. Given the small sample size, particularly for interaction analyses, these findings require confirmation in larger independent cohorts.
Keywords: cardiorespiratory fitness; energy metabolism; exercise physiology; metabolomics; type 1 diabetes cardiorespiratory fitness; energy metabolism; exercise physiology; metabolomics; type 1 diabetes
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MDPI and ACS Style

McCarthy, O.M.; Solà, C.; Nicholas, C.; Tawfik, S.; Christensen, M.B.; Schmidt, S.; Nørgaard, K.; Bracken, R.M.; Kokla, M. Exercise Metabolomics Reveals Intensity-Dependent Metabolic Responses Associated with Cardiorespiratory Fitness in Adults with Type 1 Diabetes. Metabolites 2026, 16, 687. https://doi.org/10.3390/metabo16090687

AMA Style

McCarthy OM, Solà C, Nicholas C, Tawfik S, Christensen MB, Schmidt S, Nørgaard K, Bracken RM, Kokla M. Exercise Metabolomics Reveals Intensity-Dependent Metabolic Responses Associated with Cardiorespiratory Fitness in Adults with Type 1 Diabetes. Metabolites. 2026; 16(9):687. https://doi.org/10.3390/metabo16090687

Chicago/Turabian Style

McCarthy, Olivia M., Clara Solà, Chloe Nicholas, Sandra Tawfik, Merete Bechmann Christensen, Signe Schmidt, Kirsten Nørgaard, Richard M. Bracken, and Marietta Kokla. 2026. "Exercise Metabolomics Reveals Intensity-Dependent Metabolic Responses Associated with Cardiorespiratory Fitness in Adults with Type 1 Diabetes" Metabolites 16, no. 9: 687. https://doi.org/10.3390/metabo16090687

APA Style

McCarthy, O. M., Solà, C., Nicholas, C., Tawfik, S., Christensen, M. B., Schmidt, S., Nørgaard, K., Bracken, R. M., & Kokla, M. (2026). Exercise Metabolomics Reveals Intensity-Dependent Metabolic Responses Associated with Cardiorespiratory Fitness in Adults with Type 1 Diabetes. Metabolites, 16(9), 687. https://doi.org/10.3390/metabo16090687

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