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Published in: Diabetologia 7/2024

Open Access 25-04-2024 | Type 1 Diabetes | Article

The metabolome as a diagnostic for maximal aerobic capacity during exercise in type 1 diabetes

Authors: Guy S. Taylor, Kieran Smith, Jadine Scragg, Timothy J. McDonald, James A. Shaw, Daniel J. West, Lee D. Roberts

Published in: Diabetologia | Issue 7/2024

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Abstract

Aims/hypothesis

Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by \(\dot{V}{\text{O}}_{\text{2peak}}\).

Methods

Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3–200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by \(\dot{V}{\text{O}}_{\text{2peak}}\) test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% \(\dot{V}{\text{O}}_{\text{2peak}}\)) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity (\(\dot{V}{\text{O}}_{\text{2peak}}\)) during exercise in health and type 1 diabetes.

Results

Maximal aerobic capacity (\(\dot{V}{\text{O}}_{\text{2peak}}\)) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10−5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity (\(\dot{V}{\text{O}}_{\text{2peak}}\)) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]).

Conclusions/interpretation

The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.

Graphical Abstract

Appendix
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Literature
10.
go back to reference Goulding RP, Roche DM, Scott SN, Koga S, Weston PJ, Marwood S (2020) Limitations to exercise tolerance in type 1 diabetes: the role of pulmonary oxygen uptake kinetics and priming exercise. J Appl Physiol (1985) 128:1299–1309CrossRefPubMed Goulding RP, Roche DM, Scott SN, Koga S, Weston PJ, Marwood S (2020) Limitations to exercise tolerance in type 1 diabetes: the role of pulmonary oxygen uptake kinetics and priming exercise. J Appl Physiol (1985) 128:1299–1309CrossRefPubMed
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Metadata
Title
The metabolome as a diagnostic for maximal aerobic capacity during exercise in type 1 diabetes
Authors
Guy S. Taylor
Kieran Smith
Jadine Scragg
Timothy J. McDonald
James A. Shaw
Daniel J. West
Lee D. Roberts
Publication date
25-04-2024
Publisher
Springer Berlin Heidelberg
Keyword
Type 1 Diabetes
Published in
Diabetologia / Issue 7/2024
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-024-06153-0

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