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. 2026 Mar;69(3):618-630.
doi: 10.1007/s00125-025-06619-9. Epub 2025 Dec 9.

Impact of cardiovascular autonomic neuropathy on cardiopulmonary, sympathoadrenal and metabolic responses to physical exercise in adults with type 1 diabetes

Olivia M McCarthy  1   2 , Rasmus B Brødsgaard  3   4 , Sandra Tawfik  3 , Sissel Banner Lundemose  3   4 , Emilie B Lindkvist  3   4 , Sara H Naaman  3 , Christian Stevns Hansen  3 , Richard M Bracken  5   6 , Kirsten Nørgaard  3   4
Affiliations

Impact of cardiovascular autonomic neuropathy on cardiopulmonary, sympathoadrenal and metabolic responses to physical exercise in adults with type 1 diabetes

Olivia M McCarthy et al. Diabetologia. 2026 Mar.

Abstract

Aims/hypothesis: The aim of this work was to compare the cardiopulmonary, sympathoadrenal and metabolic responses to physical exercise in adults with type 1 diabetes with or without cardiovascular autonomic neuropathy (CAN).

Methods: Data collected during a graded maximal exercise test (GXT) from 24 participants with type 1 diabetes and CAN were compared against 24 matched control individuals without CAN (NO CAN). Throughout exercise, integrated cardiopulmonary variables were obtained continuously via spiroergometry. Plasma concentrations of adrenaline (epinephrine), noradrenaline (norepinephrine), glucose (PG) and lactate (PLa) were measured in 3 min intervals during exercise as well as at the peak workload. Data were assessed via independent t tests and two-factor ANOVAs with significance accepted at p≤0.05.

Results: Participants with CAN displayed a reduced V ˙ O 2 peak (CAN 19.6 ± 5.4 vs NO CAN 27.5 ± 7.8 ml kg-1 min-1) as well as attenuations in several other cardiopulmonary, lactate and exercise performance variables during GXT. Peak catecholamine concentrations were lower in CAN vs NO CAN (AD 0.17 ± 0.12 vs 0.38 ± 0.27 ng/ml, p=0.002; NAD 1.86 ± 1.04 vs 2.85 ± 1.23 ng/ml, p=0.007) as were the magnitudes of change in hormonal concentrations from rest to peak workloads (adrenaline Δ +0.13 ± 0.12 vs Δ +0.32 ± 0.24 ng/ml, p=0.005; noradrenaline Δ +1.33 ± 0.89 vs Δ +2.33 ± 1.30 ng/ml, p=0.005). PG concentrations throughout exercise were similar between groups and remained unchanged from rested values irrespective of CAN status.

Conclusions/interpretation: In adults with type 1 diabetes, CAN was associated with exercise intolerance characterised by impairments in various cardiopulmonary, sympathoadrenal system and metabolic responses to GXT. These data support uncovering the presence of CAN when prescribing a personalised physical training plan.

Keywords: Cardiopulmonary exercise testing; Cardiovascular autonomic neuropathy; Exercise; Graded exercise testing; Type 1 diabetes.

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Conflict of interest statement

Acknowledgements: The authors would like to thank the participants for their willingness to contribute and commit to the study protocol. Data availability statement: The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: OMc, RBB, CSH, RMB and KN contributed to the conception and design of the study. OMc, RBB, ST, SBL, EBL and SHN contributed to the acquisition of data. OMc, ST and RMB were responsible for data analyses. All authors were responsible for data interpretation. OMc wrote the original draft of the manuscript. All authors contributed to revising the article. All authors provided final approval of the version to be published. KN is responsible for the integrity of the work as a whole.

Figures

Fig. 1
Fig. 1
Plasma adrenaline (a) and noradrenaline (b) concentrations at various GXT stages, as well as their respective correlation with V˙O2peak values when expressed as a change from rest to peak workload (c, d) and the corresponding change in HR from rest to peak (e, f). In (a, b) white circles and squares represent a significant difference in the point concentration of a biomarker relative to the within-cohort value taken at rest (i.e. before commencing exercise). *p≤0.05 for CAN vs NO CAN point concentration of a biomarker. Data are presented as mean ± SEM
Fig. 2
Fig. 2
PG (a) and PLa (b) concentrations at various stages of GXT. White circles and squares represent a significant difference in the point concentration of a biomarker relative to the within-cohort value taken at rest (i.e. before commencing exercise). *p≤0.05 for CAN vs NO CAN point concentration of a biomarker. Data are presented as mean ± SEM
See this image and copyright information in PMC

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