When physical activity feels harder: cardiovascular autonomic neuropathy impairs physiologic responses to exercise in type 1 diabetes

Aims: The authors aimed to compare the cardiopulmonary, sympathoadrenal and metabolic responses to physical exercise in adults with type 1 diabetes (T1D) with or without cardiovascular autonomic neuropathy (CAN).

Methods: The study included 24 individuals (17 males) with T1D and confirmed CAN, along with 24 age-, sex- and BMI-matched controls with T1D but without CAN. Participants performed a graded maximal exercise testing (GXT) on a workload-controlled cycle ergometer until exhaustion (3 min rest, 3 min warm-up, 1 min increases in workload until volitional exhaustion, 3 min active and 3 min passive recovery). During exercise, cardiopulmonary (heart rate [HR] and oxygen consumption rate [VO2]), sympathoadrenal (plasma adrenaline and noradrenaline), and metabolic (plasma glucose [PG] and lactate [PLa]) parameters were measured.

Results: During GXT, participants with CAN showed significantly lower VO2, HR, minute ventilation and breathing frequency compared to those without CAN. At peak workload, plasma adrenaline and noradrenaline concentrations were lower in participants with CAN compared to those without CAN. In addition, compared to those without CAN, participants with CAN exhibited 84% and 55% lower increases in adrenaline and noradrenaline concentrations, respectively, from rest to peak workload. Peak VO2 predicted changes in adrenaline (p<0.001, R2=0.332) and noradrenaline (p=0.004, R2=0.186) levels from rest to peak. Strong positive correlations were found between the change in HR (ΔHR) from rest to peak workload and changes in both adrenaline (r=0.551, p<0.001) and noradrenaline (r=0.529, p<0.001) concentrations during exercise. No significant differences in PG levels were observed between participants with and without CAN, and PG levels remained stable throughout exercise. Participants with CAN showed lower PLa concentrations at all stages of GXT from the anaerobic threshold onwards compared with those without CAN.

Conclusions: In individuals with T1D, CAN was associated with reduced exercise capacity and impaired cardiopulmonary, sympathoadrenal and metabolic responses to GXT.

Comments: This study offers valuable insight into the impact of T1D-associated CAN on cardiopulmonary, sympathoadrenal, and metabolic responses to a graded maximal exercise test. By leveraging the physiologic stress elicited by incremental exercise, research in this area allows a better understanding of CAN pathophysiology. From a clinical perspective, exertional intolerance may represent an additional factor contributing to decreased functional capacity in individuals with CAN and should therefore be considered when developing personalized training plans. Furthermore, reduced cardiorespiratory fitness has well-documented prognostic significance in the general population (Lang JJ et al Br J Sports Med 2024; 58:556-566), which a diagnosis of CAN could help to uncover in individuals with T1D. However, this study is limited by its small sample size, cross-sectional design, and missing data on concomitant medications that could have affected the test results. Thus, larger prospective studies are needed to clarify the impact of CAN on exercise responses and cardiorespiratory fitness as well as to explore the potential of regular exercise training to slow its progression.

Pietro Pertile

Reference. McCarthy OM, Brødsgaard RB, Tawfik S, Lundemose SB, Lindkvist EB, Naaman SH, Hansen CS, Bracken RM, Nørgaard K. Impact of cardiovascular autonomic neuropathy on cardiopulmonary, sympathoadrenal and metabolic responses to physical exercise in adults with type 1 diabetes. Diabetologia. 2025 Dec 9. doi: 10.1007/s00125-025-06619-9. Epub ahead of print. PMID: 41364197.

🔗 https://link.springer.com/article/10.1007/s00125-025-06619-9