Does Physiological Stress Slow Down Wound Healing in Patients with Diabetes?

Background: Poor healing is an important contributing factor to amputation among patients with diabetic foot ulcers (DFUs). Physiological stress may slow wound healing and increase susceptibility to infection. Objectives: The objective was to examine the association between heart rate variability (HRV) as an indicator of physiological stress response and healing speed (Heal_Speed) among outpatients with active DFUs. Design and Methods: Ambulatory patients with diabetes with DFUs (n = 25, age: 59.3 ± 8.3 years) were recruited. HRV during pre-wound dressing was measured using a wearable sensor attached to participants' chest. HRVs were quantified in both time and frequency domains to assess physiological stress response and vagal tone (relaxation). Change in wound size between two consecutive visits was used to estimate Heal_Speed. Participants were then categorized into slow healing and fast healing groups. Between the two groups, comparisons were performed for demographic, clinical, and HRV derived parameters. Associations between different descriptors of HRV and Heal_Speed were also assessed. Results: Heal_Speed was significantly correlated with both vagal tone (r = -.705, P =.001) and stress response (r =.713, P =.001) extracted from frequency domain. No between-group differences were observed except those from HRV-derived parameters. Models based on HRVs were the highest predictors of slow/fast Heal_Speed (AUC > 0.90), while models based on demographic and clinical information had poor classification performance (AUC = 0.44). Conclusion: This study confirms an association between stress/vagal tone and wound healing in patients with DFUs. In particular, it highlights the importance of vagal tone (relaxation) in expediting wound healing. It also demonstrates the feasibility of assessing physiological stress responses using wearable technology in outpatient clinic during routine clinic visits.