Impact of Psychological Distress on Physiological Indicators of Healing Prognosis in Patients with Chronic Diabetic Foot Ulcers: A Longitudinal Study.

Objective: Diabetic foot ulcers (DFUs) are devastating complications of diabetes, responsible for a high number of amputations worldwide. Due to its impact on chronic inflammation, psychological distress may negatively impact the healing process. Thus, this study evaluated the influence of psychological distress on physiological indicators of healing prognosis and the potential of stress-reducing therapies for DFU healing. Approach: Patients with chronic DFU were recruited and assessed at enrollment and two months later. According to psychological scores at enrollment, participants were allocated into groups without (group 1) or with (group 3) psychological distress . Participants who reported clinical distress were then randomly allocated into a control (no stress-reducing intervention - group 4) or experimental (with stress-reducing interventions - group 5) group. Subsequently, indicators of healing prognosis were measured. Results: Groups 1 and 3 presented no differences in the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) score, glycated hemoglobin (HbA1c) or inflammatory and angiogenic markers. However, the immune cell ratio was increased by more than 2-fold in group 3, compared to group 1. Importantly, the expression of circulating microRNAs was significantly increased in group 3 [miR-21-5p, miR-155-5p, miR-146a-5p, and miR-221-3p ( p <0.05)], compared to group 1. Two months later, group 5 displayed a significant improvement in the Perceived Stress Scale (PSS) and Hospital Anxiety and Depression Scale (HADS) scores ( p <0.01), and the immune cell ratio was decreased by more than 2.5-fold. Innovation: This study helped to identify which variables and psychological interventions are more successful in promoting DFU healing. Conclusion: Psychological distress influenced clinical and physiological parameters, leading to compromised DFU healing and consequently underlining the potential of adjuvant stress-reducing approaches.