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 2 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 score, glycated hemoglobin, or inflammatory and angiogenic markers. However, the immune cell ratio was increased by more than twofold in group 3, compared with 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 with group 1. Two months later, group 5 displayed a significant improvement in the Perceived Stress Scale and Hospital Anxiety and Depression Scale 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.
Keywords: diabetic foot ulcers; immune cell populations; impaired healing; microRNAs; psychological distress; stress-reducing therapies.