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 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.
The authors thank Dr. Margarida Lima and Dr. João Moura for expertise and assistance in immunophenotyping and cellular analysis studies at the Cytometry Laboratory from the Centro Hospitalar do Porto, E.P.E. The authors also than André Louro and Gabriela Ferreira for their valuable participation for data collection, as well as Aryane Pinho and Isadora Pombeiro for sample transportation. The Graphical Abstract was created in the web application BioRender.com (Biorender.com, accessed onMarch 27, 2023).
This study was supported by FCT— Fundação para a Ciência e Tecnologia, through the Portuguese State Budget UIDB/01662/2020 assigned to PI (M.G.P.); COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI-01-0145-FEDER 028163) under the project PTDC/PSI-GER/28163/2017 assigned to PI (M.G.P.) and co PI (E.C.), and by the SPD—Sociedade Portuguesa de Diabetologia, through the awards Bolsa Luís Marques 2019 and 2020. This study was also financed by ERDF—European Regional Development Fund, through Centro 2020 Regional Operational Pro gramme under the project CENTRO-01-0145- FEDER-000012-HealthyAging2020 and through COMPETE 2020— Operational Programme for Competitiveness and Internationalization, Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, I.P., under projects POCI01-0145-FEDER-007440, UIDB/04539/2020,
UIDP/04539/2020, and LA/P/0058/2020, and Ph.D. grants 2020.04990.BD ( J.D.S.) and SFRH/BD/144199/2019 (D.S.).