Rui Carvalho

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.

Diabetic foot ulcer location is a known independent predictor for cure with a better healing gradient proximal to distal. Although advanced age is one of the main factors associated with greater diabetic foot ulcer severity, there are no studies evaluating diabetic foot ulcer location specifically in the elderly population in an outpatient setting. This study evaluated diabetic foot ulcer location and age-group interactions in diabetic foot presentation. A retrospective cohort study including adult patients with diabetic foot ulcers observed on their first visit to our center's Diabetic Foot Unit in 2018, divided into younger adults (YA) (18 to 64 years) and older adults (OA) (≥65 years). A total of 435 patients were included in the study with 159 (36.6%) in the YA, and 276 (63.4%) in the OA group. Neuro-ischemic diabetic foot ulcers were more frequent in the OA group (71.4% vs 43.4%, p<0.001). The number of patients with a history of diabetic foot ulcers was lower in the OA group (18.1% vs 25.2%, p=0.03). A smaller proportion of forefoot diabetic foot ulcers (74.9% vs 86.2%, p=0.007) and plantar location diabetic foot ulcers (9.4% vs 24.5%, p<0.001) occurred in the OA group. By univariate logistic regression analysis, we found two associations with older age: proximal (odds ratio (OR) 2.09 (1.23-3.53), p=0.006), and non-plantar (OR 3.13 (1.82-5.37), p<0.001) diabetic foot ulcer location. After adjusting for potential confounders in a multivariate analysis, older age lost the association to more proximal (OR 1.72 (0.94-3.15), p=0.081) and non-plantar (OR 1.78 (0.83-3.77), p=0.133) diabetic foot ulcer location. There are essential age differences in diabetic foot ulcer presentation. The OA group more frequently presents neuro-ischemic diabetic foot ulcers with more proximal and non-plantar locations.