Predictors of Unfavorable Outcomes in Diabetic Foot Ulcers

Background/Objectives: The aim of this study was to identify systemic, metabolic, and host-related prognostic factors for long-term outcomes in patients with a diabetic foot ulcer (DFU). Methods: One hundred patients were selected from a high-risk cohort of 426 individuals with a DFU (January 2021–January 2023) based on predefined inclusion and exclusion criteria. Clinical, laboratory, and imaging data were collected. Outcomes were categorized as favorable (healing) or unfavorable (non-healing, re-ulceration, amputation, or death). Prognostic factors were analyzed using random forest and categorical boosting models, with SHAP values to determine the importance of individual predictors. Results: The median age of participants was 65 years (interquartile range [IQR], 57–69.25), and the median duration of diabetes was 18 years (IQR, 12–26). Over a mean 2.1-year follow-up, unfavorable outcomes occurred in 53% of the whole cohort and in 36% of survivors. The strongest predictors of poor prognosis were prior amputation, elevated inflammatory markers, reduced eGFR, and dyslipidemia. Triglycerides showed a U-shaped association with outcomes. A lower BMI and shorter diabetes duration paradoxically were also linked to poorer prognosis. Glycemic control, comorbidities, and local foot characteristics had limited predictive value. Conclusions: Long-term DFU prognosis is driven mainly by systemic and host-related factors rather than by ulcer characteristics alone. Inflammation, renal dysfunction, dyslipidemia—particularly triglycerides—and prior amputation were the strongest predictors of unfavorable outcomes.