Combined PDGF and ANGPTL4 in diabetic foot: diagnostic value and exploratory early changes after plantar arch...

To evaluate the diagnostic value of combined platelet-derived growth factor (PDGF) and angiopoietin-like protein 4 (ANGPTL4) for distinguishing diabetic foot (DF) from diabetes mellitus (DM) without DF, and to explore their early changes following treatment initiation and their associations with 3-month ulcer healing.

Clinical data were retrospectively collected from January 2024 to May 2025. Before propensity score matching (PSM), 153 patients with DF and 116 non-DF DM patients met the eligibility criteria; after 1:1 PSM, 97 patients were retained in each group. Serum PDGF and ANGPTL4 were measured at baseline in both groups, with additional measurements taken on day 5 after the initiation of plantar arch angioplasty (PAA) and alprostadil in the DF group. The primary analysis evaluated the diagnostic performance of the baseline biomarkers using receiver operating characteristic (ROC) curves, while secondary exploratory analyses assessed their day-5 changes and associations with 3-month ulcer healing.

At baseline, PDGF was 26.23% lower and ANGPTL4 was 32.22% higher in the DF group than in the matched DM group (both P<0.05). The combined baseline model yielded an area under the curve (AUC) of 0.805, surpassing the performance of either biomarker alone. Both biomarkers were also associated with ulcer size, Wagner grade, fasting plasma glucose, and hemoglobin A1c. On day 5 after PAA and alprostadil initiation, PDGF significantly increased and ANGPTL4 significantly decreased relative to baseline (both P<0.05). At 3 months, 66 of 97 patients achieved complete ulcer healing; the combined day-5 model discriminated healing status with an AUC of 0.764, a sensitivity of 59.09%, and a specificity of 87.10%.

The combination of baseline PDGF and ANGPTL4 improved DF discrimination compared with either biomarker alone. Their day-5 changes and associations with 3-month ulcer healing were exploratory and should not be interpreted as evidence of treatment efficacy or validated prognostic utility.