Diabetic Peripheral Arterial Disease Versus Thromboangiitis Obliterans: A Multidimensional Comparison of Clinical Phenotype, Biomarkers, and Outcomes

<b>Objective</b>: This study aimed to compare thromboangiitis obliterans (TAO) and diabetic peripheral vascular disease (DPVD), the two major causes of distal limb ischemia, within a single analytical framework. The comparison was not limited to practical biomarkers that could support differential diagnosis but was based on multidimensional parameters that determine the clinical spectrum and prognosis. The two cohorts were systematically evaluated in terms of demographics and comorbidity burden, clinical presentation and limb involvement pattern, ulcer prevalence and localization, real-life treatment strategies (medical, endovascular, and surgical), and hard clinical endpoints (major/minor amputation, hospitalization, and all-cause mortality). DPVD was phenotyped according to the lesion level as isolated distal, isolated proximal, or multilevel. Within this framework, the isolated distal diabetic peripheral vascular disease (d-DPVD) subgroup was analyzed to determine how it differs from TAO in terms of clinical course, treatment patterns, and outcomes, despite the distal anatomical similarity. <b>Methods:</b> In this single-center retrospective cohort study, conducted between June 2019 and June 2025, 120 non-diabetic patients who met the angiographic TAO criteria were compared with 395 patients with DPVD with infrapopliteal/pedal atherosclerotic involvement. Clinical characteristics, ulcer topography, treatment strategies, and outcomes were recorded. The discriminatory value of the blood count and lipid-based inflammatory/atherogenic indices were evaluated using logistic regression and receiver operating characteristic (ROC) curve analyses. Additionally, a separate subgroup analysis was performed for the d-DPVD subgroup, which was considered the closest to the TAO phenotype in this study design. <b>Results</b>: Patients with DPVD were significantly older than those with TAO (61.1 ± 12.1 vs. 39.7 ± 7.9 years; <i>p</i> < 0.001), and male predominance was more pronounced in the TAO group (94.2% vs. 84.8%). Compared with TAO, DPVD was associated with a higher cardiometabolic comorbidity burden and increased inflammatory and atherogenic indices. Although the overall ulcer prevalence was comparable, DPVD more frequently presented with plantar or proximal ulcers confined to a single extremity, whereas TAO was characterized by bilateral or multi-extremity involvement and distal acral ulceration. Antiplatelet and statin therapy, revascularization, and rates of major amputation, all-cause mortality, and hospitalization were higher in patients with DPVD (all <i>p</i> < 0.05). On multivariate analysis, age, cumulative smoking exposure, SIRI, and CRI-I independently distinguished DPVD from TAO (all <i>p</i> < 0.05). In the isolated distal DPVD subgroup, despite similar distal anatomy, inflammatory/atherogenic burden, and overall clinical risk remained adverse. <b>Conclusions:</b> TAO and DPVD are two distinct phenotypes with different pathobiologies and prognoses, despite similar distal ischemia presentations. Simple inflammatory and atherogenic composite indices, evaluated in conjunction with clinical/ulcer patterns, may support the differential diagnosis and risk stratification of patients with peripheral arterial disease (PAD). However, prospective multicenter validation of these findings is required to confirm the results.