Roughly half of all people who present with a diabetes-related foot ulcer also have peripheral artery disease (PAD), and its presence substantially raises the risk of non-healing, amputation, and cardiovascular death. Yet PAD in diabetes is frequently under-recognized, partly because the neuropathy that accompanies it masks the classic warning symptoms and partly because the bedside tests clinicians rely on behave differently in a diabetic limb. The 2023 intersocietal guideline produced jointly by the International Working Group on the Diabetic Foot (IWGDF), the European Society for Vascular Surgery, and the Society for Vascular Surgery consolidated the evidence on this problem into twenty-five graded recommendations covering diagnosis, prognosis, and treatment.
Why Peripheral Artery Disease Is Harder to Detect in Diabetes
Medial arterial calcification stiffens the tibial vessels in long-standing diabetes, which can push ankle pressures artificially high and produce a falsely reassuring ankle-brachial index (ABI). A systematic review by Forsythe and colleagues, prepared for the IWGDF and published in Diabetes/Metabolism Research and Reviews in 2020, examined fifteen studies comparing bedside tests against reference imaging. The reviewers found that an ABI below 0.9 usefully raises suspicion of PAD (positive likelihood ratio 6.5), but a value in the normal 0.9–1.3 range does not exclude it (negative likelihood ratio 0.31).
Several alternatives performed better at ruling disease out. A toe-brachial index above 0.75 made PAD less likely (negative likelihood ratio 0.14–0.24), and triphasic tibial Doppler waveforms had the strongest performance for exclusion (negative likelihood ratio 0.09–0.28), although this was assessed in only two studies. Pulse palpation alone was insufficient: clinical examination without adjunctive testing could not reliably exclude PAD (negative likelihood ratio 0.75).
What This Means in Practice
The guideline recommendation that follows from this evidence is that every person with diabetes and a foot ulcer should undergo clinical assessment plus bedside vascular testing, and that a non-healing ulcer should prompt further vascular imaging regardless of what the bedside results showed. The Australian adaptation of these recommendations, published by Chuter and colleagues in the Journal of Foot and Ankle Research in 2022, adopted sixteen of the seventeen original IWGDF recommendations and made this point explicitly.
Staging the Limb: The WIfI Classification
Once ischaemia is identified, the question becomes how threatened the limb actually is. The Society for Vascular Surgery’s Wound, Ischaemia, and foot Infection (WIfI) system grades each of those three variables and combines them into a clinical stage. A systematic review and meta-analysis by van Reijen and colleagues in the European Journal of Vascular and Endovascular Surgery (2019) pooled twelve studies comprising 2,669 patients. Estimated one-year major amputation rates rose steeply across stages: 0% for stage I, 8% for stage II, 11% for stage III, and 38% for stage IV. The authors noted that most included studies were retrospective and of moderate quality, so WIfI is best understood as a prognostic aid rather than a treatment algorithm.
Choosing a Revascularization Strategy: Two Landmark Trials
For years the choice between open bypass and endovascular treatment in chronic limb-threatening ischaemia rested on observational data. Two randomized trials have since reported, and they did not point in the same direction.
BEST-CLI, published by Farber and colleagues in the New England Journal of Medicine in 2022, randomized patients to surgical bypass or endovascular therapy. In cohort 1 — patients with an adequate single-segment great saphenous vein available — a major adverse limb event or death occurred in 42.6% of the surgical group versus 57.4% of the endovascular group over a median 2.7 years (hazard ratio 0.68; 95% CI 0.59–0.79). In cohort 2, comprising patients without suitable vein, the difference was not statistically significant (hazard ratio 0.79; 95% CI 0.58–1.06).
BASIL-2, reported by Bradbury and colleagues in The Lancet in 2023, studied a narrower population: 345 patients who required an infrapopliteal revascularization. Here a vein-bypass-first strategy was associated with worse amputation-free survival than a best-endovascular-treatment-first strategy (adjusted hazard ratio 1.35; 95% CI 1.02–1.80), driven largely by deaths, most of them cardiovascular.
The apparent conflict is best explained by differences in the populations studied and the anatomy treated. A companion cohort study by Popplewell and colleagues (2023) found that patients randomized into BASIL-2 represented only about 4% of consecutive limb-threatening ischaemia admissions at one academic centre, with most excluded for anatomical or technical reasons — a caution against generalizing either trial too broadly.
The Systemic Dimension
PAD in a diabetic foot is a marker of widespread atherosclerosis. In both trials, cardiovascular events were the leading cause of death. The intersocietal guideline therefore pairs its revascularization recommendations with intensive cardiovascular risk management and recommends that centres treating these ulcers have expertise in, or rapid access to, the facilities needed to diagnose and treat PAD, with multidisciplinary follow-up after intervention.
Summary
PAD accompanies about half of diabetes-related foot ulcers and materially worsens outcomes. Bedside testing is necessary but imperfect: a normal ABI does not exclude disease, toe pressures and Doppler waveforms perform better at ruling it out, and a non-healing ulcer warrants imaging regardless. WIfI staging stratifies one-year amputation risk across a wide range. Randomized evidence supports open bypass when good-quality vein is available for infrainguinal disease, while endovascular-first strategies performed better in the infrapopliteal population studied in BASIL-2 — a reminder that revascularization decisions depend heavily on anatomy, conduit availability, and overall patient risk.
References
- Fitridge R, Chuter V, Mills J, et al. The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes mellitus and a foot ulcer. European Journal of Vascular and Endovascular Surgery. 2023;66(4):454–483. doi:10.1016/j.ejvs.2023.07.020
- Forsythe RO, Apelqvist J, Boyko EJ, et al. Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review. Diabetes/Metabolism Research and Reviews. 2020;36(S1):e3277. doi:10.1002/dmrr.3277
- van Reijen NS, Ponchant K, Ubbink DT, Koelemay MJW. The prognostic value of the WIfI classification in patients with chronic limb threatening ischaemia: A systematic review and meta-analysis. European Journal of Vascular and Endovascular Surgery. 2019;58(3):362–371. doi:10.1016/j.ejvs.2019.03.040
- Farber A, Menard MT, Conte MS, et al. Surgery or endovascular therapy for chronic limb-threatening ischemia. New England Journal of Medicine. 2022;387(25):2305–2316. doi:10.1056/NEJMoa2207899
- Bradbury AW, Moakes CA, Popplewell M, et al. A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial. The Lancet. 2023;401(10390):1798–1809. doi:10.1016/S0140-6736(23)00462-2
- Popplewell MA, Meecham L, Davies HOB, et al. Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL) prospective cohort study and the generalisability of the BASIL-2 randomised controlled trial. European Journal of Vascular and Endovascular Surgery. 2024;67(1):146–152. doi:10.1016/j.ejvs.2023.09.041
- Chuter V, Quigley F, Tosenovsky P, et al. Australian guideline on diagnosis and management of peripheral artery disease: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease. Journal of Foot and Ankle Research. 2022;15(1):51. doi:10.1186/s13047-022-00550-7
Bibliographic data for the cited articles were retrieved from PubMed.
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