Clinical manifestations

Asymptomatic disease can be detected by noninvasive measures, such as the ABI.

However, in diabetic patients, studies based on ABI measurement may underestimate the prevalence of LEAD because in 30%–50% of the cases, ankle pressure is falsely elevated due to medial sclerosis (Lepäntalo et al. 2011, Faglia et al. 2009, Acin et al.

2014, Prompers et al. 2007). According to one estimate, two thirds of all patients with LEAD are asymptomatic (Aboyans et al. 2018). In Germany, 26% of diabetic and 13% of non-diabetic individuals aged over 65 years (median age 74 years) and visiting primary care for any cause had an ABI of < 0.9 (Lange et al. 2004). In Sweden, 29% of 68-year-old men with diabetes and 12% of those without diabetes had an ABI of < 0.9 (Ögren et al.

2005). Notably, patients with asymptomatic LEAD have an increased risk of cardiovascular complications, stroke, acute myocardial infarction and death (Sigvant et al. 2016).

2.2.1.2 CLAUDICATION

Claudication is ischaemic pain that starts when the muscles of the lower extremity are exercised, typically when walking. The pain is relieved by stopping exercise. The symptom is caused by insufficient blood flow to meet the increased demand of exercising muscles. In the Swedish general population, the prevalence was 7.1% in men and 6.6% in women with a median age of 71 years (Sigvant et al. 2007).

In diabetic patients, neuropathy may abolish the sensation of pain. However, diabetic patientss had a more than two-fold risk of claudication in a US study, in which prevalence of claudication in the general population was 0.9%–1.9% in men and 0.4%–1.1% in women, depending on age (45–84 years) (Murabito et al. 1997). Of diabetic patients, 5.1% had claudication, whereas the proportion of claudicants among non-diabetic patients was 2.1% in another study (Lange et al. 2004).

2.2.1.3 CRITICAL LIMB ISCHAEMIA /CHRONIC LIMB-THREATENING ISCHAEMIA

The term critical limb ischaemia was defined in 1982 to describe lower limb ischaemia that places the limb under the threat of amputation unless a revascularisation is performed (Jamieson 1982). The definitions have later varied (Table 1). Recently, the term chronic limb-threatening ischaemia (CLTI) has been adopted (Conte et al. 2019). A new category of “subcritical” ischaemia was proposed by Wolfe et al. in 1997 and later supported by the European Society for Vascular Surgery (Wolfe et al. 1997, Becker et al.

2011). Limbs threatened with amputation may need different efforts than limbs with delayed healing and non-healing of ulcers (Becker et al. 2011). Indeed, the WIfI classification presents 4 grades for ischaemia (Mills et al. 2014). It is estimated that the incidence of CLTI in the general population is 500–1 000/ 1 million inhabitants per year (Norgren et al. 2007).

Approximately half of the patients with DFU attending specialist clinics have ischaemia.

In the Eurodiale study, LEAD was found by means of ABI measurements in 22%–73% of the patients with a diabetic foot ulcer, depending on the centre, and a total of 49% of

22 these patients had an ABI of < 0.9 and/or non-palpable arteria tibialis posterior (ATP) and arteria dorsalis pedis ( ADP) pulses, while 12% had an ABI of < 0.5 (Schaper 2012).

In a Swedish study, 49% of the diabetic foot ulcers were neuroischaemic, based on an ankle pressure of < 80mmHg, a toe pressure of < 45 mmHg, or Wagner grades 4 and 5 whenever pressures were not obtained (Gershater et al. 2009). In a surgical series from a Helsinki University Hospital clinic, 50% of the patients undergoing infrainguinal bypass due to an ischaemic tissue lesion had diabetes mellitus (Söderström et al. 2008).

Table 1. Definition of CLI and CLTI (chronic limb-threatening ischaemia)

Jamieson 1982 Lower limb ischaemia that threatens the limb with amputation unless a revascularisation is performed.

Second European Consensus

TASC II (Norgren et al. 2007) Objectively proven arterial occlusive disease.

IWGDF and ESVS

recommendations (Cao et al.2011)

Ulcer healing is severely impaired if ABI <0.6. Values > 0.6 should not be trusted. Nevertheless, toe pressure and tcpO2 < 30mmHg would indicate severely impaired healing whereas toe pressure > 55 mmHg and tcpO2 >

50 mmHg would be favourable regarding healing.

Guidance by IWGDF on diabetic foot ulcer and peripheral arterial disease (Brownrigg et al. 2016)

The presence of ABI 0.9–1.3, toe brachial index ≥ 0.75, and the presence of triphasic pedal Doppler arterial waveforms largely exclude LEAD. Imaging studies and subsequent revascularisation should be considered if toe pressure is < 30 mmHg or TcPO2 < 25 mmHg, and if the ulcer is not healing in 6 weeks.

CLTI (Conte et al. 2019) Presence of LEAD in combination with rest pain, gangrene, or a lower limb ulceration with > 2 weeks’

duration. The role of accurate clinical classification is emphasised. WIfI classification is recommended.

ESVS European Society for Vascular Surgery, TASC Transatlantic Intersociety Consensus, IWGDF International Working Group for Diabetic Foot, LEAD lower extremity arterial disease, CLI (critical limb ischaemia), CLTI (chronic limb-threatening ischaemia)

2.2.1.4 DISTRIBUTION OF LEAD IN DIABETIC PATIENTS

In diabetic patients with foot ulcers or gangrene, atherosclerosis typically occludes and obstructs arteries below the knee and the arteria profunda femoris. The lesions are typically multilevel, often bilateral and are common both in men and women. (Jude et al. 2001, Diehm et al. 2006, Graziani et al. 2007, Apelqvist et al. 2011.) In 413 diabetic

patients undergoing endovascular treatment for CLTI, 7% had a > 50% stenosis only in the popliteal or more proximal arteries and 32% only in the infrapopliteal arteries, while 60% had both infrapopliteal and more proximal stenosis (Faglia et al. 2009). In a cohort of 1,046 diabetic patients with ischaemic foot ulcers, 314 (30%) patients underwent percutaneous transluminal angioplasty (PTA) and 190 (18%) vascular reconstruction. In 46% of the endovascular cases, the crural arteries were treated and 51% of the open-surgical reconstructions had truncal or lower run-off (Apelqvist et al. 2011). A cohort of ischaemic diabetic feet showed occlusion in 25% of the fibular arteries, in 56% of the posterior tibial arteries (ATP)s, in 53% of the anterior tibial arteries (ATA)s, and in 12%

of the tibiofibular trunks (Aerden 2014).