Journal of Diabetes and Its Complications 30 (2016) 7–8

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Recognising peripheral arterial disease in diabetic patients: A step forward

Diabetes, a continuously growing pathology affecting more than 380 million persons worldwide, is a well-known independent predictor of symptomatic peripheral arterial disease (PAD) and major limb amputation (IDF Diabetes Atlas Group, 2013; Spiliopoulos, Katsanos, Karnabatidis, et al., 2010). Although in non-diabetic patients, asymptomatic or moderately symptomatic PAD (intermittent claudication), progresses slowly to eventually incite severe life-style limiting claudication and in 2%–3% of the cases critical limb ischemia (CLI; the last stage of PAD), this is not the case for diabetic patients (Norgren, Hiatt, Dormandy, et al., 2007). Atherosclerosis progression in patients suffering from diabetes is more rapid, whilst even minor foot trauma could result in non-healing ulceration, super-infection and limb loss, due to the combination of limb macroand/or microcirculatory compromise and peripheral neuropathy. Specifically, apart from ischemic disease, wound healing is further compromised by declined vasodilatory response attributed to an impairment of the nerve axon reflex that depends on healthy C-fibre nociceptor function causing local vasodilation in response to a painful stimulus. Autonomic dysfunction and denervation of dermal structures result in loss of skin integrity, favouring bacterial colonisation (Anonymous, 2006). Notably, decreased limb blood perfusion due to atherosclerotic arterial stenosis or occlusions, resulting in even medium-distance claudication, especially in elderly patients, is not sufficient to support wound healing, a process necessitating increased blood flow to the distal foot. Therefore, prompt diagnosis of a possible ischemic component in diabetic foot disease is extremely important in order to achieve rapid revascularization that will improve limb perfusion, facilitate wound healing, avoid amputation and prevent from amputation-associated morbidity and mortality. According to European Society for Vascular Surgery (ESVS) 2011 consensus document the identification of PAD should be based on an ABI b0.90, whereas CLI is defined by clinical and haemodynamic criteria as CLI, in both diabetic and non-diabetic patients, is defined as “persistently recurring ischemic rest pain requiring regular adequate analgesia for more than two weeks with an ankle systolic pressure 50 mmHg and/or toe systolic pressure 30 mmHg or ulceration or gangrene of the foot or toes, with an ankle systolic pressure 50 mmHg or toe systolic pressure 30 mmHg” (Setacci & Ricco, 2011). However, according to the same document, ankle systolic pressure should not be considered reliable parameter in diabetic patients with suspected CLI (level of evidence 2b; grade B), as Monckeberg medial calcific sclerosis resulting in partially compressible arteries produces falsely elevated pressure values, or in incompressible vessels obtaining no pressure result. Therefore, consen-

Conflicts of interest: None. http://dx.doi.org/10.1016/j.jdiacomp.2015.09.005 1056-8727/© 2016 Elsevier Inc. All rights reserved.

sus was that toe pressure measurement should be performed in diabetic patients considering that lack of compressibility is highly improbable in toe arteries. Nonetheless, level of evidence for this recommendation remains low (level 2b; grade B), as studies investigating TBI in diabetic patients are scarce (Setacci & Ricco, 2011). In their prospective, single centre, cross sectional, case–control study, Tehan et al. investigated the diagnostic accuracy of two widely used non-invasive lower limb vascular tests, ABI and toe brachial index (TBI), compared to continuous wave Doppler (CWD) ultrasound for the detection of PAD in diabetic versus non-diabetic patients (Tehan, Bray, & Chuter, 2016). In total 117 patients were enrolled. Colour duplex ultrasound (CFDU) was used to demonstrate the presence of PAD, which was defined as N 50% stenosis in at least one peripheral artery. CWD waveforms were blindly analysed and PAD positive patients were considered those demonstrating loss of normal multi-phasic CWD pattern. Abnormal ABI and TBI values were ≥ 0.90 to ≤ 1.4 and ≥0.70, respectively. Demographics were wellmatched between the two groups. CWD test resulted in the highest sensitivity and specificity (74.19% and 92.86%, respectively for diabetic patients; 84.21% and 96.3% respectively for non-diabetic patients) followed by TBI, whilst ABI demonstrated poor sensitivity in diabetic patients, as expected due to increased false negative results. Generally, all three tests had decreased sensitivity in detecting PAD in diabetic compared to non-diabetic patients. Nonetheless, specificity was similar between ABI and CWD (92.6% versus 92.8%, respectively) for diabetic patients and slightly inferior for non-diabetic patients (92.6% versus 96.3%), whilst TBI demonstrated inferior specificity rates compared to the other two tests both for diabetic (82.05%) and non-diabetic (74.07%) population. Moreover, ROC analysis detected superior clinical efficacy for TBI compared to ABI in diabetic patients. Interestingly, mean ABI and TBI values were not significantly different between diabetic and non-diabetic groups. These results indicate that this simple non-invasive diagnostic test could detect more accurately PAD in the diabetic population. A drawback of CWD assessment is the fact that as for CFDU, it should be performed and interpreted by specifically trained staff, compared to ABI and TBI tests that can be easily performed by the majority of health-related professionals and do not require interpretation. Limitations of this study include the fact that PAD diagnosis was based on CFDU, which is not the gold standard for PAD diagnosis, especially for below the knee arterial disease. On the other hand, high inter-tester reliability of the CFDU scans was noted, whilst most of the patients suffered from infrapopliteal occlusions and therefore false CFDU results should be very limited. Furthermore, post-hoc categorisation of the two groups may have limited outcome generalizability. Nonetheless, abovementioned results are based on a well-designed

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Editorial / Journal of Diabetes and Its Complications 30 (2016) 7–8

and conducted prospective protocol investigating a relatively large patient sample, providing satisfactory study internal validity. Conclusively, outcomes of Tehan et al. indicate that CWD is more sensitive in detecting PAD both in diabetic and non-diabetic patients compared to ABI or TBI. Further larger-scale research is mandatory in order to provide high level of evidence data and endorse CWD as standard test in everyday clinical practice, especially for patients suffering from diabetes in which early diagnosis and treatment are of the outmost importance. Notably, novel methods providing functional information on tissue microvascular perfusion and skin viability, such as forefoot transcutaneous oxygen measurement (TCPO2) and skin perfusion pressure (SPP), should be made widely available amongst diabetic foot specialists. This would further improve clinical assessment of diabetic foot by providing direct measurements of limb tissue perfusion compared to indirect hemodynamic information obtained by ABI, TBI, CWD and CFDU and could be utilised for the diagnosis, post-procedural follow up and prognosis of diabetic PAD patients.

References Evidence-based protocol for diabetic foot ulcers. Plastic and Reconstructive Surgery, 117(7S)(2006). 193S–209S.

IDF Diabetes Atlas Group (2013). Update of mortality attributable to diabetes for the IDF Diabetes Atlas: Estimates for the year. Diabetes Research and Clinical Practice, 100(2), 277–279. Norgren, L., Hiatt, W. R., Dormandy, J. A., Nehler, M. R., Harris, K. A., Fowkes, F. G., ... Rosenfield, K. (2007). TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). European Journal of Vascular and Endovascular Surgery, 33(Suppl. 1), S1–S75. Setacci, C., & Ricco, J. B. (2011). European Society for Vascular Surgery. Guidelines for critical limb ischaemia and diabetic foot—introduction. European Journal of Vascular and Endovascular Surgery, 42(Suppl. 2), S1–S3. Spiliopoulos, S., Katsanos, K., Karnabatidis, D., Diamantopoulos, A, Kagadis, G. C., Christeas, N, ... Rosenfield, K. (2010). Cryoplasty versus conventional balloon angioplasty of the femoropopliteal artery in diabetic patients: Long-term results from a prospective randomized single-center controlled trial. Cardiovascular and Interventional Radiology, 33(5), 929–938. Tehan, P. E., Bray, A., & Chuter, V. H. (2016). Non-invasive vascular assessment in the foot with diabetes: Sensitivity and specificity of the ankle brachial index, toe brachial index and continuous wave Doppler in detecting peripheral arterial disease. The Journal of Diabetic Complications, 30, 155–160.

Stavros Spiliopoulos Department of Interventional Radiology, Patras University Hospital 26500, Rio, Greece Tel.: +30 2613603218(Secr)

Recognising peripheral arterial disease in diabetic patients: A step forward.

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