The presence of peripheral arterial disease (PAD) in patients with diabetes can result in devastating complications. Multidisciplinary care is critical for these patients. Accordingly, these authors review the current literature and offer pertinent diagnostic insights and keys to effective treatment.
With diabetes affecting 5 to 10 percent of the U.S. population, effective management of diabetes-related complications is imperative both socially and fiscally.
Foot ulcers develop in approximately 15 percent of patients with diabetes with an annual incidence of foot ulceration of slightly more than 2 percent among all people with diabetes and between 5 and 7.5 percent among people with diabetes and peripheral neuropathy.¹ Singh and colleagues have estimated that there is a 25 percent lifetime risk for someone with diabetes to develop a foot ulceration during his or her lifetime.²
Foot ulcers are a harbinger of amputation and they precede 85 percent of lower limb amputations.³This statistic highlights the importance of ulcer prevention and appropriate management of foot ulcers that are already present.
There are a number of contributing factors that interact and as they aggregate, they may lead to a foot ulceration.⁴ Reiber and colleagues established a causal pathway to foot ulceration in people with diabetes. Based on an analysis of 146 patients with foot ulcers, these researchers found that the triad of peripheral neuropathy, trauma and deformity were present in almost two-thirds of the patients with foot ulcers.⁵
However, this study occurred in an outpatient diabetic foot clinic and may have excluded those patients admitted to the hospital or those with limb ischemia requiring surgical intervention. Therefore, the study may have underestimated the level of infection and peripheral arterial disease (PAD) that others have reported.⁶

The prevalence of PAD in people with diabetic foot ulcers ranges wildly from 10 to 60 percent.⁶ This large variation may be the result of using different criteria for defining PAD among different centers.

A Closer Look At The Literature On PAD

The European Study Group on Diabetes and the Lower Extremity (Eurodiale), which is a collaborative network of 14 European centers, conducted a large multicenter study to obtain data on clinical outcomes in patients presenting with a foot ulcer.⁷ This multidisciplinary group initiated a prospective data collection study for 1,229 consecutive patients presenting with a new foot ulcer. Peripheral arterial disease was present in 49 percent of patients but the incidence varied from 22 to 73 percent among the different participating centers.
This variation may be related to the differences in the prevalence of PAD but it more likely highlights the differences in the criteria used to define PAD. In patients without diabetes, the ankle brachial index (ABI) is the method of choice to screen for PAD. However, given the reduced compliance of blood vessels in diabetes secondary to arterial calcification, the pressures may not be accurate and the results may be misleading.
The researchers also found that the presence of PAD is a strong predictor of a non-healing foot ulcer.⁷ In addition, patients with diabetes had more severe disease in the distal arteries in comparison to those without diabetes. The study also found a relatively high prevalence of infection with 58 percent of all ulcers infected at initial presentation.
Previous studies have demonstrated that the combination of infection and PAD results in the worst outcome. Armstrong and colleagues noted that patients presenting with a combination of infection and ischemia were 90 times more likely to undergo amputation than those without infection and ischemia.⁸ Ischemia in extremities with open wounds prolongs or prevents healing, and is a risk factor for amputation. Peripheral vascular disease and impaired distal perfusion associated with diabetes affect the delivery of immune cells and antimicrobials to the target site. The metabolic demands of an infection may cause a limb with severe ischemia to develop local necrosis or gangrene.

Mastering The Crucial Diagnostic Elements

Peripheral arterial disease is a component cause that may lead to foot ulcerations and therefore is an important element of the history exam.1 Symptoms of PAD may include claudication, rest pain or a non-healing ulcer.

One should question all patients about ambulatory calf, thigh and buttock pain.⁴Exercise-induced muscular cramps can, indeed, occur with diabetes but patients infrequently complain because they often have a self-imposed limitation to sustained walking. It is worth noting that the neuropathic patient may not have classic claudication and instead may present with lower extremity fatigue upon exertion that relieves after rest. Important risk factors include hypertension, dyslipidemia and smoking.
Do not discount the importance of a thorough physical exam. One should palpate femoral, popliteal and pedal pulses on both limbs and note the quality. Weak or absent pulses point to occlusion, stenosis or calcification proximal to the abnormal findings.⁶ However, the presence of pedal pulses does not always indicate adequate circulation.

Andros and colleagues reported on a group of five patients with diabetes who had worsening gangrene or failed limited amputations, and palpable pedal pulses.⁹ The authors performed arteriography and noted occlusion of all three infrapopliteal arteries. Collateral blood flow may maintain a palpable pulse but may not offer enough blood flow to heal an ulcer. As a result, Andros and colleagues recommend performing arteriography if gangrene is present, irrespective of palpable pedal pulses.⁹ One may also evaluate arterial flow by Doppler and grade it as monophasic, biphasic or triphasic.
The American Diabetes Association recommends that all patients with diabetes over 50 have ABI measurements and that one perform this examination in younger patients with multiple PAD risk factors.⁴ Traditionally, the method of choice to screen for PAD has been the ABI. As previously noted, arterial non-compressibility may occur in as many as 40 percent of patients with diabetes, rendering the ABI findings spurious.
Arterial calcification will result in falsely elevated values and values greater than 1.3 are associated with an increased risk for amputation. An ABI value of less than 0.9 is considered indicative of PAD although this number is currently being reassessed. Values between 0.9 and 1.3 are generally considered normal. Values less than 0.5 indicate severe obstruction.
The toe brachial index (TBI) may be a better measure of peripheral pressure since the smaller vessels in the toes are generally spared from calcification. Low TBI values are generally associated with a greater risk of amputation.¹⁰
One can use the history, clinical exam and imaging to make the diagnosis. Patients presenting with intermittent claudication and/or rest pain should get referrals to a vascular surgeon. For those patients presenting with a non-healing wound, one must rule out infection and ischemia, and also ensure appropriate pressure reduction.
Physicians can assess the periwound perfusion and oxygenation levels with newer available technologies. A laser Doppler measures skin perfusion pressure (SPP), which may aid in predicting healing. Values greater than 30 mmHg are generally predictive of wound healing. Hyperspectral imaging can measure tissue oxygenation and deoxygenation, and is under current investigation as a healing predictor.
A thorough exam and the results of non-invasive vascular studies will help determine the need for a vascular surgery consultation. Obtain the exam and vascular studies early in the patient’s course so consultation is not needlessly delayed. A patient with a lower extremity wound and contributing peripheral ischemia should have a consult for vascular intervention. Although distal bypass is the “gold standard” for limb revascularization, an endovascular procedure may restore enough flow to the limb to allow the wound to heal, achieving the desired endpoint.

Salient Insights On PAD Treatment

The general principles of proper management of the diabetic foot ulcer include proper wound care, ensuring adequate limb perfusion, appropriate treatment of infection and initiation of a strict offloading plan.
One should aggressively debride infected wounds with prompt drainage of pus. Choose antibiotics based on suspected organisms. Appropriately obtained deep tissue cultures will help guide the antibiotic course. When there is extensive necrotic tissue with fluctuance and pus, as well as gas in the tissues visible on plain radiographs, emergent surgical debridement must take precedence. In these situations, the debridement trumps thoughts of reconstruction and must precede revascularization.
When one diagnoses limb ischemia, referral to a vascular surgeon is necessary to determine if the patient is a candidate for revascularization either by angioplasty or open bypass. Advances in distal lower extremity revascularization have revolutionized limb salvage and continue to be a necessary component in the overall treatment of ischemic ulcers.¹¹
The goal of any revascularization procedure is to restore pulsatile blood flow to the foot. The important occlusive lesions are generally present in the infrapopliteal arteries of the calf. In most cases, a successful bypass from the popliteal artery to an artery of the ankle or foot is possible, and will provide enough perfusion to heal a neuroischemic ulcer. Most often, the circulation is satisfactory to the popliteal artery, thereby making a long graft originating in the femoral artery unnecessary. Clinically, the presence of a good popliteal pulse and a non-palpable pedal pulse is a favorable finding for a distal pedal bypass.
When it comes to the patient with a great deal of ischemia and tibial artery occlusion, angioplasty generally does not establish adequate and durable circulation so a bypass is the preferred procedure in moderate to severe occlusive lesions. An autogenous vein from the leg or the arm will be durable as the five-year patency of a pedal bypass is comparable to a femoral to popliteal bypass. Pomposelli and colleagues reviewed outcomes in more than 1,000 patients who had a dorsalis pedis artery bypass. They found the bypass to be durable with a high likelihood of limb salvage.¹²

Most often, one can determine the choice of target artery for bypass by the quality of the recipient artery. The dorsalis pedis artery is the most common arterial “target” for distal bypass. However, if that artery is occluded and unavailable, the surgeon may use the posterior tibial or plantar arteries.
Although there are many factors to consider in choosing the target artery for revascularization, Neville and colleagues support consideration for revascularization of the artery directly feeding the ischemic angiosome.¹¹ In their retrospective analysis, Neville and colleagues reported higher rates of ulcer healing in ischemic wounds after direct revascularization bypass to a specific angiosome. However, if the only artery available does not provide direct flow to the affected angiosome, revascularization remains indicated as the increased pressures will result in increased perfusion to the ischemic area and assist in ulcer healing.

In Conclusion

The causative factors and effective practices to deal with the acute and chronic ulceration and gangrene are well known. However, the failure of limb salvage lies in our collective inability to implement a team approach to managing these difficult problems.
A multidisciplinary team, a group of highly trained specialists, is best suited to treat these conditions. The podiatric surgeon must work in close collaboration with the vascular surgeon. The neuroischemic foot ulcer is associated with increased morbidity and requires a specialized team. Collaboration between podiatric and vascular surgeons is emerging as the most effective alliance for achieving successful outcomes.
Dr. Bevilacqua is an Associate Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a Fellow of the American College of Foot and Ankle Surgeons.
Dr. Rogers is an Associate Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a Fellow of the American College of Foot and Ankle Orthopaedics and Medicine.
Dr. Andros is the Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a board certified vascular surgeon and is Co-Chairman of the Diabetic Foot Global Conference (DFCon).