8 Clinical Features and Diagnosis of Macrovascular Disease

of Macrovascular Disease

Chantel Hile, MD , Nikhil Kansal, MD , Allen Hamdan, MD , and Frank W. LoGerfo, MD

INTRODUCTION

Atherosclerotic peripheral vascular disease in patients with diabetes is a major factor in the progression of diabetic foot pathology. The rate of lower extremity amputation in the diabetic population is 15 times that seen in the nondiabetic population (1). A number of factors conspire in the patient with diabetes, each of which synergistically contributes to this extremely high amputation rate. Peripheral neuropathy, infection, microvascular changes, and macrovascular changes all have complex interplay. Peripheral neuropathy leads to structural and sensory changes within the foot, making the limb injury-prone. In addition, once it occurs, that injury is often not easily detectable and heals slowly if at all. Microvascular changes are nonocclusive changes in the microcirculation that lead to impairment of normal cellular exchange, again preventing easy healing. Infection in patients with diabetes can often be aggressive and polymicrobial. Macrovascular disease, atherosclerosis of the peripheral arteries, contributes to poor perfusion of the extremities.

Although the underlying pathogenesis of atherosclerotic disease in patients with diabetes is similar to that noted in patients without diabetes, there are some significant differences.

It is important to realize that the diabetic foot is more susceptible to moderate changes in perfusion than the nondiabetic foot, resulting in a greater sensitivity to atherosclerotic occlusive disease. Compounding this scenario is the fact that patients with diabetes are noted to have a fourfold increase in the prevalence of atherosclerosis as well as a propen- sity for accelerated atherosclerosis. This chapter will review the pathobiology and anatomic distribution of occlusive disease in the patient with diabetes, the usual clinical presentation of peripheral vascular disease, and the various diagnostic modalities useful in planning treatment. It will conclude with a diagnostic and treatment protocol that can be used in patients presenting with this multifactorial disease process.

PATHOLOGY OF ATHEROSCLEROSIS IN DIABETES

Understanding of the basic pathology of atherosclerosis in patients with diabetes has evolved considerably over the last 15 years. One fundamental concept that has been dis- proved is the commonly held belief that patients with diabetes are prone to “small vessel disease.” This popular misconception, in which the arterioles of the ankle and foot are

From: The Diabetic Foot, Second Edition

Edited by: A. Veves, J. M. Giurini, and F. W. LoGerfo © Humana Press Inc., Totowa, NJ

147

thought to be preferentially affected by atherosclerotic occlusive disease, originated from a paper by Goldenberg (2). In his retrospective review of amputation specimens from patients with and without diabetes, Goldenberg used periodic acid-Schiff staining to histologically examine the peripheral vasculature. Deposits that stained positive in the arterioles of the foot and ankle were noted to be unique to the diabetic specimens. These deposits were interpreted as being atherosclerotic lesions and were felt to be the principle cause of the poor outcome seen in patients with diabetes. The prevailing belief became that patients with diabetes were not candidates for distal revascularization because the “small vessels” (arte- rioles) were somehow preferentially involved in the occlusive process.

Further work in an attempt to categorize and quantify whether there was a diffuse and unique type of atherosclerosis between patients with and without diabetes was evaluated by a number of research studies. In a prospective analysis of amputation specimens, this time with blinded histological review, Strandness and coworkers (3) used periodic acid- Schiff staining and showed that there was no difference in the atherosclerotic pattern between patients with and without diabetes. Both groups were noted to have a paucity of occlusive disease at the arteriolar level. In another prospective study, using a sophisticated casting technique for evaluating the peripheral vasculature, Conrad (4) confirmed the sim- ilar characteristics of arteriolar atherosclerosis in both groups of patients. To dispel the theory that the peripheral vascular bed in patients with diabetes was less “reactive,”

Barner (5) measured the flow rate in femoropopliteal bypass grafts in the two groups.

By infusing papavarine into the outflow vascular bed, he was able to assess any differ- ence in vessel reactivity; again, no difference was noted between patients with and without diabetes. It is clear from these studies that a unique “small vessel” occlusive pattern does not exist in patients with diabetes. The label of “unreconstructable disease”

has led to many unnecessary amputations in the diabetic population.

There are, however, some aspects of atherosclerotic peripheral vascular disease, which are different from that noted in the nondiabetic population. As has already been mentioned, patients with diabetes have a fourfold higher prevalence of atherosclerosis and this occlusive disease is known to progress at a more rapid rate. It is also notewor- thy that diabetic patients with the sequelae of atherosclerotic disease often present at an earlier age than their counterparts without diabetes. In addition, patients with diabetes often have a unique distribution of atherosclerosis at the arterial level. Unlike in their counterparts without diabetes, occlusive disease in patients with diabetes has a distinct propensity to occur in the infrageniculate vessels in the calf. The affected arteries, namely the anterior tibial artery, posterior tibial artery, and peroneal artery, are more severely affected and are more likely to present with occlusion in patients with diabetes (Figs. 1 and 2). Although these arteries are preferentially affected, the proximal arter- ies to the level of the popliteal artery are often spared in patients with diabetes. Equally important is the observation that the arteries of the foot, namely the dorsalis pedis artery, are commonly spared from the occlusive disease (Fig. 3). These patterns are general- izations, and it is important to mention that some patients with diabetes present with atherosclerotic lesions very similar to those seen in patients without diabetes.

These observations have had a crucial impact in the way that peripheral vascular

disease in patients with diabetes is approached. Based in part on the expected presence

of the so-called small vessel disease, in the past, patients with diabetes were not treated

as aggressively as they are currently. Because patients with diabetes were thought to have occlusive disease at the arteriolar level, bypass to patent vessels proximal to the foot was thought to be futile. Now, as our understanding of the disease process has evolved, so has our treatment protocol. Understanding that, in patients with diabetes, calf vessels are more severely affected by atherosclerosis whereas the pedal vessels are spared, we have been able to modify our approach to the evaluation and treatment of patients with diabetes. A more aggressive approach to identifying pedal arteries suit- able for bypass along with aggressive measures to control local infection has radically changed the prognosis of peripheral vascular disease in the diabetic foot.

Fig. 1. This digital subtraction angiogram shows the below-knee popliteal artery and tibial

arteries in a patient with diabetes. The diffuse pattern of atherosclerotic disease is typical of the

type seen in this population.

CLINICAL PRESENTATION

In order to appreciate the differences in the presentation of peripheral vascular disease in patients with diabetes, it is important to understand its presentation in patients with- out diabetes. Atherosclerotic disease is manifest by a continuum of signs and symptoms that can be divided into categories. These categories in order of increasing severity are:

claudication, rest pain, and tissue loss. These categories represent the normal evolution of symptoms in the nondiabetic population with peripheral vascular disease. Because of the effects of diabetic neuropathy, this progression of symptoms may be absent in patients with diabetes. This topic is further detailed in another chapter.

Claudication is defined as ischemic muscle pain resulting from inadequate blood flow.

This lack of tissue perfusion is owing to proximal arterial occlusive disease resulting in

Fig. 2. This is a more distal film of the same patient in Fig. 1. It is evident that there are no

patent tibial arteries. The blood flow to the foot in this patient is entirely dependent on the small

collateral vessels that are seen. In the past, with this angiogram, this patient would not have been

considered a candidate for bypass. Now, however, it is known that the pedal arteries in diabetic

patients with this type of disease must be visualized. Many of these patients are found to have

pedal arteries amenable to bypass procedures (see Figs. 3, 6, and 7).

diminished blood flow to large muscle groups. For example, claudication of the thigh and buttocks is a result of occlusive disease of the aortoiliac system, whereas claudication of the calf results from superficial femoral artery occlusion. Calf claudication is a common initial presenting symptom. The pain is characteristic, involving the calf muscles, and is usually described as “cramping” in nature. It is often aggravated by exercise, and relieved by sev- eral minutes of rest. Often helpful in tracking the progression of claudication is the patient’s ability to quantify the amount of distance they are able to walk before becoming sympto- matic. This distance is noted as the “initial claudication distance.” This assessment is extremely valuable in clinical practice for the follow-up of patients with peripheral vascular disease. As a result of the rich collateral network of blood supply to the lower extremity, occlusive disease at two levels is usually required to cause claudication. This does not hold true for patients with diabetes, however, because they are more susceptible than nondiabet- ics to small changes in tissue perfusion. Therefore, it is not uncommon for patients with dia- betes to present with symptoms resulting from vascular occlusive disease localized to one level, whereas nondiabetics will often have multilevel disease by the time they become symptomatic. Claudication is an important early sign of peripheral vascular disease, which should always be elicited in a patient’s history. Careful follow-up and monitoring of claudi- cation can identify patients with worsening occlusive disease before the progression to more severe pathology. Most patients, about 75%, will remain stable regarding their claudication, i.e., the distance they can walk does not lessen over time. Of patients with diabetes with claudication, operative treatment or amputations are required in only 1% of patients per year.

Fig. 3. This is a lateral view of the foot (nonsubtraction) of a diabetic patient with severe

tibial artery occlusive disease. This patient had no patent tibial vessels to which bypass could

be performed. Note the location and patency of the artery on the dorsum of the foot. This is

the dorsalis pedis artery and is an excellent target artery for bypass.

Rest pain is another symptom of peripheral vascular disease and is an indication of severe occlusive disease. It is characterized as a “burning pain” involving either the forefoot or the region of the metatarsal heads. Unlike claudication, rest pain is constant, occurs even at rest (most commonly at night with leg elevation), and is relieved only by dependent hanging of the extremity. Patients will often dangle the affected leg off the side of the bed at night in order to gain relief. Rest pain is often an ominous sign of severely progressive occlusive disease. Unfortunately, secondary to peripheral neuropathy, diabetics may not develop rest pain, or it may be confused with the pain of neuropathy.

The absence of this hallmark clinical sign may lead to a delay in the diagnosis of severe ischemia of the foot.

Tissue loss is the most severe presentation of vascular disease, and can be broken-down into two separate types: foot ulceration and gangrene. Ulceration is the most common presentation of peripheral vascular disease in patients with diabetes. The increased inci- dence of foot ulceration in diabetics is resulting from the synergistic effects of the various other contributing factors as discussed early in this chapter. It is important to realize that ulceration in patients with diabetes is rarely owing to ischemia alone; a fact that should be kept in mind when devising treatment strategy. All patients with diabetes presenting with foot ulceration should be evaluated for peripheral vascular disease. Gangrene seen in patients with and without diabetes is quite similar. The gangrenous extremity is a hallmark of severe vascular occlusive disease. The diagnosis is established at clinical exam. The affected extremity appears black and shriveled, is insensate, and has no motor function.

Gangrene as defined does not include the presence of infection, and as such, is of little systemic consequence in the affected patient. This is not the case when the gangrenous tis- sue is secondarily infected, or the so-called wet gangrene. This separate clinical entity is characterized by the classical findings of gangrene, with the addition of signs of invasive infection: fever, chills, leukocytosis, erythema, cellulitis, pus, abscess, or osteomyelitis. In contrast to uninfected or “dry gangrene,” wet gangrene poses a surgical emergency.

Any discussion regarding the presentation of peripheral vascular disease would not be complete without the mention of infection as a presenting symptom. Although less com- mon in the nondiabetic population, infection can be the first sign of peripheral ischemia in patients with diabetes. In addition, infection associated with ulceration and gangrene is also more common in patients with diabetes. These infections are often aggressive, polymicrobial, cause significant tissue destruction, and are the most common cause of amputation in the diabetic foot. In terms of presentation, it is crucial to realize that the signs of infection may be subtle. Because the normal immune response to infection is altered in patients with diabetes, patients with massive invasive infection may not mani- fest with classic signs such as fever, chills, leukocytosis, or even cellulitis. In fact, many diabetic patients with foot infection may present merely with hyperglycemia, or simply an increase in their insulin requirement. It is because of these factors that the index of suspi- cion for foot infection in patients with diabetes should always be high.

DIAGNOSIS AND EVALUATION

The cornerstone in the evaluation of patients with diabetes and peripheral vascular

disease remains the physical exam. Our experience has shown that the absence of pedal

pulses, either dorsalis pedis or posterior tibial, is an indication of advanced occlusive

disease. Palpation of the peripheral pulses should include the femoral, popliteal, and pedal vessels. Although this is a skill that takes time to develop, when an examination is performed by an experienced person, absence of both pedal pulses is a clear marker of vascular disease. Beyond physical exam there is a myriad of noninvasive and invasive diagnostic modalities available to the clinician. Noninvasive modalities are preferred for screening and initial workup and include ankle–brachial indices, pulse volume recordings (PVR), segmental pressures, toe pressures, and transcutaneous oxygen measurements.

There are many conflicting arguments regarding the efficacy and reproducibility of these methods. The continued controversy, along with the inapplicability of many of these tests in patients with diabetes, has hampered their usefulness. Magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) are two relatively noninvasive tests, yet are being considered as alternatives to the more invasive digital subtraction angiography. They have significant limitations, and have yet to be accepted as replacements of conventional angiography. The only invasive diagnostic test in the evaluation of vascular disease is digital subtraction angiography. This is currently con- sidered the “gold standard” in the assessment of occlusive disease.

Noninvasive measurements in patients with peripheral vascular disease can often yield a large amount of information regarding the location and severity of occlusive lesions. Unfortunately, many of these modalities are either altered by the diabetic process, or simply cannot be performed consistently on the diabetic foot.

Ankle–brachial index is an easily measurable way to compare the systolic pressure of the upper extremity to that of the affected lower extremity. Using a Doppler probe and a blood pressure cuff, the systolic pressure in the pedal arteries (dorsalis pedis or posterior tibial) is taken. The higher of these two measurements is compared with a similarly taken brachial artery systolic pressure (again, the highest brachial pressure is used). A ratio (ankle–brachial) of less than 1 is considered a sign of impaired flow to the extremity (Table 1). Because of the arterial wall medial calcification that occurs in patients with diabetes, the arteries are often less compressible than similar arteries at the same pressure. As a result, this measurement is often falsely elevated and unre- liable. In some patients with diabetes, this process is so severe that the cuff pressure cannot occlude the arteries; these vessels are referred to as “noncompressible.” It is for this reason that this measurement can have limited clinical applicability in patients with diabetes. Nevertheless, the ADA Consensus Statement recommends a screening ABI be done on all patients with diabetes over 50 years of age and, if normal, repeated every 5 years. Those diabetic patients with risk factors for peripheral arte- rial disease should be screened with an ABI no matter the age (6).

Table 1

Diagnostic Criteria for Peripheral Arterial Disease Based on Ankle–Brachial Index Measurements

0.91–1.30 Normal

0.70–0.90 Mild obstruction

0.40–0.69 Moderate obstruction

<0.40 Severe obstruction

The technique of measuring segmental pressures from the high thigh down to the foot is a popular method for assessing the location of occlusive lesions. This test is per- formed by placing a series of pressure cuffs at various levels along the affected extremity.

The systolic pressure measurements at each level are an indication of the amount of tissue perfusion at that level. A drop in the pressure from one level to the next is predictive of an occlusive lesion within the arterial system between those two levels (Figs. 4 and 5).

Unfortunately, this measurement is also affected by the arterial wall calcification in patients with diabetes, and as a result is often not reliable in this population.

Fig. 4. This is an example of a pulse-volume recording (PVR) data sheet. Included are the

segmental pressures (along-side the diagram) and the ankle–brachial indices (ABIs; bottom of

diagram). This patient is diabetic and was noted to have elevated segmental pressures (the

absolute pressure increases distally) and elevated ABIs (both ABIs are greater than 1). Because

medial wall calcification often causes elevation of these two measurements, PVRs are utilized to

assess the presence or absence of true occlusive disease. Note that the amplitude of the wave-

forms is maintained from the thigh to the metatarsal level. This indicates that this patient does

not have significant vascular occlusive disease.

As it became increasingly evident that the vasculature of the foot was spared the changes noted in the more proximal vessels of the calf, measurement of digital toe pressures was initiated. Subsequent study has confirmed that toe pressures are not hampered by the coex- istence of diabetes. In fact, Vincent and Towne (7) showed that toe pressure was an “accu- rate hemodynamic indicator of total peripheral arterial obstructive disease” in patients with diabetes. Generally, a toe pressure less than 40 mmHg predicts healing difficulties.

Although this methodology can be a useful adjunct in the evaluation of vascular disease in

Fig. 5. This PVR recording is also taken from a patient with diabetes. As in Fig. 6, this

patient is noted to have elevated segmental pressures and ABIs. The difference is that this

patient clearly has “dampening” of the waveforms on both extremities beginning at the level

of the ankle. This decrease in amplitude of the tracing suggests that an occlusive vascular

lesion exists between the level of the calf and ankle. As you can see, the results of this test

are merely qualitative, and do not provide an objective quantification of the extent of vascu-

lar disease present.

the diabetic foot, its use is often obviated by the presence of ulceration, gangrene, or ampu- tation of the toe, and unfamiliarity with its use at some hospitals.

PVR are an assessment of the flow characteristics within the arterial system. A series of air plethysmography cuffs are placed at the toe, ankle, calf, low thigh, and high thigh.

These cuffs detect the small change in diameter of the leg during systole and diastole. This change with each heartbeat is recorded as a waveform (Figs. 4 and 5). A progression from

“triphasic” to “monophasic” or “dampened waveform” would be indicative of occlusive disease and a waveform less than 4 at the toe level indicate an extent of ischemia such that tissue healing is unlikely. The advantage of this method is the fact that it is not hampered by arterial wall calcification (Fig. 5). For patients with a normal ABI but clear claudica- tion symptoms, a reasonable option is the treadmill functional test. Patients whose symp- toms truly are because of claudication will have a higher than 20 mmHg drop in ankle pressure after a period of exercise. Although PVR testing does confer some information, it is mostly a qualitative rather than quantitative examination, and is difficult to use as an absolute or objective reference regarding the severity of the disease.

Transcutaneous oxygen measurements are used to evaluate the amount of tissue perfu- sion in patients with vascular disease. This method had been used to predict the healing potential of a diseased extremity, i.e., to determine if the patient would be able to heal a wound that either exists, or would be created by performing a surgical procedure. The test is performed by placing a probe over the metatarsal region of the affected foot. After equil- ibrating to a specific temperature, the oxygen level is determined. Enthusiasm for this meas- urement has been hampered by the large degree of variability noted in the measurements.

Many different factors, including the site of measurement and the temperature, affect the oxygen reading; but in a review of multiple factors, no one factor could account for the vari- ability (8). Another review noted that the transcutaneous oxygen tension (TcPO2) was lower in diabetics than nondiabetics when comparing groups with similar disease severity (9).

Although there is some literature supporting the use of TcPO2 in the evaluation of the diabetic foot (10), results are difficult to interpret. This has led to a “gray-zone” of values without a significantly predictive scale. Rule of thumb is that a value of less than 30 mmHg is associated with poor healing. The continued evaluation of this modality may lead to a better understanding of its importance.

The “gold standard” in the evaluation of diabetic patients with peripheral vascular disease is digital subtraction angiography. The results of conventional angiography have been greatly enhanced with the advent of digital subtraction technology (Figs. 3 and 6).

This technology, by subtracting away the bone and soft tissue to better visualize the contrast

column, allows the radiographer to follow the contrast bolus over a greater period of

time and allows for selection of the optimal images. This has resulted in greater visua-

lization of the distal and pedal vessels. The most important aspect for a radiographer to

understand, especially in patients with diabetes, is that even in the presence of tibial ves-

sel occlusion, priority must be given to visualizing the pedal anatomy. Angiograms are

often terminated prematurely in these situations with the misconception that tibial

occlusion represents “unreconstructable disease.” Two views (anteroposterior and lat-

eral) of the foot should be obtained and care should be taken to avoid excessive plantar

flexion of the foot during the exam as this may impede flow to the dorsalis pedis artery

(Fig. 7). The prevailing concern with the use of angiography is the risk of renal failure

in diabetic patients with preexisting renal insufficiency. The most important factor in the

Fig. 6. This is the same patient seen in Fig. 3 viewed using digital subtraction technology.

This technology allows improved visualization of difficult to see arteries, especially in situations in which blood flow is diminished.

Fig. 7. This is an AP view of the foot of the patient seen in Figs. 3 and 6. The widely patent

dorsalis pedis artery is well visualized and can be seen feeding the pedal arch. It is mandatory to

obtain a lateral and AP view angiogram of the foot when evaluating the pedal vasculature.

prevention of renal failure in these patients has been the use of hydration prior to obtain- ing the angiogram (11). When renal failure does occur, it is almost always reversible (12), but may delay the arterial reconstructive surgery for several days while the creati- nine returns to baseline. Recent data suggest that sodium bicarbonate infusion prior to contrast exposure may be even more effective than normal saline hydration (13) and N- acetylcysteine treatment preceding and following contrast exposure has also been shown to help prevent contrast nephropathy (14).

MRA and spiral CTA have been investigated as alternatives to conventional angio- graphy. The ability of MRA to provide information without the risks related to catheter- ization, nephrotoxicity and radiation exposure makes it an attractive option. MRA using

“2D time of flight” was used to assess the distal lower extremity vasculature in diabetics in comparison to digital subtraction angiography (15). Although MRA was shown to have acceptable sensitivity and specificity in the evaluation of the tibial vessels, it was not ideal for identifying patent pedal vessels. The three areas that are prone to error by MRA are as follow:

1. The bifurcation of the peroneal artery;

2. The plantar arch; and

3. Retrograde flow into the lateral plantar artery.

These shortcomings are especially significant in the diabetic population in whom the pedal vessels are often a target of revascularization. Weighing the pluses and minuses of this study, the American Diabetes Association endorsed its use with the caveat that X-ray angiography remains the gold standard for vascular imaging (6).

The role of CTA in the evaluation of peripheral vascular disease has also been inves- tigated. Some reviews (16) have reported an accuracy of 95%. Confounding items such as overlapping leg veins and vessel wall calcification can contribute to inaccurate CTA readings. This modality is also limited by the amount of contrast required to image the entire length from the distal aorta to the foot. For this reason, studies evaluating CTA have not included the pedal vessels in their evaluation, and to do so would likely require prohibitively high contrast levels. The combination of inaccuracy with calcification and the inability to visualize the pedal vessels makes CTA an ineffective means of evaluat- ing vascular disease in the diabetic.

Overall, noninvasive diagnostic tests are quite useful in the evaluation of nondiabetic patients with peripheral vascular disease. Unfortunately, these tests are easy to misin- terpret in patients with diabetes. The combination of peripheral neuropathy and medial arterial wall calcification limits the ability to accurately diagnose and predict the loca- tion or severity of occlusive disease by noninvasive methods. Because the traditional approach to the work-up of peripheral vascular disease is not adequate in the patient with diabetes, a separate algorithm in the management of these patients is required.

TREATMENT PROTOCOL

The approach to the diabetic patient with signs and symptoms of vascular occlusive

disease is separate from that utilized in the nondiabetic population. Patients being evalu-

ated with diabetic foot complications should be considered at high risk both for the

development and progression of atherosclerotic occlusive disease. In lieu of the previ-

ously discussed shortcomings of noninvasive testing, we place emphasis on the presence

or absence of pedal pulses (Fig. 8). As a general rule, if a patient has a diabetic foot ulcer and nonpalpable pulses, he or she is regarded as having a significant component of ischemia. If the ulcer does not heal with conservative measures or if bone, joint, or ten- don is involved, digital subtraction arteriography should be performed.

The management of a patient that presents with an ischemic diabetic foot should be approached in a premeditated and stepwise fashion. The initial priority is the prompt and thorough drainage and/or debridement of any infected or necrotic tissue. This may be accomplished by simple incision and debridement of an abscess, or may require more extensive procedures. The goal of these procedures, whether extensive soft tissue debridement or partial amputation is the final result, is the complete eradication of an ongoing source of sepsis. Multiple trips to the operating suite may be needed to insure adequate results. Again, one must keep in mind that the signs of continued infection in diabetics can be blunted and their diagnosis requires a high level of suspicion. Once the infection is controlled, the next step is determining the level of ischemia. This step should not be delayed, and can be pursued even in the presence of active infection. As was previously mentioned, the absence of pedal pulses is a good predictor of the need for angiography, especially in the setting of tissue loss, poor healing, or gangrene. Once angiography is complete, planning for revascularization is undertaken. Even in the face of tibial and peroneal occlusion, the pedal vessels should be evaluated for patency. The fundamental goal of any revascularization in the diabetic foot should be restoration of pulsatile blood flow to the foot. The priority of bypass vessels should be to those arteries with direct runoff into the foot (anterior and posterior tibial arteries), however; results of bypass to the peroneal artery are also excellent. Once revascularization has been accomplished, attention can then again be turned to the repair of the initial foot lesion.

Secondary revision or closure may be required, and may be carried out as a separate procedure.

The care and management of the patient with diabetes presenting with the sequelae

of peripheral vascular disease is a complex undertaking. A thorough knowledge of the

pathobiology associated with this disease is essential. All aspects of the care of these

Fig. 8. Algorithm for assessing peripheral vascular disease in the patient with diabetes (based

on recommendations laid out in the 2003 ADA Consensus Statement [6]).

patients, from presentation to diagnosis to treatment, must be tailored to patients with diabetes. As the evolution of our understanding of this disease process has evolved, so has our ability to effect improvement in outcome. Patients presenting with diabetic foot complications exacerbated by atherosclerotic occlusive disease are now treated very aggressively. The use of distal bypass grafting in appropriate patients has led to improved results and an optimistic prognosis for the diabetic population.

REFERENCES

1. Armstrong DG, Lavery LA. Diabetic foot ulcers: prevention, diagnosis and classification.

Am Fam Phys 1998;57(6):1325–1332.

2. Goldenberg SG, Alex M, Joshi RA, et al. Nonatheromatous peripheral vascular disease of the lower extremity in diabetes mellitus. Diabetes 1959;8:261–273.

3. Strandness DE, Priest RE, Gibbons GE. Combined clinical and pathologic study of diabetic and nondiabetic peripheral arterial disease. Diabetes 1964;13:366–372.

4. Conrad MC. Large and small artery occlusion in diabetics and nondiabetics with severe vascular disease. Circulation 1967;36:83–91.

5. Barner HB, Kaiser GC, Willman VL. Blood flow in the diabetic leg. Circulation 1971;43:

391–394.

6. Peripheral Arterial Disease in People with Diabetes, American Diabetes Association Consensus Statement. Diabetes Care, 2003;26(12):3333–3341.

7. Vincent DG, Salles-Cunha SX, Bernhard VM, Taine JB. Noninvasive assessment of toe sys- tolic pressures with special reference to diabetes mellitus. J Cardiovasc Surg 1983;24(1):22–28.

8. Boyko EJ, Afroni JF. Predictors of transcutaneous oxygen tension in the lower limbs of diabetic subjects. Diabet Med 1996;13:549–554.

9. Rooke TW, Osmundson PJ. The influence of age, sex, smoking, and diabetes on lower limb transcutaneois oxygen tension in patients with arterial occlusive disease. Arch Intern Med 1990;150:129–132.

10. Eke CC, Bunt TJ, Killeen JD. A prospective evaluation of transcutaaneois oxygen measure- ments in the management of diabetic foot problems. J Vasc Surg 1995;22(4):485–490.

11. Solomon R, Werner C, et al. Effects of saline, mannitol, and furosemide on acute decreases in renal function by radiocontrast agents. N Engl J Med 1994;331:1416–1420.

12. Parfrey PS, Griffiths SM, Barret BJ, et al. Contrast material-induced renal failure in patients with diabets mellitus, renal insufficiency, or both: a prospective controlled study. N Engl J Med 1989;320:143.

13. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate. JAMA 2004;291(19):2328–2334.14. Birck R, Krzossk S, et al.

Acetylcysteine for prevention of contrast nephropathy: meta-analysis, Lancet 2003;362:598–603.

15. McDermott VG, Meakem TJ, Carpenter JP, et al. Magnetic resonance angiography of the distal lower extremity. Clin Radiol 1995;50(11):747–746.

16. Lawrence JA, Kim D, Kent KC, et al. Lower extremity spiral CT angiography versus catheter angiograhy. Radiology 1995;194(3):903–908.

SUGGESTED READING

1. Kannel WB, McGee DL. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes Care 1979;2:120–126.

2. Boulton A, Buckenham T, et al. Report of the Diabetic Foot and Amputation Group.

Diabetes Med 1995;13(9 Suppl 4):S27–S42.

Chirurgae et Gynaecologiae 1992;81(2):122–124.

4. LoGerfo FW, Gibbons GW, Pomposelli FB, et al. Trends in the care of the diabetic foot.

Arch Surg 1992;127(5):617–620.

5. Gils CC, Wheeler LA, Mellstrom M, et al. Amputation prevention by vascular surgery and podiatry collaboration in high-risk diabetic and nondiabetic patients. Diabetes Care 1999;22(5):678–683.

6. LoGerfo FW, Gibbons GW. Vascular disease of the lower extremities in diabetes mellitus.

Endocrinol Metab Clin N Am 1996;25(2):439–445.

7. Chang BB, Shah DM, Darling RC 3rd, Leather RP. Treatment of the diabetic foot from a vascular surgeon’s viewpoint. Clin Orthop Rel Res 1993;296:27–30.

8. Estes JM, Pomposelli FB. Lower extremity arterial reconstruction in patients with diabetes mellitus. Diabetes Med 1996;S43–S46.

9. Akbari CM, LoGerfo FW. Diabetes and peripheral vascular disease. J Vasc Surg 1999;30(2):

373–384.

10. Bunt TJ, Holloway GA. TcPO2 as an accurate predictor of therapy in limb salvage. Ann Vasc Surg 1996;10:224–227.

11. Stevens MJ, Goss DE, Foster AV, et al. Abnormal digital pressure measurements in diabetic neuropathic foot ulceration. Diabetes Med 1993;10(10):909–915.

12. Ramsey DE, Manke DA, SumnerDS. Toe blood pressure. A valuable adjunct to ankle pres- sure measurement for assessing peripheral arterial disease. J Cardiovasc Surg 1983;24(1):

43–48.

13. Carter SA, Tate RB. Value of toe pulse waves in addition to systolic pressures in the assess- ment of the severity of peripheral arterial disease and critical limb ischemia. J Vasc Surg 1996;24(2):258–265.

14. Ekelund L, Sjoqvist L, Thomas KA, Asberg B. MR angiography of abdominal and periph- eral arteries. Techniques and clinical applications. Acta Radiol 1996;37(1):3–13.

15. Kramer SC, Gorich J, Aschoff AF, et al. Diagnostic value of spiral-CT angiography in com- parison with digital subtraction angiography before and after peripheral vascular intervention.

Angiology 1998;49(8):599–606.

16. Rieker O, Duber C. Prospective comparison of CT angiography of the legs with intraarterial

digital subtraction angiography. AJR 1996;166:269–276.