PERIPHERAL ARTERIAL DISEASE (PAD)
OF THE LOWER EXTREMITIES IN DIABETES MELLITUS
EPIDEMIOLOGY AND NATURAL HISTORY
RISK FACTORS AND CLINICAL EVALUATION
INVESTIGATION OF PAD AB INDEX, DUPLEX SCAN, ANGIOGRAM
ENDOVASCULAR SURGERY IN PAD
CRITICAL LIMB ISCHEMIA
MINIMAL VASCULAR EVALUATION AND REFERRAL
PAD is one of the commonest manifestations of Diabetes Mellitus. It is one of the
many “end organ” failures caused by Diabetes Mellitus and along with neuropathy
and infection of the foot it is a leading cause of morbidity and economic loss,
probably more than coronary artery disease and cerebro-vascular disease combined!!
Though the clinical diagnosis of PAD can be achieved with ease and certainty in
most of the patients, unfortunately it is still 'missed' in many patients and places,
causing undue delay in diagnosis and therapy, leading to severe morbidity,
economic loss and frequently results in mortality. It is a sombre truth that 50% of all
extremity amputations occur in diabetic patients.
Epidemiology & Natural History:
1. Prevalence of asymptomatic PAD is difficult to determine and reported with wide
variation of 0.9 to 22%!! But in persons with diabetes it is 2 to 3 times more
2. About 3 to 6 % of the general population suffers from arterial claudication, mostly in
men. Prevalence in persons with diabetes is 4 to 5 times higher than this and is nearly
equal in both the sexes.
3. Critical Limb Ischemia (CLI) denotes advanced PVD with imminent limb loss (non-
healing ulcer, gangrene or rest pain). About 500 per million of the population develop
CLI per year, but diabetes doubles this risk!
4. Diabetic PAD is a more aggressive disease and occurs in younger patients. Rapid
progression of 'early' critical limb ischemia to gangrene occurs in 40% of the diabetic
as opposed to 9% in persons without diabetes.
5. Sudden progression from intermittent claudication to limb threatening ischemia
occurs in 35% of persons with diabetes (19% in persons without diabetes) with 21%
risk of major amputation (3 % in persons without diabetes).
6. Since vascular disease is a “systemic disease”, about half of the patients have
coronary artery / cerebrovascular disease. About a third of the patients with coronary
artery disease have PAD.
7. Several consensus statements within last couple years have designated PAD as a risk
factor, higher indicator than coronary or cerebrovascular disease for systemic
atherosclerosis. The recent TASC II (Trans Atlantic Inter-Society Consensus)
statements recommends that any patient with ankle brachial index (ABI) less than
0.90 should be considered at risk for systemic atherosclerosis and ABI might be the
easiest screening procedure to identify these patients at risk and submit them to the
best medical therapy.
Risk Factors for PAD:
Apart from Diabetes, several other risk factors could have additive effect on PAD &
progression. Smoking is an independent risk factor, which increases the odds of
developing PAD by at least 3 times, and has significant additive effect in diabetes.
Hyperlipidemia and inflammatory arteriopathies can coexist with diabetes.
Hypercoagulable states (congenital or acquired), neglected trauma can cause or
worsen the PAD. Hypertension is an important co-morbidity that can aggravate
About 90% of PAD can be diagnosed with good history and physical examination.
Claudication is the earliest and commonest symptom of PAD. Pain or cramps
typically appears in a muscle group, mostly in the calf muscles, sometimes in the
thigh or hip in aortoiliac occlusion, after walking certain distance. A short rest
relieves this and the patient can again walk the same distance i.e, the symptoms are
reproducible. It needs to be differentiated from neurogenic claudication, which can
occur with first few steps and takes a long time to recover; and the venous
claudication, which causes 'bursting' pain mostly towards the end of the day.
Since therapy for PAD (surgical or endovascular) is dictated by symptoms, it is
important to determine if claudication is 'disabling' for that person or not. It is
considered disabling if it interferes with his / her lifestyle. For, a 200-metre
claudication is not at all disabling for a 70 year old person with sedentary lifestyle,
but would be severely disabling for a young postman or policeman. It should be
emphasised that claudication is not an automatic indication for intervention of any
form, since critical limb ischemia and limb loss occur in only 5 and 1% respectively.
“Rest Pain” occurs as PAD further progresses. It typically occurs in the forefoot and
toes, especially at night and relieved by hanging the foot down or walking a short
distance. This requires intervention most of the time, as it is disabling and likely to
progress to the next stage of tissue loss (ulceration & gangrene). An ulcer in the foot
which does not show evidence of healing over 2 to 3 weeks, with good therapy, is
considered a 'non-healing' ulcer. Of note is the fact that 85% of persons with diabetes
have nonhealing ulcers prior to a major amputation. A gangrene of a part of a foot or
toe shows inadequate perfusion, of even resting tissue and would lead to limb loss,
more so with heel ulcer, as the pad of fat over calcaneous is vulnerable to ischemia.
Clinical examination in chronic arterial occlusive disease would reveal loss of hair
over toes, brittle nails, thin shiny skin, cooler skin temperature, discoloration
progressing to gangrene. Dependent rubor erythematous hue that appears on
hanging the foot down is a sign of advanced PAD, but difficult to make out in our
patients. A diligent palpation of the pulses will reveal absent or diminished pulsation
of posterior tibial &/or dorsalis pedis artery. The popliteal and femoral pulses, as are
the pulses in the abdomen, upper extremities, neck should be examined and
auscultated for a bruit. Though subjective, pulses should be graded in a standard
0 -- Absent, 1 -- Feeble, 2 -- Normal, 3 -- Prominent, 4 -- Aneurismal.
Routine laboratory investigations should include complete blood count, platelet
count, fasting blood glucose or HbA1c, S. creatinine, lipid profile and ECG.
Additional testing, dictated by patient's symptoms and findings, include further
cardiac workup, hypercoagulability screen, screening for other vascular diseases like
carotid stenosis, aneurismal disease and these should not be done routinely in all the
Ankle Brachial Index (ABI):
This simple and extremely useful measurement can be performed with a handheld
Doppler with appropriate blood pressure cuffs for arm and thighs. ABI is the ratio
between ankle and brachial pressure and is around 1. The ratio of over 0.9 is
considered normal. A claudicator has a ratio of usually over 0.7 and those with
critical limb ischemia less than 0.5 and this is a good predictor of deterioration of
PAD, with 2 ½ times increased chance of amputation. Some diabetics have non -
compressible arteries because of calcification and ABI can be falsely higher than 1.0.
A toe cuff would be useful in these patients and the toe pressure is about 10 mm of
Hg, less than the ankle pressure. An ankle pressure of 70 mm of Hg indicates a very
low risk of amputation. (Fig 39)
This combines B Mode ultrasound with colour Doppler imaging and is an extremely
useful noninvasive diagnostic tool for initial imaging and in fact in many diabetic
patients who cannot undergo angiography therapy can be based on duplex scan
findings. Most, if not all, patients with PAD should undergo this test as an initial
diagnostic test. Apart from direct imaging, duplex scan also records flow velocities
and graphic waveforms can also be recorded.
This remains the “Gold Standard” for imaging in PAD. But, it should not be used as
a screening test and should be used only in those patients in whom intervention is
contemplated, which again is dictated by symptoms and findings of other modalities
of testing. Digital subtraction angiogram has virtually replaced “standard”
angiogram, since imaging of the leg and foot arteries is much superior with usage of
lesser amount of dye. The procedure is well tolerated, with complication rate of less
than 2%, but caution should be exercised in patients with compromised renal
function and / or in the diabetic patient who is poorly hydrated, since dye induced
nephropathy can add significantly to morbidity of these patients. A good lower limb
angiogram should provide imaging of arteries from abdominal aorta to plantar arch.
Other imaging modalities like MR angiogram and CT angiogram are excellent
modalities for vascular imaging and with advancing technology, some of these may
replace the angiogram in future. CT angiogram does require a large amount of dye
and hence cannot be used in patients with renal failure. MRA is safe in patients with
CRF and might replace conventional angiogram in future.
Carbon dioxide angiogram: CO2 is a radio-opaque gas, which can be used for
imaging the arterial system. Large volumes can be injected into the arterial system
without any adverse effects and is completely excreted during the first pass through
the lungs. It is not nephrotoxic and hence can be used in patients with compromised
renal function. But the opacification is not as good as iodinated contrast agents and
the gas “breaks up” as it passes down the arterial tree. Hence it is an acceptable
contrast agent for imaging the infra renal aorta, iliac and femoral arteries. The
“medical grade CO2” used for laparoscopic insufflations is used and care should be
taken to avoid mixing of air, as this would lead to serious effects of air embolism.
Distribution of PAD in persons with diabetes is different from nondiabetic
atherosclerosis. They are more prone to have infra-inguinal and infra-popliteal
disease than aorto-iliac occlusive disease. It is important to note that the
microangiopathy does not adversely affect the outcome of vascular reconstruction in
Therapy for Intermittent Claudication:
Therapy involves a four-pronged approach as recommended by National Cholesterol
Education Program (NCEP-Panel III)
1. Life style modification.
2. Risk factor reduction.
3. Supervised exercise program and medical therapy.
4. Revascularization in severe cases.
Life style and risk factor modification involves cessation of smoking and tobacco use
with counseling and assistance as needed. Good glycemic control, control of
hypertension, treatment of dyslipidemias. Supervised exercise program and
structured training on a treadmill have been shown to be superior to just counseling
about exercise program.
Pharmacotherapy involves use of circulation enhancing drugs and at present
cilastazole (to be used with caution in patients with LVF) and L-Carnitine are the
drugs available for treatment of claudication. Pentoxyfilline has not proven to be
better than placebo for the treatment of claudication. Anti-platelet agents Aspirin and
clopidogrel should be used in all patients with PAD. As the prices come down
clopidogrel could be preferred as it has less GI side effects Though they do not have
direct effect on PAD or its symptoms, they are documented to reduce cardiovascular
morbidity and mortality in these patients. Use of statins has been shown to be
beneficial even in normolipemic patients.
Control of risk factors and lifestyle modifications are an important and integral part
of the treatment of PAD. Cessation of smoking, control of hyperlipidemia and
control diabetes with good glycemic control should be achieved. But, unfortunately,
glycemic control does not necessarily mean arrest of progression of PAD.
Since neuroischaemic ulcers in the foot are more common than PAD alone, a multi
disciplinary approach to Foot problems cannot be stressed enough. Simple
preventive measures will reduce the amputation rate in diabetics by about 50%.
Pharmacotherapy in PAD has limited role to play. Pentoxyfilline, a haemorrheologic
agent, was thought to have a role in claudicators, but studies have shown it not
better than placebo. Cilastazole does improve claudication distance in significant
number of patients and should be used as initial therapy in claudicators. None of
these drugs (eg. I.V. pentoxyfilline) are of any use in critical or acute limb ischemia.
Vasodilators are mentioned here, only to be condemned, as they have no role to play,
except in certain select circumstances. Antiplatelet drugs are used in arterial
thromboembolism, but should be used in all PAD patients lifelong to decrease the
cardiac and cerebrovascular mortality and morbidity. Anticoagulation has limited
role to play and prostanoids are used in non reconstructible critical limb ischemia.
Surgical Therapy remains the mainstay to achieve revascularisation of PAD of lower
limbs, especially in diabetics. Most of these patients have long segment;
infrapopliteal occlusions and majority are amenable to vascular bypass procedures.
The selection of patients shall be stringent and non disabling claudicator should not
be subjected to these procedures. Surgical and interventional procedures
(angioplasty, stenting) should be offered to those who fail to improve on good
medical therapy, but should be considered in all patients with rest pain and tissue
The “bypass” procedures can be performed to any level in the lower extremities
from aorto iliac reconstruction to bypass to foot arteries. Most of the “bypass”
procedures done in diabetic PAD is to the paramalleolar arteries posterior tibial,
anterior tibial or peroneal artery near the ankle. The selective beta blockers like
metoprolol or bisoprolol are not detrimental to PAD but are definitely
cardioprotective as well as beneficial in preventing cerebrovascular events in the
perioperative period. They could be continued for about three months in the post
operative periods for these benefits. ARBs and ACEI are also protective in this
The goal of therapy is functional limb salvage, not necessarily long term graft
patency. Proximal reconstructive procedures (aorto iliac femoral bypass
procedures) have a 5 and 10 year patency rate up to 80%. Infrainguinal /
infrapopliteal bypass procedures have much lower patency rates (about 50-60% at 3
years) but the limb salvage remains high, about 80-90%. Once the initial wound heals
with risk factor control, appropriate lifestyle medication and foot care, further
ischemic limb loss can be prevented.
Artificial grafts (Dacron, PTFE) are ideally suited for aorto iliac femoral
reconstruction. Femoral popliteal bypasses with artificial graft do nearly as well as
saphenous vein. Infra- popliteal bypass should be performed with vein graft
wherever possible, since artificial grafts do poorly in these locations.
Endovascular Surgery / Intervention:
These are minimally invasive procedures ideally suited for certain lesions. These
catheter based techniques are gradually replacing some surgical procedures and
many more will be added to this list in future. Balloon angioplasty with or without
stenting is ideally suited for short segments, stenotic lesions of iliac artery and
selected lesions in femoral and distal vessels. A variety of lesions are now being
treated with these methods, but these are expensive procedures and their usage is
limited because of it. The advantages are short hospitalization and rapid return to
The lesions are divided into four categories Grades A and B are usually short
segment stenosis and occlusions and these can be treated with endovascular
interventions. Grade C and D lesions usually require surgical intervention. Primary
stenting is indicated in iliac lesions, but has not changed the outcome in femoral and
distal vessels and their outcome is no better than balloon angioplasty alone. With
inexorable progress of technology, more such procedures will be performed at a
lower cost in future.
Amputation is the “finale” of either failure to treat or failed treatment of severe limb
ischemia. Every attempt should be made to obtain functional limb salvage, especially
in persons with diabetes, since many have multi-system involvement and loss of a
limb adds markedly to their disability. It is felt by some in India that amputation is
better than vascular reconstruction as it is a 'quicker and cheaper' option. This is far
from the truth and the following facts should be borne in mind.
Facts about amputation for Critical Limb Ischemia:
1. In the US, about 150,000 per year require amputation for the legs. In India, this figure
is likely to be much higher.
2. Perioperative mortality for below knee amputation is about 8 to 10% and that of
above knee amputation is 15 to 20%. The mortality for vascular reconstruction
remains lower at 2 to 5 % as is the morbidity.
3. 40% die within 2 years of their first major amputation.
4. A second amputation is required in 30% of the patients.
5. Only 50% of the patients with below knee amputation and 25% of those with above
knee amputation will ever achieve full mobility. The figures are probably worse in
India since “modern” prosthesis may not be available or affordable to all.
6. The mid and long term cost of amputation is higher than vascular reconstruction.
7. There is no effective drug therapy in critical limb ischemia and usage of vasodilators
and others only delay proper therapy and entail unnecessary cost.
8. The quality of life of amputees is poor and several psychological testings have shown
this to be similar to patients with cancer in critical and even terminal phases.
9. Even the elderly and those with multiple medical problems tolerate vascular bypass as
well, if not better, than amputation. Our experience at Jain Institute of Vascular
Sciences, Bangalore has shown that limb salvage in these diabetic patients is about
90%, though our mortality and morbidity is higher than quoted in literature. It is
because of late presentation and referral to us and most of the patients have
10. About 70% of over 600 lower limb vascular “bypass” procedures performed by us in
last five years are on persons with diabetes and over half of these were to infra
popliteal arteries. Nearly all the diabetic patients had at least one other comorbidity.
The out comes were: Graft failure 7%, Post bypass amputation 6%, Mortality 7%.
There is however a significant overlap in these figures (eg. Patient who had failed
bypass and also underwent amputation, has also a high chance of mortality) and
hence the over all mortality and morbidity is about 9%, which means over 90% 0f
these patients leave the hospital with intact functional limbs.
There is a high prevalence of PAD in persons with diabetes, resulting in limb loss,
which can have devastating effects on these patients. With appropriate therapy,
functional limb salvage can be obtained in a majority of the patients and this can be
sustained by risk factor modification and foot care. Even high-risk patients do well
with vascular reconstructive procedures rather than amputation and hence every
attempt should be made to avoid major amputation in these patients.
Minimum Vascular Evaluation and Care For Patients with Diabetic Foot Problem
Since all persons with diabetes, irrespective of gender, are at a high risk of Peripheral
Arterial Disease, clinical examination of the Vascular System, especially of the lower
limbs should be carried out every 3 months, in asymptomatic patient. This should
include notation of any ischemic changes in the feet and palpation of femoral,
popliteal, Dorsalis pedis and posterior tibial pulses. Appropriate record should be
maintained of the clinical findings.
When a patient develops claudication, non- healing ulcer or other form of tissue loss,
rest pain, he / she should be referred to the vascular surgeon or to a surgeon with
special interest in vascular diseases, as soon as possible.
If vascular occlusion is suspected on clinical exam, it is recommended that non
invasive testing (duplex scan) be performed and any further testing especially
invasive testing like arteriogram be performed only after evaluation by a vascular
When a diabetic patient with symptoms suggesting acute limb ischemia presents
himself, urgent referral to a vascular surgeon is needed to prevent amputation.
Administration of analgesics and heparin before referral is acceptable, but no other
medication is of any proven value in this situation.
Haemorrheologic agents like pentoxyfilline can be used only in claudicators, but the
drug of choice at present is cilastazole. These two have no documented value in
diabetic foot ulcers and acute ischemia. Use of other drugs like vasodilators is not
recommended as they have no proven value. Antiplatelet agents have definitive role
to play in arterial diseases but have no effect in diabetic foot or acute ischemia.
Even minor surgical procedures in diabetic foot should be preceded by adequate
In any diabetic foot, which has vascular insufficiency, arterial reconstruction should
be attempted, if functional limb salvage can be obtained.