CLINICAL MEDICINE | CASE REPORT

A PATIENT WITH DIABETES MELLITUS TYPE 2 WITH

ACUTE LIMB ISCHEMIA
I Nyoman Agus Subagiartha∗ , Ida Bagus Aditya Nugraha∗∗,1 and Wira Gotera∗∗
∗ Internal Medicine Residency Program, Medical Faculty of Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia, ∗∗ Endocrinology and
Metabolic Division, Department of Internal Medicine, Medical Faculty of Udayana University/Sanglah General Hospital, Denpasar, Bali Indonesia

ABSTRACT Acute Limb Ischemia (ALI) is one of the complications from diabetes mellitus (DM) that presents as sudden
lower limb ischemia that can result in amputation. The aetiology is broadly divided into embolism and thrombosis with
various comorbidities. ALI symptoms are abrupt with pain, numbness, and coldness of the lower limb, and paresthesia,
contracture, and irreversible purpura will appear with the exacerbation of ischemia. Severity and treatment strategy
should be determined based on physical and image findings. ALI is a serious disease requiring urgent treatment, and it
is essential to promptly perform the best initial treatment that can be performed at each facility. The different therapeutic
techniques are presented, ranging from pharmacological (thrombolysis), interventional techniques (thromboaspiration,
mechanical thrombectomy), established surgical revascularization, and minor or major amputation of necessity. We
reported a male, 57 years old, with type 2 diabetes mellitus and acute limb ischemic in pedis dextra. This patient
undergoes the amputation above the knee in pedis dextra to treat acute limb ischemic and get a good prognosis.

KEYWORDS Diabetes mellitus, Acute limb ischemia, Amputation, Good prognosis

Introduction
Diabetes mellitus type 2 (DMT2) is known to cause various
microvascular and macrovascular complications.[1,2] One of the
complications of DMT2 is Acute Limb Ischemia (ALI) which can
be defined as a condition in which there is a sudden decrease in
leg perfusion usually caused by thrombus and embolism and
occurs within 14 days of the onset of the complaint.[3]
The incidence of acute limb ischemia is about 1.5 cases per
10,000 people per year, with a mortality rate of 15-20% within 30
days and the incidence of amputation reaching 10-15%. Symp-
toms develop over hours to days and vary from intermittent
episodes of claudication to pain in the soles of the feet or legs
when the patient is resting, paresthesias, muscle weakness, and
paralysis of the affected extremity.[4] Physical findings could be
found, such as pulselessness in the distal part of the occlusion,
Copyright © 2022 by the Bulgarian Association of Young Surgeons
DOI: 10.5455/IJMRCR.172-1627886961
First Received: August 2, 2021
Accepted: January 25, 2022
Associate Editor: Ivan Inkov (BG);
1
Corresponding author: Ida Bagus Aditya Nugraha; E-mail:
ibadityanugraha@gmail.com
the skin feeling cold and pale or mottled, decreased nerve sensa-
tion, and decreased muscle strength. These signs are commonly
abbreviated as the 6 Ps: Paresthesia, Pain, Pallor, Pulselessness,
Poikilothermia (impaired body temperature regulation), and
Paralysis.[5] Delay in treating ALI patients will increase the risk
of amputation.[6]
Acute Limb Ischemic (ALI) is an emergency in which "Time is
limb", and specific treatment must be started immediately. The
golden period is six hours before irreversible muscle damage
occurs. As more society acknowledges the signs and symptoms
of ALI, fewer people will lose limbs due to amputation, which
is the final management of the worst category of this arterial
disorder. If a person is suspected of having ALI in his limbs,
multidisciplinary action must be taken immediately.
Case report
A 57-year-old man from Palembang, an Indonesian citizen, came
with a complaint that his right foot was said to be rotting and
spreading from the tip of the right toe to the shinbone of the
right foot. At first 10 days before admission to the hospital, the
patient’s right foot was pierced by a nail at home without the
patient realizing it but there were no complaints such as bleeding
or pain. However, after 3 days of being pierced by the nail, the

I Nyoman Agus Subagiartha et al./ International Journal of Medical Reviews and Case Reports (2022) 6(8):19-23
nail wound became wider and blackened from the sole to the
shin of the patient’s right leg. The patient also complained of
fever throughout the body and pain in the sole to the right leg’s
shin since 3 days after being pierced by a nail. The patient has a
history of Diabetes mellitus (DM) since 16 years ago. The patient
was taking metformin 500 mg every 12 hours but not regularly.
Initially, the patient had a smoking habit but had stopped 5
years ago when the patient developed DM. On physical exami-
nation, the patient’s general condition was good; consciousness
was alert. Blood pressure 120/70 mmHg, pulse 80x/minute,
respiratory rate 22x/minute, and axillary temperature 36.40C.
There were no anemic conjunctiva and icterus sclera on eye ex-
amination in both eyes. Thoracic examination revealed a single,
regular S1S2 heart sound, no murmur. Breath sounds were vesic-
ular, no rhonchi or wheezing were heard. The lower extremities
were warm. Enlargement of regional cervical, axillary, and in-
guinal lymph nodes were not found. The patient’s body mass
index (BMI) was 22.2 kg/m². On examination of the patient’s
local status on the crural dextra to the right pedis, there were
blisters on the dorsum, and plantar pedis appeared, swelling
(+), redness (+), necrotic (+). The posterior tibial, dorsalis pedis
and popliteal arteries were not palpable, tenderness in the cruris
area above the wound, limited ROM because of pain. The pa-
tient underwent a complete blood count with the results: leuko-
cytes 18.2 x 10³/µL; neutrophils 16.5 x 10³/µL; lymphocytes 0.47
x 10³/µL; monocytes 1.54 x 10³/µL; eosinophil 0.01 x 10³/µL;
basophil 015 x 10³/µL; the patient’s hemoglobin was within
normal limits of 11.0 g/dL; hematocrit 30.8%; platelets 211 x
10³/µL. The patient was also tested for blood chemistry which
found BUN 44.1 mg/dL; Creatinine 2.10 mg/dL; SGOT 35.1
U/L; SGPT 54.1 U/L; BSA 569 mg/dL; Albumin 2.80 g/dL; Na
121 mmol/L; K 3.75 mmol/L, HBA1C 12.2%. On examination
of hemostasis, PPT 12.4; APTT 30.8; INR 1.10. Complete urine
examination revealed cloudy urine, +3 proteinuria, leukocytes
sediment 1.3/lpb, erythrocyte sediment 3.7/lpb. Blood pH was
normal on examination of blood gas analysis, but there was an
increase in pCO2 42 mmHg, pO2 74 mmHg, Beecf 2.0, HCO3
– 26.6 mmol/L. The patient underwent a pedis/oblique X-Ray
showing neurarthropathies with surrounding gas gangrene. On
X-Ray, the ap/lat cruris showed gas gangrene as high as the
distal femur to the right ankle. The patient was diagnosed with
Susp Acute Limb Ischemia (ALI) dextra; Type II Diabetes melli-
tus (DM), Diabetic foot dextra Wagner V, Sepsis; ACKD e.c susp
prerenal on CKD e.c susp DKD; Hypoalbuminemia e.c. chronic
inflammation; asymptomatic chronic hyponatremia euvolemic
hypoosmolar e.c susp loss; Paroxysmal AF. The patient was
treated with IVFD NS 20 dpm, DM Diet 1900 kcal/day, injection
of metronidazole 500 mg every 8 hours, injection of levofloxacin
500 mg every 24 hours, injection of ceftriaxone 2 g every 12
hours, drip insulin 2 units/hour. The patient was consulted to
the vascular surgery department and planned for immediate
thrombectomy and administration of heparin 5000 units every
24 hours. The patient was also consulted by a cardiologist and
diagnosed with atrial fibrillation (AF). After undergoing treat-
ment for 3 days, the patient underwent an amputation above
the knee dextra by a vascular surgeon.
Discussion
Acute Limb Ischemia (ALI) is a condition in which there is a sud-
den decrease in blood flow to the extremities, which causes dis-
turbances in the ability to move, pain or signs of severe ischemia
within two weeks and generally acute limb ischemia is caused
I Nyoman Agus Subagiartha et al./ International Journal of Medical Reviews and Case Reports (2022) 6(8):19-23
Figure 1: Patient’s Right Leg.
by an acute occlusion process or the presence of atherosclero-
sis.[6] As a result of acute ischemia, tissue hypoxia that causes
irreversible changes in skeletal muscle and peripheral nerves.
The incidence of acute limb ischemia is 1 per 10,000 cases per
year, with an average age of 60 to 70 years and 52.7% in males.
In this case, we found a 57-year-old male patient who came with
complaints of a sudden blackening and rotting of his right leg 1
week before his admission to the hospital.
Risk factors for ALI include coronary artery disease (29%),
heart failure (19.4%), stroke (26.9%), peripheral arterial dis-
ease (41.9%). Peripheral artery disease is often associated
with various risk factors, including smoking (68.8%), hyper-
tension (69.2%), diabetes mellitus (12.9%), and hyperlipidemia
(35.5%).[3] The causes of ALI can be broadly divided into throm-
bus, embolism and trauma. An embolus often occlude the aor-
toiliac bifurcation, femoral bifurcation, or popliteal trifurcation.
Over the last few decades, the aetiology of cardioembolic events
has evolved. Embolism caused by rheumatic mitral stenosis with
atrial enlargement is rare because the prevalence of rheumatic
valvular heart disease has now decreased substantially.[7] Age-
related atrial fibrillation and left ventricular dysfunction with
thrombus formation at the apex are the most common causes
of cardioembolic events. Less common causes include endo-
carditis, intracardiac myxoma, or paradoxical embolism caused
by a patent foramen ovale that allows the transit of a throm-
bus in the vein into the arterial circulation. Thrombotic limb
ischemic is based on a peripheral arterial disease and causes
ischemia as a result of a chronic and static obstruction in the
crushed blood vessels and obstructs the blood vessels in the
limbs. Trauma can cause ALI in a non-iatrogenic manner, in-
cluding fractures and dislocations of the limbs, blunt force in-
juries, or stab wounds.[7,8] The sudden cessation of arterial flow
to the extremities triggers a complex pathophysiological pro-
cess. Malperfused tissue will undergo metabolic changes, from
aerobic metabolism to anaerobic metabolism. Changes in the
lactate-pyruvate ratio will increase lactate production, increase
hydrogen ion concentrations, and eventually cause acidosis. Pro-
gressive ischemia leads to cell dysfunction and death. Mus-
cle hypoxia reduces intracellular adenosine triphosphate (ATP)
stores and causes dysfunction of sodium/potassium-ATPase
and calcium/sodium channels, leading to leakage of intracellu-
lar calcium into myocytes. Intracellular free calcium levels will
increase and interact with actin, myosin, and proteases, causing
necrosis of muscle fibres. Along with damage to microvascular
integrity and cell membranes, potassium, phosphate, creatinine
kinase and intracellular myoglobin are released into the systemic
circulation. Furthermore, reperfusion increases the changes that
occur in these cells. Muscle and nerve tissue are quite susceptible
to ischemic injury, so the presence or absence of a neuromotor
deficit is a very important point to assess the severity of acute
limb ischemia. The irreversible muscle damage will begin as
early as 3 hours after ischemia occurs, and this damage will
be complete after reaching 6 hours.[9] In addition to myocyte
injury, skeletal muscle injury will be followed by progressive
microvascular damage. The more severe the cellular damage,
the greater the microvascular changes. In conditions of muscle
necrosis, the microvascular flow stops within a few hours. In
theory, it takes about 6 hours to cause irreversible functional
injury. This time span may be longer in conditions of the ex-
tremity with contralateral blood flow. Skeletal muscle ischemia
and reperfusion stimulate some additional inflammatory cas-
cades involving complement activation, increased expression
of adhesion molecules, cytokine release, eicosanoids synthesis,
free radical formation, cytoskeletal changes, adenine nucleotide
depletion, alterations in calcium and phospholipid metabolism,
leukocyte activation, and endothelial dysfunction. Interleukin
(IL)-1β and tumour necrosis factor (TNF)- can be detected im-
mediately after reperfusion and trigger adhesion molecules on
the endothelial cell surface, increase capillary leakage, and stim-
ulate the production of IL-6 and IL-8, which further increases
endothelium permeability, destroys endothelial integrity, and
activates leukocytes. The reperfusion syndrome has two compo-
nents. The local response to reperfusion leads to tissue swelling,
whereas the systemic response can lead to multiorgan failure
and death. This systemic response causes intervention failure in
advanced and irreversible limb ischemia. Thus, reperfusion of
large muscle groups that occurs with advanced ischemic injury
and tissue necrosis will result in large amounts of toxic inflam-
matory mediators released into the systemic circulation. The
deleterious effect of the reperfusion process can cause patients
with irreversible ischemic injury to be amputated.[7,9] In this
case, the patient came with a complaint of a blackened right leg
and a sudden widening wound. The patient has a history of
the previous disease, type 2 diabetes mellitus, which has been
suffering since 16 years ago. Diabetes mellitus is one of the risk
factors in this patient accompanied by patients who initially also
had a smoking habit, currently with the highest blood sugar
level of 569 mg/dL and accompanied by heart problems in the
form of atrial fibrillation from the ECG picture at the time of
initial examination at medical triage.
In the history, complaints occur in <50% of patients, namely
intermittent claudication (pain, cramps, numbness, or muscle
fatigue during activity and disappears with rest), which is felt
distal to the site of occlusion, for example, in the buttocks, hips,
and thigh muscles if the occlusion is in the aortoiliac. Mean-
while, pain in the calf is felt if the occlusion is in the popliteal,
femoral artery. Another complaint is that the patient feels cold
or numbness in the feet and toes, often felt at night when the
legs are horizontal and increases when the legs are in a hanging
position.[9] At first, the feet only blackened on the soles of the
feet and then suddenly spread to the right calf.
Classic symptoms and findings often obtained in patients
I Nyoman Agus Subagiartha et al./ International Journal of Medical Reviews and Case Reports (2022) 6(8):19-23
with acute limb ischemia are often known as the 6 Ps: Pulse-
lessness, pallor, pain, poikilothermia, paralysis, and paresthesia.
Pain is the most common symptom and increases with the sever-
ity of ischemia. Pallor (pallor) is an early finding in an ischemic
extremity caused by complete emptying and vasospasm of the
arteries. The subsequent stagnation of the microvascular circu-
lation will cause skin breakdown, in which the skin will turn
pale when pressed. As the ischemic condition persists, there
will be paresthesia, and then numbness or numbness replaces
the pain, which causes the patient and the doctor to miss the
patient’s diagnosis. In the final stage, there will be paralysis,
peeling of the skin, the skin looks pale, the skin is stiff and shiny
like marble, which strengthens the suspicion that irreversible
ischemic injury has occurred.[9] In this case, the right crural to
the right pedis of the patient, showed there were blisters on the
dorsum and plantar pedis, swelling (+), redness (+), necrotic (+).
The posterior tibial and dorsalis pedis arteries were not palpable,
tenderness in the cruris area above the wound, limited ROM
because of pain.
Physical examination may reveal decreased or absent pulses
distal to the occlusion, audible bruits, and atrophic muscles.
There is a thickening of the nails in severe cases; the skin looks
smooth and shiny, decreased skin temperature, hair loss, pale or
cyanosis. Ulcers or gangrene may also be found. Examination
of leg reflexes can also be decreased due to ischemic neuropa-
thy.[10] There are clinical criteria that can be used to determine
the severity and appropriate intervention strategies in dealing
with cases of ALI, known as the Rutherford Classification.
Supportive examination modalities that can be carried out
include screening risk factors and comorbid diseases. To estab-
lish the diagnosis as a standard is to use arteriography. In the
patient, we encountered complaints of blackening of the right
foot, which had been experienced since 10 days before admis-
sion to the hospital and had worsened in the last 4 days starting
with numbness and coldness in the toes, which had been experi-
enced 2 weeks ago, blackening from the tips of the big toes and
over time it extended to the knee and was accompanied by pain
that lasts continuously even at rest so that the patient could no
longer walk. On physical examination, there was necrosis in the
pedis and cruris region with weakened dorsal popliteal artery
pulsation. Based on Rutherford’s classification, the patient’s
case can be classified into stage III. The patient had not been
subjected to a supporting examination because of consideration
of the clinical condition of the patient’s leg, so it was decided to
perform amputation surgery immediately.
ALI requires immediate treatment. There are three modalities
of treatment options in patients with ALI, namely medical ther-
apy, endovascular intervention, and surgery. Management of
patients with acute limb ischemia aims to reduce cardiovascular
risk, improve limb function, prevent progression to ischemia and
maintain limb viability. Medical therapy consists of anticoagu-
lant therapy with warfarin. The duration of treatment depends
on the aetiology of ALI. In patients of unknown thrombus ori-
gin, then anticoagulation is given for one year. Thrombophilic
patients with ALI require long-term anticoagulation, sometimes
for lifetime treatment.[11,12] If there are no contraindications
(such as acute aortic dissection with multiple head trauma), hep-
arin is given to stop the spread of the thrombus. Amputation in
patients is based on:
1. The patient belongs to Rutherford category III.
2. Failure of endovascular thrombolytic agent therapy.
Table 1 Rutherford Classification for ALI [5]
Sensory Muscle Arterial
Category Description Vein Doppler
Loss Weakness Doppler
No immediate
I: Viable None None Audible Audible
limb threatened
IIA: Salvagable if Usually Often
Marginally promptly treated Minimal Audible
none inaudible
threatened
More than
IIB: Salvagable with the toes, Mild -
Immediate immediate pain when Inaudible Audible
moderate
threatened revascularisation resting
III: Major tissue loss
or permanent Profound Paralysis
Irreversibly Inaudible Inaudible
nerve damage anesthetic (rigor)
damaged
inevitable

3. Necrosis of the right leg that cannot be saved. defined as a condition in which a sudden decrease in leg perfu-
sion usually caused by thrombus and embolism occurs within
14 days of the onset of the complaint. Delays in the management
of ALI patients will increase the risk of amputation.

Funding
This work did not receive any grant from funding agencies in
the public, commercial, or not-for-profit sectors.

Figure 2: Therapy algorithm in patients with acute limb is-
chemia.[4,5]
Speed is the main management principle in patients with
acute limb ischemia. Within 6 hours, this condition will lead
to permanent tissue damage unless immediately revascular-
ized. Revascularization can be performed by endovascular or
endovascular revascularization surgery. The basic principle be-
hind endovascular therapy is to restore arterial flow, either by
lysing the thrombus or by finding and removing the underly-
ing lesion, thereby eliminating the need for surgery or reducing
the length of surgery. While amputation is the last option if
revascularization fails.[8,10] The patient received therapy with
20 dpm NS IVFD, DM Diet 1900 kcal/day, Metronidazole in-
jection 500 mg every 8 hours, Levofloxacin injection 500 mg
every 24 hours, Ceftriaxone injection 2 g every 12 hours, Novo-
rapid injection 3 units per main SC meal, Lantus injection 8 units
every 24 hours SC. The patient was consulted to the vascular
surgery department and planned for immediate thrombectomy
and administration of heparin 5000 units every 24 hours. Af-
ter undergoing treatment for 3 days, the patient underwent an
amputation above the knee dextra by a vascular surgeon. The
patient is currently in the process of postoperative recovery. The
patient was discharged after undergoing treatment for 10 days
postoperatively.
Conclusion
Conflict of interest
There are no conflicts of interest to declare by any of the authors
of this study.
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