Diabetic foot

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2] Vishnu Vardhan Serla M.B.B.S. [3] Usama Talib, BSc, MD [4]

Diabetic foot ulceration is one of the well known complications of diabetes and it is associated with high rate of hospitalization based on numerous studies. The discovery of the association between diabetes, foot ulceration, and subsequent infection dates back to the 1850s. Diabetic foot is classified based on the ulcer‘s features in order to assist with clinical decision-making regarding the need for oral or parenteral antibiotics, outpatient management, hospitalization, and surgical intervention. There are multiple methods of classification for diabetic foot. Neuropathy, ischemia, and trauma are three main pathogenesis of diabetic foot. Neuropathy is the most common and is responsible for more than 60% of diabetic foot cases. Motor nerve involvement can lead to some mechanical changes in the foot of a diabetic patient, which causes more plantar pressure and higher risk of callus formation. Each and every factor leads to a higher rate of skin breakdown and ulceration. Some genetic associations (such as the MAPK14 gene located on chromosome 6, decreased expression of certain cytokines and growth factors, and the HSPA1B genotype) have been explained in diabetic foot development. Charcot arthropathy, some psychosocial conditions, necrotizing fasciitis (NF), vitamin D deficiency, tinea pedis, onychomycosis, and diabetic retinopathy are associated conditions in diabetic foot. Microorganisms such as staphylococcus aureus, pseudomonas aeruginosa, proteus mirabilis, escherichia coli, and bacteroides fragilis are responsible for diabetic foot ulcer infection. Diabetic foot must be differentiated from other diseases that cause foot ulceration, erythema, swelling, and skin lesions, such as skin and soft-tissue infections, gas gangrene, cellulitis, deep venous thrombosis, and inflammatory disorders. The incidence of diabetic foot ulcer is approximately 1,500 per 100,000 diabetic individuals world wide. The 5 year risk of mortality in diabetic patients with a foot ulcer is 2.5 times higher than diabetic individuals without a foot ulcer. Based on a systematic review and metanalysis done on diabetes patients, diabetic foot was more common among older patients. White people develop diabetic peripheral neuropathy (which is a serious risk factor for diabetic foot) more frequently. Male gender is more prone to diabetic foot, compared to females. There are numerous risk factors for diabetic foot development in a diabetic patient, such as poor glycaemic control, inappropriate foot care and footwear, foot deformities, history of previous foot ulcer or amputation, high body mass index, and poor socioeconomic status. For a desired diabetic foot screening, it is critical to perform a careful foot examination at least annually in diabetic patients who are over the age of 15. Nevertheless, there are some risk stratification systems that can provide a better understanding of how often foot screening should be performed based on each patient. The healing process of diabetic foot usually takes a long time (2-5 months) with proper treatment and it can become slower in patients with elevated body mass index or osteomyelitis. Diabetic foot ulcers can cause numerous complications, such as sepsis, osteomyelitis, gangrene, lower limb amputation, and death. History of previous foot ulceration and poor glycemic control are two common positive histories in many patients suffering from diabetic foot. Neuromuscular examination of patients with diabetic foot is usually normal, except in their foot. Findings such as impaired vibration and pressure perception, position sense, and abnormal thresholds for warm thermal perception favor the diagnosis of sensory neuropathy. It is critical to check the extremities for findings such as ulcers, peeling skin, dilated or varicose veins, shiny skin with reduced hair distribution, and broken nails while examining for diabetic foot. For detection of the main responsible microorganisms, biopsy or, curettage or aspiration, of a tissue sample is recommended. It is recommended to obtain a sample from discharge of the ulcer‘s base. Although a plain X-ray is not successful in osteomyelitis diagnosis within the first weeks of involvement, it is recommended to be performed in any diabetic foot patients with a deep or enduring ulcer. Magnetic resonance imaging (MRI) is specific for osteomyelitis diagnosis. This imaging modality has a 90% sensitivity and an 85% specificity in diagnosis of diabetic foot ulcers. Appropriate wound care is essential for the management of all diabetic foot ulcers. Uninfected diabetic ulcers do not require antibiotic therapy. On the contrary, for acutely infected wounds, empiric antibiotic therapy with coverage against Gram-positive cocci should be started right after obtaining a post-debridement specimen for aerobic and anaerobic cultures. One of the centerpieces of diabetic foot treatment is debridement of necrotic and fibrotic tissues as well as calluses. Foot ulcers can be prevented by frequent physical examinations, proper glycemic control, good foot hygiene, diabetic socks and shoes, and by avoiding injury.

The discovery of the association between diabetes, foot ulceration, and subsequent infection dates back to the 1850s. Significant breakthroughs in the management of diabetic foot wounds include the introduction of surgical debridement in the early 1900s by Frederick Treves. He also introduced the critical role of footwear in diabetic foot ulcers. Furthermore, the discovery of penicillin in 1928 by Alexander Fleming, significantly reduced the mortality rate of diabetic foot patients and their related complications. Throughout the 20th century, advances in surgical limb revascularization and the advent of angioplasty drastically reduced the need for amputation. The latter method remained the mainstays of diabetic foot management in the 2004 and 2012 Infectious Disease Society of America guidelines.

Diabetic foot is classified based on ulcer‘s features in order to assist with clinical decision-making regarding the need for oral or parenteral antibiotics, outpatient management, hospitalization, and surgical intervention. There are multiple methods of classification for diabetic foot. One of them has been published by The Infectious Disease Society of America (IDSA) in their 2004 guidelines and has been mainly focused on the extent of infection and inflammation of the ulcer. In addition, another similar classification system has been released by The International Working Group on the Diabetic Foot (IWGDF) in 2012. The aforementioned systems were externally validated in a longitudinal study to assess prognostic value, which demonstrated increased risk for amputation among patients with infections classified as severe. Another widely accepted diabetic foot ulcer classification is the Wagner ulcer classification system, which uses some ulcer‘s features such as depth, in addition to presence of osteomyelitis or gangrene.

Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. Neuropathy, ischemia, and trauma are three main pathogenesis of diabetic foot. Neuropathy is the most common and is responsible in more than 60% of diabetic foot cases. Factors such as high blood glucose, reactive oxygen species, insufficient oxygenation of the nerves, and inflammation leads to neuropathy development in diabetic patients and it gets worse with alcohol use and smoking. Neuropathy can involve motor, autonomic, or sensory nerves and is able to involve both large and small fibers. Motor nerve involvement can lead to some mechanical changes in the foot of a diabetic patient, which causes more plantar pressure and a higher risk of callus formation. Each and every factor leads to a higher rate of skin breakdown and ulceration. Autonomic neuropathy leads to anhidrosis and impaired function of oil glands, subsequent skin dryness, higher chance of skin breakdown, and ulcer formation. Diabetic patients with sensory neuropathy are more prone to ulcer formation and related complications, since they don’t feel pain with ever-deepening ulcers. Ischemia is the second best known pathogenesis of diabetic foot that could occur due to a higher rate of lower limb atherosclerosis in diabetic patients, compared to the normal population. Diabetes related complications such as Micro and macrovascular complications further intensify ischemia. Ischemic changes can be discovered by an impaired ankle brachial index (ABI). Trauma to the foot usually acts as a trigger for diabetic foot. A defective hypoxic response has been explained in diabetic foot, which is related to a transcription factor named hypoxia‐inducible factor‐1 (HIF‐1). Lower levels of HIF‐1 in biopsies of diabetic foot could be related to its role in wound healing. Some genetic associations (such as MAPK14 gene located on chromosome 6, decreased expression of certain cytokines and growth factors, and the HSPA1B genotype) have been explained in diabetic foot development. Charcot arthropathy, some psychosocial conditions, necrotizing fasciitis (NF), vitamin D deficiency, tinea pedis, onychomycosis, and diabetic retinopathy are associated conditions in diabetic foot. On gross pathology, the most common site of ulceration is on the soles of the feet, under the metatarsal head with various depths and possible anatomical deformities of the foot. In microscopic evaluations of the ulcers, evidence of necrosis, hyperkeratosis, fibrosis, inflammation, cellular debris, granulation tissue, and angiogenesis have been found.

Conditions such as peripheral neuropathy and ischemia are two common causes of diabetic foot ulcer formation. Decreased sensation due to peripheral neuropathy increase the risk of trauma which is another known cause of ulcer formation. Microorganisms such as staphylococcus aureus, pseudomonas aeruginosa, proteus mirabilis, escherichia coli, and bacteroides fragilis are responsible for diabetic foot ulcer infection.

Diabetic foot must be differentiated from other diseases that cause foot ulcerations, erythema, swelling, and skin lesions, such as skin and soft-tissue infections, gas gangrene, cellulitis, deep venous thrombosis, and inflammatory disorders.

The incidence of diabetic foot ulcers is approximately 1,500 per 100,000 diabetic individuals world wide. Just among US veterans, the incidence of active diabetic foot ulcers is approximately 500 per 100,000 individuals. On the other hand, the incidence of active diabetic foot ulcers in the United Kingdom has been estimated to be 220 per 100,000 individuals. Furthermore, its prevalence has been reported as 170 per 100,000 individuals among the United Kingdom population. The 5 year risk of mortality in diabetic patients with a foot ulcer is 2.5 times higher than diabetic individuals without a foot ulcer. Based on 2 studies with different follow up durations, the mortality rate of diabetic foot has been estimated as 10% and 24% in a 16 month and a 5 year follow up, respectively. Based on a systematic review and metanalysis done on diabetes patients, diabetic foot was more common among older patients. White people develop diabetic peripheral neuropathy (which is a serious risk factor for diabetic foot) more frequently. In 1987, Borch-Johnsen et al. described a male preponderance for the development of severe microvascular complications and diabetic foot disease is not an exception to this rule. The highest prevelance of diabetic foot has been reported in North America. In contrast, Oceania has the lowest prevelance of diabetic foot.

There are numerous risk factors for diabetic foot development in a diabetic patient, such as poor glycaemic control, inappropriate foot care and footwear, foot deformities, peripheral arterial disease, peripheral neuropathy, history of previous foot ulcer or amputation, infection, high body mass index, and poor socioeconomic status. Other comorbidities such as hypertension and dyslipidemia are also responsible as risk factors for diabetic foot ulcerations.

The main focus of diabetic foot screening should be on peripheral neuropathy detection, since foot ulcer development is rare in the absence of neuropathy. In addition to examining the peripheral neuropathy, physicians should search for any evidence of skin integrity loss, anatomical deformities, nail changes, and distal pulses when they screen diabetic patients. It is recommended to perform a careful foot examination at least annually in diabetic patients who are over the age of 15. Nevertheless, there are some risk stratification systems that can provide a better understanding of how often foot screenings should be performed based on each patient. These systems utilize factors such as peripheral arterial disease, impaired protective sensation of foot, anatomical deformities, history of previous foot ulcer or amputation, and the presence of other concurrent disorders. One of the IWGDF guidelines on the management and prevention of diabetic foot recommended a foot screening assessment sheet for physical examination in each screening. Physicians should educate patients to perform self foot examinations more often. There are diagnostic tools in order to perform a better screening such as the Semmes-Weinstein monofilament, a tuning fork, and a biothesiometer.

Diabetic foot is a known complication of diabetes. Diabetic patients who are at risk of foot ulceration develop diabetic foot, which may get infected later. The healing process of diabetic foot usually takes a long time (2-5 months) with proper treatment. The final state of diabetic foot is a necrotic foot. The wound healing process can get prolonged in patients with elevated body mass index or osteomyelitis. Diabetic foot ulcers can cause numerous complications, such as sepsis, osteomyelitis, gangrene, lower limb amputation, and death. The chance of amputation is increased with factors such as old age, peripheral vascular disease (PAD), transcutaneous oxygen reduction, poor glycemic control, being on dialysis, and osteomyelitis. If left untreated, prognosis could be very bad and it can eventually lead to death. Male gender, old age, peripheral vascular disease, and concurrent chronic renal failure are related to a higher rate of death. The presence of a single ulcer is associated with a particularly good prognosis among patients with diabetic foot, compared to multiple ulcers. Glycemic control improvement, treatment of neuropathy, and immediate treatment of ulcers improves the prognosis.

History of previous foot ulceration and poor glycemic control are two common positive histories in many patients suffering from diabetic foot. Other possible histories in a diabetic foot patient are nephropathy, retinopathy, neuropathy, previous amputation, trauma, and smoking. Diabetic foot patients may present to physicians with numerous symptoms. Nevertheless, the most common symptoms reported in these patients are burning, pins and needles sensation, discharge, and pain. In the late stages of ulcer infection, fever and rigor are also common.

Patients with a diabetic foot ulcer could appear ill if ulcers are severe or infected. In severe and chronic infected ulcers, patients may have fever, tachycardia, and low blood pressure. Neuromuscular examination of patients with diabetic foot is usually normal, except in their foot. Altered motor tone, reflexes, and sensation is expected in these patients. Neuropathy symptoms scores (NSS) and neuropathy disability scores (NDS) are helpful in neuropathy assessment of patients with diabetic foot. Findings such as impaired vibration and pressure perception, position sense, and abnormal thresholds for warm thermal perception favor the diagnosis of sensory neuropathy. It is critical to check the extremities for findings such as ulcers, peeling skin, dilated or varicose veins, shiny skin with reduced hair distribution, and broken nails while examining diabetic foot. Moreover, infection possibility should be evaluated. Findings such as pus, erythema, warmth, induration, and bad odor suggest the presence of infection. In some cases, unroofing a small scar demonstrates a deeper infected abscesses. In other words, evaluating an ulcer for infection must be done after debridement. Other necessary physical examinations in these patients are checking the capillary filling time, ankle brachial index, tactile and vibration sensation, and pressure perception.

Worsened glycemic control could be seen in the laboratory evaluation of diabetic foot patients. Even in the presence of infection, there is no guarantee that measures such as WBC, ESR, and CRP be elevated. For detection of the main responsible microorganisms, biopsy or, curettage or aspiration, of a tissue sample is recommended. It is recommended to obtain a sample from discharge of the ulcer‘s base. Moreover, due to the contamination of all ulcers, a culture from a non-infectious ulcer is not recommended. For confirming osteomyelitis diagnosis and for appropriate antibiotic treatment, it is critical to obtain a bone biopsy. Properly obtained specimens for a culture prior to initiating empiric therapy, provide useful information for guiding antibiotic selection, particularly in those with chronic or previously treated infections which are commonly caused by gram-negative bacilli or obligate anaerobic organisms.

There are no ECG findings associated with diabetic foot.

Although a plain X-ray is not successful in osteomyelitis diagnosis within the first weeks of involvement, it is recommended to be performed in any diabetic foot patients with a deep or enduring ulcer. X-rays of the diabetic foot can be helpful in detecting foreign bodies, gas, joint effusion, and osteolysis.

It is recommended to perform a CT scan only if an MRI is contraindicated. A CT scan is a sensitive modality for detecting abnormal bone appearance in patients with a diabetic foot ulceration. Altered appearance of bones such as bone erosions, charcot joint, reduced joint space, osteopenia, and osteophyte formation can be detected on a CT scan.

Magnetic resonance imaging (MRI) is specific for osteomyelitis diagnosis. This imaging modality has a 90% sensitivity and an 85% specificity in the diagnosis of diabetic foot ulcers. While an MRI is very efficient in the diagnosis of diabetic foot, its usage with contrast materials such as gadolinium is not recommended in diabetic patients with evidence of renal diseases. A magnetic resonance angiography (MRA) can be helpful in the evaluation of limb perfusion. Nevertheless, it has limited spatial resolution and reports could be influenced by previous stents or implants.

Colorful doppler ultrasound has an 89% and a 68% sensitivity for the iliac artery and the popliteal artery, respectfully. Nevertheless, its sensitivity is higher for anterior and posterior tibial arteries (90%). For a complete evaluation of lower limb perfusion all of the iliac, femoral, popliteal, and tibial arteries they should be scanned by a colorful doppler ultrasound. Doppler ultrasound is not accurate when there is considerable calcification.

A bone scan and a white blood cell scan are two imaging modalities that can be used to assist physicians to better diagnose diabetic foot ulcerations. Both could be used when there is a high clinical suspicion for osteomyelitis while plain X-rays are negative. A leukocyte or white blood cell scan has a higher specificity for ostemyelitis diagnosis and is accurate even in neuropathic patients, in contrast to the bone scan.

Transcutaneous oxygen pressure (TcPO2) measurements can provide data on the perfusion of the involved limb. Although, its accuracy is not totally accepted in presence of severe ischemia and edema. Transcutaneous oxygen pressure (TcPO2) that measures less than 30 mmHg represents the necessity of a complete treatment, due to a very low chance of a spontaneous wound healing. On the other hand, measures more than 40 mmHg predict an acceptable chance of a spontaneous wound healing.

Appropriate wound care is essential for the management of all diabetic foot ulcers. Uninfected diabetic ulcers do not require antibiotic therapy. On the contrary, for acutely infected wounds, empiric antibiotic therapy with coverage against Gram-positive cocci should be started right after obtaining a post-debridement specimen for aerobic and anaerobic cultures. Infections with antibiotic-resistant organisms, chronic or severe ulcers, or which have been previously treated usually require broader spectrum regimens. Treatment strategies are dependent on the ulcer‘s grade, presence of infection, and perfusion. For an effective treatment which lowers the chance of future diabetic foot ulcers, control of blood sugar, pressure off-loading, and treatment of other comorbidities are also critical. Aim of treatment should be focused on improving prognosis and decreasing complications such as amputation. In very severe ulcers, when the patient has history of previous MRSA infection or when there has been colonization within the past year in regions with high prevalence of MRSA infection, MRSA should also be covered by antibiotic treatments. For an ideal treatment, physicians should evaluate the severity of ulcers and possible risk factors of pseudomonas aeruginosa or extended-spectrum β-lactamase (ESBL)–producing organisms.

One of the centerpieces of diabetic foot treatment is debridement of necrotic and fibrotic tissues as well as calluses. Debridement should be done until it reaches the bleeding tissue, which is both a treatment and a diagnostic method to evaluate ulcer margin and abscess‘s presence.

Foot ulcers can be prevented by frequent physical examinations, proper glycemic control, good foot hygiene, diabetic socks and shoes, and by avoiding injury. Studies recommend annual screening by the physician for every diabetic patient older than 15 years old and more frequently for patients who are at risk (such as neuropathy). A careful examination should consist of a peripheral neuropathy assessment, which should be done by checking ankle reflexes, vibration, and sensation. A study showed the importance of using a 10-g Semmes-Weinstein monofilament with a 10 fold risk elevation of foot ulcer development and a 17 fold increase in amputation rate within a 32-month follow up in patients who had abnormal 10-g Semmes-Weinstein monofilament examinations.

For an appropriate secondary prevention, physicians should focus on strategies such as pressure offloading, appropriate footwear (such as pressure-relieving footwear), treatment of existing infection, and debridement. Early amputation and reconstruction of the damaged vessels could also assist in faster wound healing and will prevent further destruction.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Daniel A. Gerber, M.D. [2] Anahita Deylamsalehi, M.D.[3]

The discovery of the association between diabetes and foot ulceration and subsequent infection dates back to the 1850s. Significant breakthroughs in the management of diabetic foot wounds include the introduction of surgical debridement occurred in the early 1900s by Frederick Treves. He also introduced the critical role of footwear in diabetic foot ulcers. Furthermore the discovery of penicillin in 1928 by Alexander Fleming reduced the mortality rate of diabetic foot patients and their related complications significantly. Throughout the 20th century, advances in surgical limb revascularization and the advent of angioplasty drastically reduced the need for amputation. The latter method remained the mainstays of diabetic foot management, in the 2004 and 2012 Infectious Disease Society of America guidelines.

• Marchal de Calvi and Thomas Hodgkin first identified an association between diabetes and foot ulceration and potential infection of that, as a significant source of morbidity and mortality among these patients, in 1850s. All skin ulcers at that time were treated with prolonged bedrest, however these lesions didn’t response to immobilization.^[1][2]
• At the turn of the 19th century, Frederick Treves introduced surgical debridement of diabetic wounds as well as modified footwear in order to distribute pressure more evenly across the heal.^[2]
• A significant breakthrough occurred in 1928, when a Scottish scientist, Alexander Fleming discovered penicillin, which further reduced mortality and morbidity (such as major amputation) from diabetic foot infections by nearly 50%.^[1][2]
• Throughout the 20th century, advances in surgical limb revascularization and the advent of angioplasty drastically reduced the need for amputation and remained a mainstay of treatment.^[3][4]
• In 2004, the Infectious Disease Society of America published initial clinical practice guideline for the diagnosis and treatment of diabetic foot infection and with recent updates in 2012, provide an up-to-date diagnostic and therapeutic information to clinicians.^[5]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Daniel A. Gerber, M.D. [2] Anahita Deylamsalehi, M.D.[3]

Diabetic foot is classified based on ulcer‘s features in order to assist with clinical decision-making regarding the need for oral or parenteral antibiotics, outpatient management, hospitalization, and surgical intervention. There are multiple methods of classification for diabetic foot. One of them that has been published by The Infectious Disease Society of America (IDSA) in their 2004 guideline and mainly has been focused on the extent of infection and inflammation of the ulcer. In addition another similar classification system has been released by The International Working Group on the Diabetic Foot (IWGDF) in 2012. The aforementioned systems were externally validated in a longitudinal study to assess prognostic value, which demonstrated increased risk for amputation among patients with infections classified as severe. Another widely accepted diabetic foot ulcer classification is Wagner ulcer classification system, which uses some ulcer‘s features such as depth, in addition to presence of osteomyelitis or gangrene.

• Diabetic foot infections are classified according to the severity of involvement to assist with clinical decision-making regarding the need for oral or parenteral antibiotics, outpatient management, need for hospitalization, and surgical intervention.^[1]
• The Infectious Disease Society of America (IDSA) introduced a classification scheme for these infections in their 2004 guidelines, broadly categorized as mild, moderate, and severe infections based upon the extent of infection and inflammation.^[2]
• The International Working Group on the Diabetic Foot (IWGDF) published a similar classification system in 2012.^[3]
• The aforementioned systems were externally validated in a longitudinal study to assess prognostic value, which demonstrated increased risk for amputation among patients with infections classified as severe.^[4]

Clinical Manifestation PEDIS Grade IDSA Severity No symptoms or signs of infection 1 Uninfected Local infection involving only the skin and the subcutaneous tissue without involvement of deeper tissues and without signs of SIRS If erythema, must be >0.5 cm to ≤2 cm around the ulcer. Exclude other causes of an inflammatory response of the skin (eg, trauma, gout, acute charcot neuro-osteoarthropathy, fracture, thrombosis, venous stasis). 2 Mild Local infection with erythema >2 cm or involving structures deeper than skin and subcutaneous tissues (eg, abscess, osteomyelitis, septic arthritis, fasciitis) without signs of SIRS 3 Moderate Local infection with the signs of SIRS, as manifested by ≥2 of the following: Temperature >38 °C or <36 °C Heart rate >90 beats/min Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg White blood cell count >12,000 or <4,000 cells/μL or ≥10% immature (band) forms 4 Severe

• Another widely accepted diabetic foot ulcer classification is Wagner ulcer classification system, which uses some ulcer‘s features such as depth, in addition to presence of osteomyelitis or gangrene.^[5]
  • Unfortunately Wagner ulcer classification system does not address important factors such as ischemia and infection.
  • The following table is a summary of Wagner ulcer classification system:

Grade	Ulcer‘s Features
0	Not an obvious open lesion
1	Superficial ulcer with partial or full-thickness
2	Extension of ulcer to other structures such as tendon, ligament, joint capsule, or deep fascia (without abscesses or osteomyelitis)
3	Extension of ulcer to other structures such as tendon, ligament, joint capsule, or deep fascia with abscesses, osteomyelitis or septic arthritis
4	Presence of gangrene, but localized to forefoot or heel
5	Presence of extensive gangrene

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]Vishnu Vardhan Serla M.B.B.S. [3]

Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. Neuropathy, ischemia and trauma are three main pathogenesis of diabetic foot. Neuropathy is the most common and is the responsible element in more than 60% of diabetic foot cases. Factors such as high blood glucose, reactive oxygen species, insufficient oxygenation of the nerves, and inflammation leads to neuropathy development in diabetic patients and it gets worse with alcohol use and smoking. Neuropathy can involve motor, autonomic, or sensory nerves and is able to involve both large and small fibers. Motor nerve involvement can lead to some mechanical changes in the foot of a diabetic patient, which causes more plantar pressure and higher risk of callus formation. Each and every factor leads to a higher rate of skin breakdown and ulceration. Autonomic neuropathy leads to anhidrosis and impaired function of oil glands, subsequent skin dryness, higher chance of skin breakdown, and ulcer formation. Diabetic patients with sensory neuropathy are more prone to ulcer formation and related complications, since they don’t feel pain with ever-deepening ulcers. Ischemia is the second best known pathogenesis of diabetic foot that could occur due to a higher rate of lower limb atherosclerosis in diabetic patients, compared to the normal population. Diabetes related complications such as micro and macrovascular complications further intensify ischemia. Ischemic changes can be discovered by an impaired ankle brachial index (ABI). Trauma to the foot usually acts as a trigger for diabetic foot. A defective hypoxic response has been explained in diabetic foot, which is related to a transcription factor named hypoxia‐inducible factor‐1 (HIF‐1). Lower levels of HIF‐1 in biopsies of diabetic foot could be related to its role in wound healing. Some genetic associations (such as MAPK14 gene located on chromosome 6, decreased expression of certain cytokines and growth factors, and the HSPA1B genotype) have been explained in diabetic foot development. Charcot arthropathy, some psychosocial conditions, necrotizing fasciitis (NF), vitamin D deficiency, tinea pedis, onychomycosis, and diabetic retinopathy are associated conditions in diabetic foot. On gross pathology, the most common site of ulceration is on the soles of the feet, under the metatarsal head with various depths and possible anatomical deformities of the foot. In microscopic evaluations of the ulcers, evidence of necrosis, hyperkeratosis, fibrosis, inflammation, cellular debris, granulation tissue, and angiogenesis have been found.

• Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. There are numerous responsible pathogenesis, such as arterial abnormalities, diabetic neuropathy, delayed wound healing, and being more vulnerable to infection or gangrene of the foot. The key components of diabetic foot are neuropathy, ischemia, and trauma. ^[1]
• Only 10% of diabetic foot cases are exclusively due to ischemia, nevertheless, 90% of them are related to neuropathy (alone or in combination to ischemia).^[2]
• Components such as neuropathy and peripheral arterial disease can mask signs and symptoms of the local infection.^[3]
• Based on a study done on diabetic patients with foot ulcers, three components such as peripheral neuropathy, deformity, and trauma were responsible for pathogenesis of diabetic foot in 63% of cases.^[4]

• The most important cause of diabetic foot is neuropathy. Based on a study, more than 60% of cases of diabetic foot are due to neuropathy.^[5]
• It involves roughly more than half of the patients with diabetes who are older than 60 years old.
• Peripheral neuropathy is usually profound at the point where it leads to the formation of a foot ulcer.
• Some metabolic abnormalities are due to hyperglycemia which leads to ischemia of endoneurial microvessels. In a nutshell, these changes are most likely caused by a combination of the factors listed below:
  • High blood glucose
  • Reactive oxygen species
  • Vasculopathy
  • Insufficient oxygenation of the nerves
  • Presence of inflammation and autoimmunity due to diabetes
  • Genetic factors
  • Mechanical injury
  • Smoking
  • Alcohol abuse
• Generalized symmetric distal polyneuropathy is the most common and widely recognized form of diabetic neuropathy that leads to diabetic foot. It may be either motor, autonomic, or sensory, and can involve small fibers, large fibers, or both.
  • Motor nerve involvement:^[6][7]
    • Motor nerve involvement can lead to some mechanical changes in the foot of a diabetic patient due to loss of sufficient neural supply and alteration in the natural anatomy of the foot. These mechanical changes cause more plantar pressure and a higher risk of callus formation, which subsequently leads to a higher rate of skin breakdown.
    • Moreover, these anatomical changes usually result in wider and thicker feet, which no longer fit in the patient‘s regular shoes and cause more trauma.
    • Pathogenesis of some of these mechanical changes are listed below:
      • Deprivation of neural supply to the intrinsic muscles of the foot → Long flexor and extensor tendons imbalanced → Flexion of the foot → High-arched foot and claw-toe deformity
      • Toes hyperextension → Overriding of the metatarsal-phalangeal joints and downward displacement of metatarsal heads → Increased prominence of both
      • Toes hyperextension → Distal displacement of metatarsal fat pads → Altering the natural cushioning of these fat pads
  • Autonomic neuropathy:^[8]
    • Autonomic neuropathy leads to anhidrosis and impaired function of oil glands. The subsequent dryness of the skin results in a higher chance of skin breakdown, ulcer formation, and bacterial invasion.
    • Autonomic neuropathy also decreases the proper peripheral sympathetic vascular tone which can lead to higher blood flow and pressure in distal arteries. The aforementioned changes plus capillary basement membrane destruction leads to edema. Edema itself increases the risk of ulcer formation.
  • Sensory neuropathy:
    • Appropriate sensory system helps patients to notice the tiniest fissures or blisters on their skin. This early sensation makes it possible for patients to take care of these skin defects and prevent further complications.
    • Conversely, diabetic patients with sensory neuropathy are more prone to ulcer formation and related complications, since they don’t feel pain with their ever-deepening ulcers.

• Atherosclerosis:^[9][10]
  • Atherosclerosis of the lower limb is 2 to 3 times more common in diabetic patients, compared to the normal population.
  • Investigators reported that atherosclerosis in diabetic patients is more prominent in tibial and fibular arteries of the calf, and arteries of the foot are relatively spared.
  • It usually occurs due to inflammation and consequently leads to accumulation of the foam cells.
• Micro and macrovascular complications are one of the leading causes of diabetic complications. Microvascular complications cause skin damage, infection, and impaired wound healing.^[11]
• The vascular changes which are responsible for foot problems include stiff arteries due to calcification of the smooth muscle cells in the arterial wall (mediasclerosis). Consequently, the stiff arteries are unable to expand in response to systolic pressure, which can lead to the movement of plaques in calf arteries.^[12]
• Most of these changes are discovered by an impaired ankle brachial index (ABI).
  • The resting ABI is the ratio of the blood pressure in the lower limb to the blood pressure of the arms. It is calculated by dividing the systolic blood pressure of the ankle by the systolic blood pressure of the arm.
  • It is a non-invasive method to assess the lower extremty arterial system and to detect the presence of arterial occlusion disease.
• Even in the presence of neuropathic foot ulcers, the reason of non healing wounds could be due to impaired blood supply to the tissue, which could be further augmented by antihypertensive medications.^[13].

• Trauma to the foot is frequently the trigger of diabetic foot ulcer development, and repetitive trauma and pressure to the area prevent healing.^[14]
• Excessive plantar pressure is related to limited joint mobility and foot deformities (such as charcot foot and hammer toe). Limited joint mobility and abnormal foot biomechanisms have been associated to an increased risk of ulceration.^[13]
• Poor vision and sensory neuropathy further put diabetic patients at risk of foot ulceration, as they do not feel the pain, nor do they see the ulcer. Loss of balance can also make patients more susceptible to falls.^[13]

• A transcription factor named hypoxia‐inducible factor‐1 (HIF‐1), which becomes stable in hypoxia, functions as a oxygen homeostasis regulator.^[15]
• Since HIF‐1 helps cells to respond adequately to hypoxia (by regulating erythropoiesis, metabolic changes, angiogenesis, proliferation, migration, and cell survival), it plays a critical role in wound healing.^[16]
• In addition, hypoxia‐inducible factor‐1 is responsible for the expression of genes that are critical to facilitate wound healing, such as the GLUT1 and GLUT3, lactate dehydrogenase, genes responsible for proper mitochondrial function (such as phosphoinositide‐dependent kinase‐1), type I collagen, and fibronectin. ^[17]
• There are numerous studies that detected lower levels of HIF‐1 in biopsies of diabetic foot. ^[18][19][20]
• One of the known pathogenesis of destabilized hypoxia‐inducible factor‐1 is hyperglycemia. This destabilization in hyperglycaemic conditions has been explained by an increase in the tendency of HIF‐1 towards VHL‐dependent degradation. ^[21]

• Naturally growth factors and cytokines are two mediators involved in wound healing. It is crystal clear that any genetical changes that affect the aforementioned mediators can result in defective wound healing and higher chance of diabetic foot. The following are some known genetical changes:^{[22][23][24][25]}
  • A single nucleotide polymorphism (SNPs) is responsible in the variation of these growth factors and cytokines. The best known gene is MAPK14 located on chromosome 6.
  • Decreased expression of certain cytokines and growth factors (such as IGF-1, TGF‐β1, PDGF, EGF, Interleukin 8, and Angiopoietin‐2)
• The HSPA1B genotype, a member of the heat shock protein 70 (Hsp70) family, has been related to a higher chance of diabetic foot development, amputation, and elongated hospital stay.^[26]

Conditions associated with diabetic foot include:^{[27][28][29][30][31][32]}

• Charcot arthropathy
• Peripheral arterial disease
• Psychosocial conditions, such as depression
• Necrotizing fasciitis (NF)
• Vitamin D deficiency
• Fungal infections, such as tinea pedis and onychomycosis
• Other complications of diabetes mellitus, such as diabetic retinopathy and nephropathy
• Hypertension

• On gross pathology, the most common site of ulceration is on the soles of the feet, under the metatarsal head (particularly at the second metatarsal head).
• Depth of ulcers could be different, ranging from superficial wounds to the involvement of ligaments and tendons, joint capsule, or deep fascia
• There is a high chance of concurrent anatomical foot deformities, such as claw toe or charcot joint.
• Presence of infective features of a ulcer, such as erythema, swelling, and purulent and malodor discharge.
• Abscess
• Gangrene

The following list is a summary of the possible microscopic histopathological changes of diabetic foot:^[34][35][36]

• Skin necrosis
• Hyperkeratosis
• Fibrosis
• Inflammation
• Cellular debris
• Granulation tissue
• Biofilms formation, which resembles infection
• Angiogenesis, which represents proper wound healing

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

Conditions such as peripheral neuropathy and ischemia are two common causes of diabetic foot ulcer formation. Decreased sensation due to peripheral neuropathy increase the risk of trauma which is another known cause of ulcer formation. Microorganisms such as staphylococcus aureus, pseudomonas aeruginosa, proteus mirabilis, escherichia coli and bacteroides fragilis are responsible for diabetic foot ulcer infection.

Common causes of diabetic foot may include:^[1][2][3][4]

• Peripheral neuropathy
• Ischemia from peripheral vascular disease
• Poor glycemic control
• In the presence of diabetic foot infection, the following are the most common causes of infections:
  • Staphylococcus aureus
  • Pseudomonas aeruginosa
  • Proteus mirabilis
  • Bacteroides fragilis
  • Escherichia coli (It was the most common gram negative bacteria based on one study. )
• Trauma and burn

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

Diabetic foot must be differentiated from other diseases that cause foot ulceration, erythema, swelling and skin lesion, such as skin and soft-tissue infections, gas gangrene, cellulitis, deep venous thrombosis and inflammatory disorders.

• Diabetic foot must be differentiated from other diseases that cause foot ulceration, erythema, swelling and skin lesion, such as:^[1][2][3]
  • Skin and soft-tissue infections:
    • Gas gangrene
    • Cellulitis
    • Vibrio vulnificus infection
    • Aeromonas hydrophila infection
  • Trauma
  • Deep venous thrombosis
  • Inflammatory disorders:
    • Pyoderma gangrenosum
    • Necrobiosis lipoidica

• Below, find a list of differential diagnosis for diabetic foot:

Diseases	Symptoms							Signs	Gold standard Investigation to diagnose
	History	Onset	Pain	Fever	Laterality	Scrotal swelling	Symptoms of primary disease
Diabetic foot	*History of poor glycemic control *Trauma *Burn	Chronic	+ –	+ –	Unilateral	–	Since it is related to diabetes, symptoms such as polyuria, polydipsia and polyphagia could be seen.	*Shiny skin *Decreased hair distribution *Ulcer *Signs of infection *Foot deformities such as charcot foot and hammer toe	The diagnosis of diabetic foot could be done by clinical findings, nevertheless MRI is essential to exclude the osteomyelitis.
(Cellulitis-erysipelas-skin abscess)	Acute painful swelling Fever	Acute	+	+	Unilateral	–	–	Tenderness, hotness, and may be fluctuation if abscess formed. Lymphangitis in nearby lymph nodes. Toxemia and fever in severe cases. Cellulitis involves the deeper dermis and erysipelas involves the upper dermis.[4]	Usually it doesn’t need any laboratory tests to diagnose.[5] Blood cultures are warranted for patients in the following circumstances:[6] Systemic toxicity Extensive skin or soft tissue involvement Underlying comorbidities persistent cellulitis In patients with recurrent cellulitis, serologic testing for beta-hemolytic streptococci is a good diagnostic tool.[7]
Lymphatic filariasis	History of living in endemic area or travelling to it	Chronic	+	+	Bilateral	+	–	Hepatomegaly Lymphedema Elephantiasis Lymphangitis Hydrocele Scrotal elephantiasis Lymphadenopathies Rhonchi may be present in patients with Pulmonary tropical eosinophilia syndrome.	Preparing blood smears Thick smears Thick smears consist of a thick layer of dehemoglobinized (lysed) red blood cells (RBCs). Thick smears allow a more efficient detection of parasites (increased sensitivity). Thin smears consist of blood spread in a layer such that the thickness decrease. By the ultrasound, the following findings can be observed: Dilated lymphatic channels Living worms tend to be in motion which called “filarial dance” sign.
Chronic venous insufficiency	History of untreated varicose veins Painful bilateral lower limb swelling that increases with standing and decreases by rest and leg elevation.	Chronic	+	–	Bilateral	+ (If congenial)	–	Typical varicose veins Skin change distribution correlate with varicose veins sites in the medial side of ankle and leg Reduction of swelling with limb elevation.	Duplex ultrasound will demonstrate typical findings of venous valvular insufficiency
Acute deep venous thrombosis	History of prolonged recumbency Classic symptoms of DVT include acute unilateral swelling, pain, and erythema	Acute	+	–	Unilateral	–	May be associated with primary disease mandates recumbency for long duration	Dilated superficial veins Difference in calf diameter is twice as likely to have DVT(most impotant sign )[8] Calf pain on passive dorsiflexion of the foot (Homan’s sign) isn’t realiable sign.	Compression ultrasonography (CUS) with doppler is the diagnostic test of choice D-dimer level is used for unprobable cases
Lipedema	Family history especially in women; X-linked dominant or autosomal dominant condition.[9] Abnormal deposition of fat and edema and easy bruising.	Chronic	+	–	Bilateral	–	–	Tender with palpation Negative Semmer sign to differentiate from lymphedema.[10] Pinching the skin on the upper surface of the toes. If it is possible to grasp a thin fold of tissue then it is negative result. In a positive result, it is only possible to grasp a lump of tissue.	MRI offers strong qualitative and quantitative parameters in the diagnosis of lipedema [11]
Myxedema	History of untreated hypothyroidism. Infiltration of the skin with glycosaminoglycans with associated water retention.	Chronic	+	–	Bilateral	–	+ (hypothyroidism )	Pretibial myxedema	Thyroid function tests.
Other causes of generalized edema	History of chronic general condition (cardiac-liver-renal)	Chronic	–	–	Bilateral	–	+		According to the primary cause ( Echo- LFTs– RFT)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2] Vishnu Vardhan Serla M.B.B.S. [3] Usama Talib, BSc, MD [4]

The incidence of diabetic foot ulcer is approximately 1500 per 100,000 diabetic individuals world wide. Among the US veterans the incidence of active diabetic foot ulcers is approximately 500 per 100,000 individuals. On the other hand the incidence of active diabetic foot ulcers in United Kingdom has been estimated 220 per 100,000 individuals. Furthermore it’s prevalence has been reported 170 per 100,000 individuals among the United Kingdom population. The 5 year risk of mortality in diabetic patients with a foot ulcer is 2.5 times higher than diabetic individuals without a foot ulcer. Based on 2 studies with different follow up duration, mortality rate of diabetic foot has been estimated as 10% and 24% in 16 months and 5 years follow up, respectively. Based on a systematic review and metanalysis done on diabetes patients, diabetic foot was more common among older patients. White people develop diabetic peripheral neuropathy (which is a serious risk factor for diabetic foot) more frequently. In 1987, Borch-Johnsen et al. described a male preponderance for the development of severe microvascular complications and diabetic foot disease is not an exception to this rule. Highest prevelance of diabetic foot has been reported in North America. In contrast, Oceania has the lowest reported prevelance of diabetic foot.

• The incidence of diabetic foot ulcer is approximately 630 per 100,000 diabetic individuals world wide.^[1][2][3][4]
• According to an other estimate the incidence of diabetic foot ulcer is approximately 1500 per 100,000 individuals worldwide.^[5]
• The incidence of active diabetic foot ulcers in the US veterans is approximately 500 per 100,000 individuals.^[1][2][3][4]
• The incidence of active diabetic foot ulcers in United Kingdom is approximately 220 per 100,000 individuals.^[1][2]
• Based on another study, up to 25% of diabetic patients develop diabetic foot within their disease period.^[6]
• It is estimated that 2% to 3% of diabetic patients experience diabetic foot every year.^[7][8]
• Between 15 to 20 percent of diabetic patients in the United States will be hospitalized due to diabetic foot and it’s complications at one point in their life.^[9]

• The prevalence of active diabetic foot ulcers in United Kingdom is approximately 170 per 100,000 individuals.^[1][2]
• Based on a cohort study which studied 310 patients with type 2 diabetes, diabetic foot prevelance was found to be 18.1%.^[10]
• In a study done on a diabetic population in Ethiopia, prevalence of diabetic foot ulcer has been estimated 13.6% with a 95% confidence interval (9.3-17.2) among 279 diabetic patients who attend a diabetic clinic.^[11]
• Prevalence of diabetic foot have been reported 51.8% based on a community based cross-sectional study which evaluated 620 diabetic patients in rural areas of India.^[12]
• The following table is a summary of prevalence of diabetic foot globally and in different regions:^[3]

Region	Prevalence of diabetic foot	95% Confidence interval
Global	6.3%	5.4–7.3%
North America	13.0%	10.0–15.9%
Asia	5.5%	4.6–6.4%
Europe	5.1%	4.1–6.0%
Africa	7.2%	5.1–9.3%
Oceania	3.0%	0.9–5.0%

• The 5 year risk of mortality in diabetic patients with a foot ulcer is 2.5 times higher than diabetic individuals without a foot ulcer.^[1]
• Based on 2 studies with different follow up duration, mortality rate of diabetic foot has been estimated as 10% and 24% in 16 months and 5 years follow up, respectively.^[13][14]
• Another study done in Liverpool foot clinic reported 44% five year mortality in diabetic patients with a new foot ulcer.^[15]
• Based on a study done in Spain mortality has been reported 28 among 1000 patients per year and the main cause (31.2%) was cardiovascular disease.^[16] Another study done in England demonstrated the cardiovascular diseases as the main cause of death in diabetic foot patients as well.^[14]

Based on a systematic review and metanalysis done on diabetes patients, diabetic foot was more common among older patients.^[3][17]

White people develop diabetic peripheral neuropathy (which is a serious risk factor for diabetic foot) more frequently.^[18]

• In 1987, Borch-Johnsen et al. described a male preponderance for the development of severe microvascular complications and diabetic foot disease is not an exception to this rule.^{[19] [20]}
• For unknown reasons, men have a higher risk of diabetic foot disease compared to women.^[17][21]
• Few possible explanations could be the higher bioavailability of nitric oxide (NO), higher responsiveness to NO and the protective role of estrogen in women. ^[22]. However the beneficial effect of these factors could be reversed by diabetes itself and irrespective of the menopausal status of female patients.

• Highest prevelance of diabetic foot has been reported in North America.^[3]
• Lowest prevalence of diabetic foot has been reported in Oceania.
• Africa has higher prevalence of diabetic foot, compared to Asia and Europe.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

There are numerous risk factors for diabetic foot development in a diabetic patient, such as poor glycaemic control, inappropriate foot care and footwear, foot deformities, peripheral arterial disease, peripheral neuropathy, history of previous foot ulcer or amputation, infection, high body mass index, and poor socioeconomic status. Other comorbidities such as hypertension and dyslipidemia are also responsible risk factors for diabetic foot ulceration.

• Common risk factors in the development of diabetic foot include:^{[1][2][3][4][5][6][7][8][9][10][11]}
  • Poorly controlled diabetes mellitus (poor glycaemic control and high HbA1c)
  • Prolonged diabetes mellitus (more than 10 years)
  • Old age
  • Poor foot care
  • Male gender
  • Previous history of foot ulcer
  • Foot deformities
  • Peripheral arterial disease
  • High plantar pressure
  • Peripheral neuropathy
  • Impaired cutaneous oxygenation
  • History of previous amputation
  • Infection
  • Inappropriate footwears
  • Bare foot walking (as it is a cultural practice in some nations)
  • Poor socioeconomic status
  • Diastolic hypertension
  • Dyslipidemia
  • High body mass index (BMI)
  • Improper nail care
  • Burn
  • Smoking or tobacco chewing
  • Alcohol

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

The main focus of diabetic foot screening should be on peripheral neuropathy detection, since foot ulcer development is rare in the absence of neuropathy. In addition to examining the peripheral neuropathy, physicians should search for any evidence of skin integrity loss, anatomical deformities, nail changes and distal pulses when they screen diabetic patients. It is recommended to perform a careful foot examination at least annually in diabetic patients who are over the age of 15. Nevertheless, there are some risk stratification systems that can provide a better understanding of how often foot screening should be performed based on each patient. These systems utilize factors such as peripheral arterial disease, impaired protective sensation of foot, anatomical deformities, history of previous foot ulcer or amputation and presence of other concurrent disorders. One of the IWGDF guidelines on the management and prevention of diabetic foot recommends a foot screening assessment sheet for physical examination in each screening. Physicians should educate patients to perform self foot examinations more often. There are diagnostic tools in order to perform a better screening such as Semmes-Weinstein monofilament, tuning fork and biothesiometer.

• The main focus of diabetic foot screening should be on peripheral neuropathy detection, since foot ulcer development is rare in the absence of neuropathy. However, searching for other factors such as skin integrity, any wound or ulceration, anatomical deformities, nail changes and distal pulses should not be omitted during foot examination.^[1][2][3]
• A regular foot examination should be done in diabetic patients, in order to detect peripheral neuropathy, peripheral arterial disease and anatomical foot deformities.^[4]
• It is recommended to perform a careful foot examination at least annually in diabetic patients over the age of 15. Nevertheless, physicians should educate patients to perform self foot examinations more often.
• In diabetic patients who have higher risk of diabetic foot ulceration, more frequent (every 1-6 months) examinations and follow-up should be considered.
• An evidence‐based guideline published by the International Working Group on the diabetic foot (IWGDF) has demonstrated a risk stratification system for detecting diabetic patients with high risk of foot ulceration. The aforementioned guideline includes a scoring system which clarifies the proper intervals for screening diabetic patients. The following table is a summary of this system:^[5][6]

Characteristics	Score	Risk of ulcer development	Recommended screening frequency
Intact protective sensation of foot Absent of peripheral artery disease	0	Very low	Annually
Impaired protective sensation of foot OR Peripheral artery disease	1	Low	Every 6‐12 months
Impaired protective sensation of foot AND peripheral artery disease OR Impaired protective sensation of foot AND foot deformity OR Peripheral artery disease AND foot deformity	2	Moderate	Every 3‐6 months
Impaired protective sensation of foot OR peripheral artery disease AND at least one of the following: Previous history of a foot ulcer Previous history of amputation of a lower extremity End‐stage renal disease	3	High	Every 1‐3 months

• One of the IWGDF guidelines on the management and prevention of the diabetic foot, published in 2011, recommended a foot screening assessment sheet for physical examination in each screening. The following table depicts this assessment sheet:^[7]

Search for anatomical deformities or bony prominences

Check the skin integrity

Monofilament test

Tuning fork test

Cotton wool sensation test

Search for any evidences of pressure on foot, such as callus formation or discoloration

Examine joints and search for abnormal joint mobility

Check pulses, especially tibial posterior and dorsal pedal artery

Search for any evidence of previous ulcer and amputation

Evaluate footwears

• The following are some useful screening tools for diabetic foot screening:^{[8][9][10][11]}
  • Semmes-Weinstein monofilament
  • Tuning fork
  • Biothesiometer

[[Category:Up-to-date]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2] Vishnu Vardhan Serla M.B.B.S. [3] Usama Talib, BSc, MD [4]

Diabetic foot is a known complication of diabetes. Diabetic patients who are at risk of foot ulceration, develop diabetic foot which may get infected later. The healing process of diabetic foot usually takes a long time (2-5 months) with proper treatment. The final state of diabetic foot is a necrotic foot. The wound healing process can get prolonged in patients with high elevated body mass index or osteomyelitis. Diabetic foot ulcers can cause numerous complications, such as sepsis, osteomyelitis, gangrene, lower limb amputation, and death. The chance of amputation is increased with factors such as old age, peripheral vascular disease (PAD), transcutaneous oxygen reduction, poor glycemic control, being on dialysis, and osteomyelitis. If left untreated, prognosis could be very bad and it can eventually lead to death. Male gender, old age, peripheral vascular disease, and concurrent chronic renal failure are related to higher rate of death. The presence of a single ulcer is associated with a particularly good prognosis among patients with diabetic foot, compared to multiple ulcers. Glycemic control improvement, treatment of neuropathy, and immediate treatment of ulcers improve the prognosis.

• Diabetic foot is a known complication of diabetes and is more related to diabetes mellitus type 2, compared to type 1 diabetes.^[1][2]
• Diabetic foot ulcers heal slowly and it usually takes between 2-5 months to completely heal with proper treatment.^[3]
• Diabetic patients who are at risk of foot ulceration, develop diabetic foot which may get infected later. The final state of diabetic foot is a necrotic foot.^[4]
• Based on a study, factors such as elevated body mass index and osteomyelitis prolong the wound healing process.^[5]
• If left untreated, diabetic ulcers may progress to infection, sepsis, or osteomyelitis. According to an estimate, 20% of significant diabetic foot ulcers end up requiring an amputation.

• Diabetic foot ulcers can cause numerous complications including:^{[6][7][8][9][5][10][11][12]}
  • Infection:
    • Diabetic foot infection is the most common cause of hospitalization in diabetic patients.
  • Sepsis
  • Osteomyelitis:
    • The following features of a diabetic foot ulcer increase the chance of osteomyelitis development:
      • Ulcers larger than 2 centimeters
      • Ulcers that last more than 1 week
      • Ulcers with positive probe to bone test
  • Gangrene
  • Lower limb amputation
    • It is estimated that roughly half of non traumatic lower limb amputation is due to diabetic foot in North America and Europe.
    • The following factors increase the risk of amputation in diabetic foot patients:
      • Old age
      • Peripheral vascular disease (PAD)
      • Neuropathy
      • Transcutaneous oxygen reduction
      • Poor glycemic control
      • Osteomyelitis
      • Smoking
      • Dialysis
  • Death
    • Patients with diabetic foot have an increased risk of all-cause mortality, especially cardiovascular disorders, compared with diabetic patients without a history of diabetic foot ulcer.
    • The following risk factors have been associated with higher rate of mortality:
      • Old age
      • Male gender
      • Dialysis
      • Chronic renal failure
      • Peripheral vascular disease (PAD)
• Complications of diabetic foot have been more common in male patients and patients older than 60 years old.^[9]

• If left untreated, prognosis could be very bad and it can eventually lead to death.^[6]
• The 5 year risk of mortality in diabetic patients with a foot ulcer is 2.5 times higher than diabetic individuals without a foot ulcer.^[6][13]
• The 5-year survival rate in diabetic patients with lower limb ulcers is 43%, compared to non-diabetic patients with foot ulcer (56%).^[13]
• The following factors can determine the prognosis of diabetic foot:^[14]
  • Peripheral arterial disease
  • Edema
  • Infection
  • Presence of other comorbidities
• The presence of a single ulcer is associated with a particularly good prognosis among patients with diabetic foot, compared to multiple ulcers.^[15]
• Modification of specific risk factors (such as improving glycemic control, treatment of neuropathy, and immediate treatment of ulcers) improves the prognosis in a significant manner.^[16]
• Three year mortality has been estimated 35-50% after amputation of the diabetic foot.^[17]
• Based on different studies, toe pressure more than 55 mmHg is indicative for a better wound healing, and therefore, a better prognosis. In the contrary, toe pressure less than 30 mmHg in a diabetic patient with diabetic foot is indicative of a severely defective wound healing.^[18][19]