Diabetic foot ulcers, as shown in the images below, occur as a result of various factors, such as mechanical changes in conformation of the bony architecture of the foot, peripheral neuropathy, and atherosclerotic peripheral arterial disease, all of which occur with higher frequency and intensity in the diabetic population. [1, 2]
Nonenzymatic glycation predisposes ligaments to stiffness. Neuropathy causes loss of protective sensation and loss of coordination of muscle groups in the foot and leg, both of which increase mechanical stresses during ambulation.
Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes.  Diabetes is the leading cause of nontraumatic lower extremity amputations in the United States, with approximately 5% of diabetics developing foot ulcers each year and 1% requiring amputation.
Physical examination of the extremity having a diabetic ulcer can be divided into examination of the ulcer and the general condition of the extremity, assessment of the possibility of vascular insufficiency,  and assessment for the possibility of peripheral neuropathy.
The staging of diabetic foot wounds is based on the depth of soft tissue and osseous involvement. [5, 6, 7] A complete blood cell count should be done, along with assessment of serum glucose, glycohemoglobin, and creatinine levels.
The management of diabetic foot ulcers requires offloading the wound by using appropriate therapeutic footwear, [8, 9] daily saline or similar dressings to provide a moist wound environment,  debridement when necessary, antibiotic therapy if osteomyelitis or cellulitis is present, [11, 12] optimal control of blood glucose, and evaluation and correction of peripheral arterial insufficiency.
A vascular surgeon and/or podiatric surgeon should evaluate all patients with diabetic foot ulcers so as to determine the need for debridement, revisional surgery on bony architecture, vascular reconstruction, or soft tissue coverage.
The hemorrheologic agent cilostazol is contraindicated in patients with congestive heart failure. See Medication regarding the product's black box warning.
Atherosclerosis and peripheral neuropathy occur with increased frequency in persons with diabetes mellitus (DM).
Overall, people with diabetes mellitus (DM) have a higher incidence of atherosclerosis, thickening of capillary basement membranes, arteriolar hyalinosis, and endothelial proliferation. Calcification and thickening of the arterial media (Mönckeberg sclerosis) are also noted with higher frequency in the diabetic population, although whether these factors have any impact on the circulatory status is unclear.
Diabetic persons, like people who are not diabetic, may develop atherosclerotic disease of large-sized and medium-sized arteries, such as aortoiliac and femoropopliteal atherosclerosis. However, significant atherosclerotic disease of the infrapopliteal segments is particularly common in the diabetic population. Underlying digital artery disease, when compounded by an infected ulcer in close proximity, may result in complete loss of digital collaterals and precipitate gangrene.
The reason for the prevalence of this form of arterial disease in diabetic persons is thought to result from a number of metabolic abnormalities, including high low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) levels, elevated plasma von Willebrand factor, inhibition of prostacyclin synthesis, elevated plasma fibrinogen levels, and increased platelet adhesiveness.
Diabetic peripheral neuropathy
The pathophysiology of diabetic peripheral neuropathy is multifactorial and is thought to result from vascular disease occluding the vasa nervorum; endothelial dysfunction; deficiency of myoinositol-altering myelin synthesis and diminishing sodium-potassium adenine triphosphatase (ATPase) activity; chronic hyperosmolarity, causing edema of nerve trunks; and effects of increased sorbitol and fructose. 
The result of loss of sensation in the foot is repetitive stress; unnoticed injuries and fractures; structural foot deformity, such as hammertoes, bunions, metatarsal deformities, or Charcot foot (see the image below), as depicted in the image below; further stress; and eventual tissue breakdown. Unnoticed excessive heat or cold, pressure from a poorly fitting shoe, or damage from a blunt or sharp object inadvertently left in the shoe may cause blistering and ulceration. These factors, combined with poor arterial inflow, confer a high risk of limb loss on the patient with diabetes.
See Diabetic Neuropathy for more information.
The etiologies of diabetic ulceration include neuropathy,  arterial disease,  pressure,  and foot deformity.  Diabetic peripheral neuropathy, present in 60% of diabetic persons and 80% of diabetic persons with foot ulcers, confers the greatest risk of foot ulceration; microvascular disease and suboptimal glycemic control contribute.
A study by Naemi et al indicated that tissue mechanics may be associated with foot ulceration in patients with diabetic neuropathy, with an evaluation of 39 patients finding that the heel pad in nonulcerated feet tended to be stiffer than in ulcerated feet.  . These results were further elucidated in another study by Naemi et al, which reported that the risk of diabetic foot ulcer is higher in diabetic neuropathy patients who have greater plantar soft tissue thickness and lower stiffness in the area of the first metatarsal head. The investigators found that adding the mechanical properties of plantar soft tissue (stiffness and thickness) to commonly evaluated clinical parameters improved specificity, sensitivity, prediction accuracy, and prognosis strength by 3%, 14%, 5%, and 1%, respectively. 
The anatomy of the foot must be considered in risk calculation. A person with flatfoot is more likely to have disproportionate stress across the foot and may have an increased risk for tissue inflammation in high-stress regions.
Sensory neuropathy involving the feet may lead to unrecognized episodes of trauma due to ill-fitting shoes. Motor neuropathy, causing intrinsic muscle weakness and splaying of the foot on weight bearing, compounds this trauma. The result is a convex foot with a rocker-bottom appearance. Multiple fractures are unnoticed until bone and joint deformities become marked. This is termed a Charcot foot (neuropathic osteoarthropathy) and most commonly is observed in diabetes mellitus, affecting about 2% of diabetic persons.
If a Charcot foot is neglected, ulceration may occur at pressure points, particularly the medial aspect of the navicular bone and the inferior aspect of the cuboid bone. Sinus tracts progress from the ulcerations into the deeper planes of the foot and into the bone. Charcot change can also affect the ankle, causing displacement of the ankle mortise and ulceration, which can lead to the need for amputation.
According to the National Institute of Diabetes and Digestive and Kidney Diseases, an estimated 16 million Americans are known to have diabetes, and millions more are considered to be at risk for developing the disease. Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes.  Among patients with diabetes, 15% develop a foot ulcer, and 12-24% of individuals with a foot ulcer require amputation. Indeed, diabetes is the leading cause of nontraumatic lower extremity amputations in the United States. In fact, every year approximately 5% of diabetics develop foot ulcers and 1% require amputation.
Age distribution for diabetic ulcers
Diabetes occurs in 3-6% of Americans. Of these, 10% have type 1 diabetes and are usually diagnosed when they are younger than 40 years. Among Medicare-aged adults, the prevalence of diabetes is about 10% (of these, 90% have type 2 diabetes). Diabetic neuropathy tends to occur about 10 years after the onset of diabetes, and, therefore, diabetic foot deformity and ulceration occur sometime thereafter.
Prevalence of diabetic ulcers by race
The issue of diabetic foot disease is of particular concern in the Latino communities of the Eastern United States, in African Americans,  and in Native Americans, who tend to have the highest prevalence of diabetes in the world.
See Diabetic Foot Infections for more information.
Mortality in people with diabetes and foot ulcers is often the result of associated large vessel arteriosclerotic disease involving the coronary or renal arteries.
Limb loss is a significant risk in patients with diabetic foot ulcers, particularly if treatment has been delayed.  Diabetes is the predominant etiology for nontraumatic lower extremity amputations in the United States. Half of all nontraumatic amputations are a result of diabetic foot complications, and the 5-year risk of needing a contralateral amputation is 50%. 
In diabetic people with neuropathy,  even if successful management results in healing of the foot ulcer, the recurrence rate is 66% and the amputation rate rises to 12%.
A study by Chammas et al indicated that ischemic heart disease is the primary cause of premature death in patients with diabetic foot ulcer, finding it to be the major source of mortality on postmortem examination in 62.5% of 243 diabetic foot ulcer patients. The study also found that in patients with diabetic foot ulcer, the mean age of death from ischemic heart disease, as derived from postmortem examination, was 5 years below that of controls. Patients with neuropathic foot ulcers were determined to have the highest risk of premature death from ischemic heart disease. 
A study by Chen et al indicated that following hospital treatment for diabetic foot ulcer, invasive systemic infection associated with the ulcer (DFU-ISI) is an important late complication that increases mortality risk. In the study’s patients, methicillin-resistant Staphylococcus aureus (MRSA) gave rise to 57% of the ISIs. Using Cox regression modeling, the investigators found that complicated ulcer healing and the presence of MRSA in the initial ulcer culture predicted the development of DFU-ISIs (hazard ratios of 3.812 and 2.030, respectively), with the hazard ratio for mortality risk in association with DFU-ISIs being 1.987. 
The risk of foot ulceration and limb amputation in people with diabetes is lessened by patient education stressing the importance of routine preventive podiatric care, appropriate shoes, avoidance of cigarette smoking, control of hyperlipidemia, and adequate glycemic control. For excellent patient education resources, visit eMedicineHealth’s Diabetes Center. Also, see eMedicineHealth’s patient education article Diabetic Foot Care.
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- Approach Considerations
- Management of Systemic and Local Factors
- Wound and Foot Care
- Surgical Care
- Options for Soft Tissue Coverage of the Clean But Nonhealing Wound
- Hyperbaric Oxygen Treatment
- Dietary Chages
- Restriction of Activity
- Measures for Prevention of Diabetic Ulcers
- Long-Term Monitoring
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