Type 1 and type 2 DM represent similar processes of chronic, uncontrolled blood sugar, affecting multiple organs throughout the body, including the largest organ, the dermis. DM affects more than 30 million Americans. Lower
extremity complications such as diabetic foot ulcers are reported with a per-patient annual incidence of 2.2%, with 58% of presenting ulcers eventually acquiring a superimposed infection.¹ Once an infection occurs, the patient with DM frequently requires repeat hospitalizations with medical and surgical management and common progression to one or more amputations involving part of or the entire distal extremity. Twenty percent of all diabetic-related hospital admissions in the United States have been linked to an ulcer complicated by infection.² Furthermore, lower extremity amputations due to diabetes comprise more than 60% of nontraumatic lower extremely amputations.²

The pathophysiology of DM involves multiple risk factors that together lead to compromise of the neurological, vascular, and immunological systems.³ Diabetic neuropathy manifests in many forms affecting motor, autonomic, and sensory nerves throughout the body. An estimated two-thirds of diabetics have some form of neuropathy, accounting for those who manifest with symptoms and those whose symptoms are subclinical.⁴ Peripheral neuropathy prevents patients from recognizing painful sensations in areas, such as the foot, delaying the timeline in seeking care for these traumas. Continuous trauma without recognition lends to the increasing skin damage which breaks the protective barrier against infections.¹ Autonomic neuropathy causes dysfunctional blood flow mechanics, resulting in less perfusion and temperature regulation, especially in peripheral limbs. This loss generates a dry and unstable skin barrier that is more susceptible to fissures.³ Chronically fissured skin results in elevated risk of developing infection. Finally, uncontrolled hyperglycemia can directly weaken both the innate and adaptive immune systems through impairing leukocyte phagocytosis and chemotaxis.²

Vascular disturbances such as angiopathies, peripheral vascular disease, vasculitis, impaired venous return, and large-vessel stenosis may cause compromised blood flow to the feet, increasing risk for poor wound healing and infection. In diabetic patients, a chronic hyperglycemic state causes multicellular dysfunction within the vascular endothelium, specifically inhibiting the production of nitric oxide and preventing physiologic vasodilation of small vessels and arterioles.⁵ This microvascular compromise leads to the development of peripheral artery disease associated with DM, and subsequently, to the increased rates of skin breakdown, infection, and poor wound healing seen in this disease process. Similarly, large-vessel stenosis due to atherosclerosis or other pathologic causes can limit distal perfusion, resulting in chronic ischemic changes.

Although a majority of individuals with peripheral neuropathy are diabetics, neuropathy may be caused by many other conditions. These include syphilis, human immunodeficiency virus (HIV), hepatitis C, leprosy, alcohol abuse, vitamin B₁₂ deficiency, Charcot foot, and arsenic poisoning. Congenital defects that affect the spinal cord such as cerebral palsy and spinal bifida impact neuromuscular development and are often associated with varying degrees of peripheral neuropathy.⁶ Any form of inherited or developed neuropathy to the feet can prevent the patient from recognizing and avoiding injury to the extremity. Repetitive, unnoticed trauma increases risk of foot ulcers and subsequent foot infections.²