As such, individuals who develop foot ulcers have a greatly decreased quality of life and have to rely on a great number of expensive healthcare resources. It is important to note that peripheral neuropathy (loss of sensation) affects sensory, motor, and autonomic nerve pathways, i.e. all types of nerves. This means that patients do not feel the early warning signs of pain or pressure from footwear or from infection. Thus, the primary risk factor for the development of ulcers is a loss of protective sensation by the patient. Further complications are that lowered white blood cell functioning and the presence of peripheral vascular disease allow wounds to become contaminated and infected by bacteria or fungi which are normally non-pathogenic in healthy individuals.

Loss of sensation and bone disease can produce boney deformities, which, combined with the loss of protective sensation, can produce skin ulceration from pressure or abrasions. In addition, patients can develop bunions, claw-toe, and hammer-toe deformities due to muscle imbalances. They lose normal blood vessel tone and thermal regulation, and have tissue swelling which can lead to ulceration and infection, while such skin also easily develops cracks, which are breeding grounds for harmful bacteria.

Blood vessel disease is another risk factor for patients with diabetes, leading also to diabetic foot ulceration and infection.

Another risk factor is related to the immune deficiency seen in diabetic patients. Immune components become less efficient, and white blood cells do not perform adequately, leaving these patients prone to infection from organisms that would not affect a healthy host. All of these complications means that the diabetic patient is highly susceptible to wounding that can lead to a break in the skin, which can initiate a foot infection that cannot be resolved easily, leading to the onset of chronic wounds and, eventually, amputation. Pressure over bony prominences is known to cause skin breakdown in patients with diabetes. In addition, due to leg and foot selling, shoes become tight due to swelling, thus increasing the direct pressure and shear forces applied to skin overlying bony prominences. Thickened nails increase pressure on the soft tissues surrounding the nails. This results in wounding and ulcer formation, and such nails are also prone to fungal infection.