Diabetes can lead to distal symmetrical polyneuropathy (DSPN) that typically involves the feet first; and then progresses up the leg. DSPN can give rise to paresthesia, dysesthesia, allodynia, or neuropathic pain; and it increases the risk of ulcers, and bone or joint deformities. Persistent hyperglycemia leads to metabolic changes in the blood vessels that supply the peripheral nerves, causing the loss of nerve fibers. This is believed to be due to disorders of glial cell activation, ion channel expression, and central pain mechanisms.

Patients may present with foot deformities such as hammertoes, flat foot, equinus or varus deformities, etc.. Patients may also present with Charcot’s arthropathy. This is due to abnormal walking dynamics, pressure distribution, and trauma caused by muscle wasting and atrophy, combined with the loss of sensation.

PAD can present with intermittent claudication, acute ischemia, and tissue loss due to ulceration or gangrene. Patients are at increased risk of of infection and lower limb amputation. Reversible ischemia presents as claudication—i.e., cramping and aching pains in the muscles of the calves, thighs, or buttocks that are are aggravated by walking and alleviated by rest. Irreversible ischemia may present with the 6 P's—pain, pulselessness, paralysis, pallor, paresthesia, and poikilothermia.