[1] A key feature of wound healing is stepwise repair of lost extracellular matrix (ECM), the largest component of the dermal skin layer.

[5] Risk factors implicated in the development of diabetic foot ulcers are infection, older age,[6] diabetic neuropathy,[7] peripheral vascular disease, cigarette smoking, poor glycemic control, previous foot ulcerations[7] or amputations,[5] and ischemia of small and large blood vessels.

Peripheral neuropathy causes loss of pain or feeling in the toes, feet, legs, and arms due to distal nerve damage and low blood flow.

Blisters and sores may appear on numb areas of the feet and legs, such as metatarsophalangeal joints and the heel region, as a result of pressure or injury which may go unnoticed and eventually become a portal of entry for bacteria and infection.

[citation needed] Extra cellular matrix (or "ECM") is the external structural framework that cells attach to in multicellular organisms.

The specific species of ECM of connective tissues often differ chemically, but collagen generally forms the bulk of the structure.

[citation needed] The cells break down damaged ECM and replace it, generally increasing in number to react to the harm.

[15][16] Wound healing phases especially, granulation, re-epithelization and remodelling exhibit controlled turnover of extracellular matrix components.

[17] Increased glucose levels in the body end up in uncontrolled covalent bonding of aldose sugars to a protein or lipid without any normal glycosylation enzymes.

AGEs alter the properties of matrix proteins such as collagen, vitronectin, and laminin through AGE-AGE intermolecular covalent bonds or cross-linking.

[18] Complications in the diabetic foot and foot-ankle complex are wider and more destructive than expected and may compromise the structure and function of several systems: vascular, nervous, somatosensory, musculoskeletal.

Signs of infection require to be considered such as development of grey or yellow tissue, purulent discharge, unpleasant smell, sinus, undermined edges and exposure of bone or tendon.

[citation needed] A common method for this is using a special thermometer to look for spots on the foot that have higher temperature which indicate the possibility of an ulcer developing.

[50] The current guideline in the United Kingdom recommends collecting 8-10 pieces of information for predicting the development of foot ulcers.

[51] A simpler method proposed by researchers provides a more detailed risk score based on three pieces of information (insensitivity, foot pulse, previous history of ulcers or amputation).

[49][52] Diabetic shoes, insoles and socks are personalised products that relieve pressure on the foot in order to prevent ulcers.

[67] Biologically active bandages that combine hydrogel and hydrocolloid traits are available, however more research needs to be conducted as to the efficacy of this option over others.

[71] TCC also keeps the ankle from rotating during walking, which helps prevent shearing and twisting forces that can further damage the wound.

[72] Effective off loading is a key treatment modality for DFUs, particularly those where there is damage to the nerves in the feet (peripheral neuropathy).

[77] In 2015, a Cochrane review concluded that for people with diabetic foot ulcers, hyperbaric oxygen therapy reduced the risk of amputation and may improve the healing at 6 weeks.

[78] This treatment uses vacuum to remove excess fluid and cellular waste that usually prolong the inflammatory phase of wound healing.

[83] Phototherapy - there is very weak evidence to suggest that people with foot ulcers due to diabetes may have improved healing.

[84] There is no evidence to suggest that phototherapy improves the quality of life for people with foot ulcers caused by diabetes.

[84] Sucrose-octasulfate impregnated dressing is recommended by the International Working Group on the Diabetic Foot Ulcer (IWGDF)[85] for the treatment of non-infected, neuro-ischaemic diabetic foot ulcers that do not show an improvement with a standard of care regimen[86] Autologous combined leucocyte, platelet and fibrin as an adjunctive treatment, in addition to best standard of care is also recommended by IWGDF[87] However, there is only low quality evidence that such treatment is effective in treating diabetic foot ulcer.

[88] There is limited evidence that granulocyte colony-stimulating factor may not hasten the resolution of diabetic foot ulcer infection.

[90] A 2020 Cochrane systematic review evaluated the effects of nutritional supplements or special diets on healing foot ulcers in people with diabetes.

The review authors concluded that it's uncertain whether or not nutritional interventions have an effect on foot ulcer healing and that more research is needed to answer this question.

[92] A 2021 systematic review concluded that there was no strong evidence about the effects of psychological therapies on diabetic foot ulcer healing and recurrence.

In the United States; Black people, Native Americans, Hispanics and those living in rural areas or those with a lower socioeconomic status have an increased rate of amputations due to diabetic foot ulcers.