Hyaluronic acid, a pure glycosaminoglycan component, is found in high amounts in damaged or growing tissues. It stimulates cytokine production by macrophages and thus promotes angiogenesis. In normal skin chondroitin sulfate proteoglycan is mainly found in the basement membrane, but in healing wounds they are up-regulated throughout the granulation tissue especially during the second week of wound repair where they provide a temporary matrix with highly hydrative capacity. Binding of growth factors is clearly an important role of perlecan in wound healing and angiogenesis. Poor wound healing in diabetes mellitus may be related to perlecan expression. High levels of glucose can decrease perlecan expression in some cells, probably through transcriptional and post-transcriptional modification. Wound healing phases especially, granulation, re-epithelization and remodelling exhibit controlled turnover of extracellular matrix components. Altered metabolism
Diabetes mellitus is a metabolic disorder and hence the defects observed in diabetic wound healing are thought to be the result of altered protein and lipid metabolism and thereby abnormal granulation tissue formation. 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. These stable products then accumulate over the surface of cell membranes, structural proteins and circulating proteins. These products are called advanced glycation endproducts (AGEs) or Amadori products. Formation of AGEs occurs on extracellular matrix proteins with slow turnover rate. AGEs alter the properties of matrix proteins such as collagen, vitronectin, and laminin through AGE-AGE intermolecular covalent bonds or cross-linking.
However, it may reduce the need for surgical interventions such as amputations and hospitalizations.It is unknown that whether intensive or conventional blood glucose control is better for diabetic foot ulcer healing.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 its uncertain whether or not nutritional interventions have an effect on foot ulcer healing and that more research is needed to answer this question.Skin grafting and tissue replacements can help to improve the healing of diabetic foot ulcer.A 2021 systematic review concluded that there was no strong evidence about the effects of psychological therapies on diabetic foot ulcer healing and recurrence. Epidemiology
Approximately 15 percent of people with diabetes experience foot ulcers, and approximately 84 percent of lower limb amputations have a history of ulceration with only approximately half of amputees surviving for more than 2 years. 56 percent of individuals with foot ulcers who do not have an amputations survive for 5 years. Foot ulcers and amputations significantly reduce the quality of life. Approximately 8.8 percent of hospital admissions of diabetic patients are for foot related problems, and such hospital admissions are about 13 days longer than for diabetics without foot related admissions. Approximately 35 to 40 percent of ulcers recur within 3 years and up to 70 percent recur within 5 years. Diabetic foot disease is the leading cause of non-traumatic lower limb amputations. Research
Stem cell therapy may represent a treatment for promoting healing of diabetic foot ulcers.