A review of the basic science of the diabetic foot and its complications

Diabetes mellitus (DM) is a chronic metabolic disorder of impaired glucose metabolism, leading to widespread systemic complications. Among these, diabetic foot pathology contributes to severe morbidity. This review explores the underlying mechanisms of diabetic foot complications, including diabetic neuropathy, diabetic foot ulcer (DFU), infection, impaired wound healing, fracture healing, and Charcot neuroarthropathy (CNA). Diabetic neuropathy contributes to loss of protective sensation, balance impairment, ulcer formation, and an increased risk of lower limb amputations. DFUs arise from synergistic ischemia, neuropathy, and infection, often progressing to chronic wounds with poor healing capacity. Infections in diabetic feet are frequently caused by Staphylococcus aureus and other pathogens, often leading to severe complications, including osteomyelitis and amputations. Diabetes adversely affects bone health, resulting in delayed fracture healing through disrupted osteoblast activity, chronic inflammation, and oxidative stress. CNA remains a challenging condition, characterized by excessive local inflammation, bone resorption, and progressive joint destruction, leading to deformity and ulceration. Currently, management of diabetic foot complications is preventative, including glycaemic control, pressure offloading, infection management, and surgical interventions when necessary. Despite advancements in understanding pathology, there remain significant gaps in treatment strategies, necessitating further research into targeted therapies to mitigate neuropathy, enhance wound healing, and preserve limb function.