Diabetic Foot Ulcer Neuropathy, impaired vasculature, and immune responses

Abstract

Diabetic foot ulcers (DFUs) are a debilitating complication frequently observed in long-term diabetes patients. These ulcers are categorized into neuropathic, ischemic, and neuroischemic, with neuroischemia being the most prevalent. Subclinical inflammation plays a vital role in the development of diabetes complications, contributing to the severity of foot ulcers. Peripheral vascular disease and neuropathy are significant predisposing factors for DFUs. This chapter delves into the pathogenesis of DFUs, focusing on three key elements: neuropathy, impaired vasculature, and immune responses. Neuropathy in diabetes is induced by metabolic disruptions, such as hyperglycemia and advanced glycation end products (AGEs), resulting in structural and functional nerve impairments. It diminishes pain perception, increasing the risk of unnoticed injuries. Impaired vasculature, particularly atherosclerosis, plays a pivotal role in diabetic vascular complications. PKC, hyperactive metabolic pathways, and oxidative stress disrupt vascular function and contribute to atherosclerosis development, directly impacting the risk of DFUs. Immune responses within DFUs involve impaired macrophages, neutrophils, keratinocytes, and fibroblasts, which collectively hinder the healing process. Additionally, elevated glucose levels negatively affect endothelial cells, angiogenesis, and stem cells, further delaying wound repair. Understanding these intricate mechanisms is essential in developing effective interventions for preventing and treating DFUs in diabetes.