J Yeungnam Med Sci.  2023 Oct;40(4):328-334. 10.12701/jyms.2023.00731.

The pathophysiology of diabetic foot: a narrative review

• Kim J

• KMID: 2547355
• DOI: http://doi.org/10.12701/jyms.2023.00731

Abstract

An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.

Keyword

Angiopathy; Diabetic foot; Immune dysfunction; Metabolism; Neuropathy

Figure

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  Fig. 1. Diagram of pathophysiological factors in diabetic foot. The interaction of metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and diabetic angiopathy promotes the development and progression of diabetic foot infections and may lead to diabetic neuroarthropathy.

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  Fig. 2. Pathological pathways in the progression of diabetic foot. A schematic diagram representing the pathophysiology of DFUs via different pathological pathways. Endothelial dysfunction, ischemia, neuroarthropathy, and impaired immunology contribute to the pathophysiology of DFUs. ATP, adenosine triphosphate; PKC, protein kinase C; ROS, reactive oxygen species; DFU, diabetic foot ulcer.

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  Fig. 3. The process from callus formation to ulceration formation in patients with diabetes. The interaction of sensory, motor, and autonomic neuropathy can form a callus in the foot. After repeated exposure to external or minor trauma, skin ulcers form through subcutaneous hemorrhages. Adapted from Armstrong et al. [40] with permission of the New England Journal of Medicine.

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  Fig. 4. Development of diabetic foot ulcers due to diabetic neuropathy. The interplay of metabolic factors, immunopathy, diabetic neuropathy, and diabetic angiopathy fosters the development and progression of infections, ischemic ulcers, or gangrene in individuals with diabetes. Adapted from Schaper et al. [47] with permission from John Wiley & Sons, Ltd.

Reference

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