From the Guidelines
Diabetic foot ulcers are primarily caused by a combination of peripheral neuropathy, peripheral arterial disease, and repetitive stress or trauma, leading to a break in the skin and subsequent infection.
Pathophysiology of Diabetic Foot Ulcers
The development of diabetic foot ulcers is a complex process involving multiple factors, including:
- Peripheral neuropathy: Damage to the nerves in the feet, leading to loss of sensation, which can cause patients to be unaware of minor injuries or trauma, allowing them to progress into more severe ulcers 1, 2, 3.
- Peripheral arterial disease: Reduced blood flow to the feet, which can impair wound healing and increase the risk of infection 1, 3.
- Repetitive stress or trauma: Minor injuries, such as cuts or blisters, can become infected and progress into ulcers if not properly managed 1, 2, 3.
- Immunological perturbations: Diabetes can cause changes in the immune system, making it more difficult for the body to fight off infections 4, 1.
Key Factors Contributing to Ulcer Development
The following factors can contribute to the development of diabetic foot ulcers:
- Foot deformities: Abnormalities in the shape of the foot, such as hammertoes or bunions, can increase pressure on certain areas of the foot, leading to ulceration 2, 3.
- Limited joint mobility: Reduced mobility in the joints of the foot can lead to abnormal biomechanical loading, increasing pressure on certain areas and contributing to ulcer development 2, 3.
- High pressure areas: Areas of high pressure on the foot, such as the heel or ball of the foot, are more prone to ulceration 2, 3.
Infection and Complications
Infection is a common complication of diabetic foot ulcers, and can lead to more severe consequences, such as:
- Osteomyelitis: Infection of the bone, which can be difficult to treat and may require amputation 4, 1.
- Amputation: In severe cases, diabetic foot ulcers can lead to amputation of the affected limb 4, 1. Early recognition and treatment of diabetic foot ulcers are crucial to preventing these complications and promoting healing 1, 5.
From the Research
Pathophysiology of Diabetic Foot Ulcers
The pathophysiology of diabetic foot ulcers (DFUs) is complex and involves multiple biological mechanisms. Key factors contributing to the development of DFUs include:
- Hyperglycemia 6
- Chronic inflammation 6, 7
- Micro- and macro-circulatory dysfunction 6, 8
- Hypoxia 6
- Autonomic and sensory neuropathy 6, 9, 8
- Impaired neuropeptide signaling 6
Biological Mechanisms
The wound healing process in diabetes is impaired, involving:
- Disruption of the four phases of wound healing: hemostasis, inflammation, proliferative, and remodeling 6
- Alterations in cellular mechanisms, including immune cells, endothelial cells, keratinocytes, and fibroblasts 7
- Upregulation or downregulation of molecular signaling pathways 7
- Epigenetic regulatory mechanisms 7
Treatment Strategies
Current treatment approaches for DFUs focus on:
- Wound debridement, pressure off-loading, revascularization, and infection management 6, 10, 9
- Adjunctive therapies, such as bioengineered skin substitutes, extracellular matrix proteins, growth factors, and negative pressure wound therapy 6, 10
- Emerging treatment options, including stem cell-based therapies, gene therapy, and topical oxygen therapy 6, 10