Diabetic Neuropathic Foot Ulcers

Diabetic neuropathic foot ulcers are a complex and debilitating complication of diabetes mellitus, contributing significantly to patient morbidity, infection risk, and lower-limb amputation rates. 

Neuropathy-induced loss of protective sensation (LOPS), combined with peripheral arterial disease (PAD), biomechanical stress, and poor glycemic control, predisposes patients with diabetes to skin breakdown and infection. Once ulceration occurs, delayed detection—often due to sensory loss—can rapidly lead to tissue necrosis and systemic infection.

For clinicians, timely recognition, risk stratification, and management of diabetic neuropathic foot ulcers are essential to prevent progression to limb-threatening disease. This article provides a comprehensive, evidence-based overview of the risk factors, etiology, clinical presentation, treatment strategies, and preventive approaches to improve outcomes in patients with diabetic neuropathic foot ulcers.

Risk Factors for Diabetic Neuropathic Foot Ulcers

Several factors predispose patients with diabetes to neuropathic foot ulceration:

Peripheral neuropathy. When a patient has sensory neuropathy they can experience LOPS, preventing them from detecting trauma.¹ This can lead to delays in diagnosis or treatment, potentially negatively influencing outcomes.

Foot deformities and biomechanical abnormalities. Claw toes, prominent metatarsal heads, and limited joint mobility, for example, lead to abnormal plantar pressure distribution and increased callus formation.

PAD. Peripheral arterial disease, which impairs wound healing and increases the risk of amputation, is a contributing factor in 50–70% of diabetic foot ulcers.²

Previous foot ulceration or amputation. Patients with a history of prior ulcers or amputation have an increased risk of recurrence.³

Poor glycemic control. Chronic hyperglycemia contributes to vascular dysfunction, immune suppression, exacerbation of certain neuropathic symptoms, and impaired wound healing.¹

Inappropriate footwear. Ill-fitting shoes can exert excessive pressure, causing friction or shear forces, as well, particularly on high-risk areas.¹

Diabetic Neuropathic Foot Ulcer Symptoms

Diabetic neuropathic foot ulcers present with a range of clinical features, primarily determined by the extent of neuropathy, ischemia, and infection:

Painless ulceration. Due to sensory loss, patients with neuropathy often do not experience pain, leading to the above mentioned delays in recognition and treatment.¹ 

Plantar ulceration. Most ulcers occur on the metatarsal heads or heel due to repetitive trauma.¹

Callus formation. Hyperkeratosis precedes ulceration, and bleeding beneath calluses signals an impending breakdown, or the presence of an already-existing DFU underneath the callus.¹

Signs of infection. Swelling, erythema, warmth, and/or purulent discharge may indicate local or spreading infection.⁴

Etiology of Diabetic Neuropathic Foot Ulcers

The development of diabetic neuropathic foot ulcers follows a well-defined pathophysiological sequence:¹

1. Neuropathy-induced loss of sensation. LOPS results in a decreased ability or inability to perceive pain, temperature changes, and pressure.
    
2. Abnormal mechanical stress. Gait abnormalities, foot deformities, and callus formation increase plantar pressures, predisposing to ulceration.
    
3. Repetitive trauma and tissue breakdown. Minor trauma from ill-fitting shoes, walking barefoot, or pressure from calluses can lead to subdermal hemorrhage and skin breakdown.
    
4.  Infection and ischemia. A compromised immune response allows bacterial (typically polymicrobial) colonization, while PAD worsens tissue hypoxia, reducing wound healing capacity.

Treatment for Diabetic Neuropathic Foot Ulcers

Wound care and debridement.¹ Sharp debridement removes necrotic or otherwise nonviable tissue, callus, and biofilm to promote healing. To maintain a moist wound environment, use appropriate dressings, such as hydrogels or foam, to maintain optimal wound healing conditions, basing selection on individual patient findings. When suspecting infection, empiric antibiotics should cover Staphylococcus aureus and β-hemolytic Streptococcus, with tailored therapy based on wound cultures.

Offloading.¹ Total contact casting (TCC) is the the gold standard for DFU offloading techniques for plantar ulcers, redistributing pressure and minimizing shear forces.⁵ For patients unable to tolerate TCCs, alternatives include removable offloading devices and therapeutic footwear. 

Vascular intervention.^1,6 Consider endovascular procedures or bypass surgery for patients with severe PAD. Antiplatelet agents, statins, and SGLT2 inhibitors may improve vascular outcomes.

Surgical intervention. In selected cases, flexor tenotomy, Achilles tendon lengthening, or metatarsal head resection may be required.

Adjunctive therapies.^1,7 Multiple additional therapeutic options for neuropathic ulcer management may complement or assist the above interventions, such as negative pressure wound therapy (NPWT), topical oxygen therapy, or cellular and tissue-based products (CTPs), just to name a few.

Diabetic Neuropathic Foot Ulcer Prevention

Risk assessment and screening.¹ Conduct annual foot exams for patients without high-risk features, and more frequent screening (every 1–3 months) for patients with prior ulcers, PAD, or end-stage renal disease (ESRD). Assessment tools may include 10g monofilament testing, vibration perception (128 Hz tuning fork), and ankle-brachial index/toe-brachial index (ABI/TBI) measurements.

Patient education and self-care.¹ Daily foot inspections consist of checking for redness, blisters, cuts, and early signs of infection. Moisturize dry skin to prevent cracks and fissures that predispose the foot to bacterial entry. Make sure that patients dry well after bathing and do not over moisturize areas such between the toes to prevent maceration. Patients should avoid barefoot walking. Encourage protective footwear indoors and outdoors.

Therapeutic footwear.¹ Custom or customizable insoles and extra-depth diabetic shoes may reduce peak plantar pressures by 30% or more.⁸ Under Medicare, the Diabetic Therapeutic Shoe Program stipulates specifically which circumstances result in eligibility for these devices.

Integrated diabetic foot wound care.¹ Multidisciplinary teams—including podiatrists, endocrinologists, and vascular surgeons—improve ulcer healing rates and amputation prevention.

Conclusion

Diabetic neuropathic foot ulcers remain a major global and national healthcare challenge, demanding early intervention and coordinated multidisciplinary care. Prevention begins with identifying high-risk patients through routine foot screenings, patient education, and optimization of glycemic control.

Effective treatment strategies—such as sharp debridement, TCCs, infection control, and vascular intervention when indicated—are critical for wound healing and limb preservation. Adjunctive therapies, including NPWT, topical oxygen therapy, and CTPs, may enhance outcomes in select cases.

Adherence to guideline-based care, such as recommendations from the International Working Group on the Diabetic Foot and American Diabetes Association, ensures consistency with the latest clinical evidence. By combining early detection, aggressive management, and patient-centered education, healthcare teams can significantly reduce recurrence rates, infection risk, and the overall burden of diabetic neuropathic foot disease.

References 
1. Bus SA, Sacco ICN, Monteiro-Soares M, et al. Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev. 2024;40(3):e3651. doi:10.1002/dmrr.3651
2. McDermott K, Fang M, Boulton AJM, Selvin E, Hicks CW. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care. 2023;46(1):209-221. doi:10.2337/dci22-0043
3. 3. Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376(24):2367-2375.
4. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis. 2012;54(12):e132-e173.
5. International Working Group on the Diabetic Foot. IWGDF Guidelines. Available at https://iwgdfguidelines.org/guidelines-2023/ . Published 2023. Accessed March 11, 2025. 
6. Beckman JA, Schneider PA, Conte MS. Advances in revascularization for peripheral artery disease: revascularization in PAD. Circ Res. 2021;128(12):1885-1912. doi:10.1161/CIRCRESAHA.121.318261
7. Boulton AJM, Armstrong DG, Löndahl M, et al. New evidence-based therapies for complex diabetic foot wounds. Arlington (VA): American Diabetes Association; 2022 May. Available from: https://www.ncbi.nlm.nih.gov/books/NBK581559/ doi: 10.2337/db2022-02
8. Zwaferink JBJ, Custers W, Paardekooper I, Berendsen HA, Bus SA. Optimizing footwear for the diabetic foot: Data-driven custom-made footwear concepts and their effect on pressure relief to prevent diabetic foot ulceration. PLoS One. 2020;15(4):e0224010. Published 2020 Apr 23. doi:10.1371/journal.pone.0224010