Peripheral neuropathy refers to a group of disorders involving dysfunction of the peripheral nervous system, with metabolic disease being the most common underlying cause of extremity pain. The most prevalent form, DPN, can result in complications ranging from paraesthesia to limb loss and increased mortality.¹

Its exact aetiology remains multifactorial, with proposed mechanisms including metabolic, neurovascular, and autoimmune pathways, as well as genetic, mechanical, and lifestyle factors such as alcohol use and smoking. Chronic hyperglycaemia contributes to insulin resistance, oxidative stress, inflammation, and progressive nerve damage.¹

Damage typically begins in distal sensory and autonomic fibres and progresses proximally, leading to loss of protective sensation. Management focuses on prevention, glycaemic control, lifestyle modification, patient education, foot care, and pain management.¹

Practical approaches to DPN: Screening, treatment, and ongoing patient support

With expertise in metabolic disease and endocrine disorders, Dr Coetzee unpacks practical strategies for early detection, risk stratification, and targeted management. The discussion highlights how timely screening and intervention can alter disease progression, reduce complications, and improve patient outcomes in everyday clinical practice.

Medical Academic (MA): What is the prevalence of DPN among patients with diabetes, and which early signs and symptoms should clinicians be most vigilant in identifying?

Dr Ankia Coetzee (AC): Around 50% of patients with diabetes will develop DPN during their lifetime. Importantly, this risk is modifiable with optimal glycaemic control and management of cardiometabolic factors such as dyslipidaemia and obesity. Clinicians should be alert to the classic ‘stocking-and-glove’ distribution of symptoms. Early features include:

• Positive symptoms: Burning pain, paresthesia (pins and needles), and allodynia, often worse at night
• Negative symptoms: Numbness or a ‘dead’ sensation in the feet.

Patients may not volunteer these symptoms, therefore, active enquiry (eg sleep disturbance, nocturnal discomfort) is essential.

MA: Which diabetic patients are at highest risk for developing DPN, and how does the condition typically progress if left untreated?

AC: Patients at highest risk include those with:

• Poor glycaemic control (elevated HbA1c)
• Longer disease duration (>10-years)
• Comorbidities: Hypertension, dyslipidaemia, obesity (metabolic syndrome)
• Lifestyle factors: Smoking and alcohol use.

Untreated DPN typically evolves from distal sensory loss to more proximal involvement. Loss of protective sensation predisposes to unrecognised trauma, leading to foot ulceration, infection, Charcot neuroarthropathy, and ultimately amputation.

MA: Do you routinely screen for vitamin B deficiencies in patients presenting with neuropathic symptoms, and which patients should be prioritised for testing?

AC: Screening for vitamin B deficiencies is essential, as these represent reversible causes of neuropathy that may mimic or worsen DPN. Priority groups include:

• Patients on long-term metformin (>3- to five-years)
• Elderly patients (reduced absorption)
• History of gastrointestinal surgery (eg bariatric surgery)
• Vegetarians or vegans
• Patients with rapidly progressive or disproportionate symptoms.

MA: How do you differentiate between DPN and neuropathy primarily driven by vitamin B12 deficiency in clinical practice?

AC: While overlap is common, key distinctions include:

• Vitamin B12 deficiency: Prominent proprioceptive loss (ataxia, imbalance) Reduced vibration sense Possible macrocytic anaemia.
• DNP: Predominantly small-fibre involvement early (pain, temperature) Length-dependent, metabolic pattern.

Diagnosis relies on serum B12, with adjuncts such as methylmalonic acid and homocysteine.

MA: What is the role of thiamine (vitamin B1), pyridoxine (vitamin B6), and cobalamin (vitamin B12) in the management of DPN, and is there added benefit to combination therapy?

AC: These vitamins play complementary roles in nerve health:

• Thiamine (B1): Reduces metabolic and oxidative stress (eg polyol pathway activation), benfotiamine is particularly effective
• Pyridoxine (B6): Essential for neurotransmitter synthesis and myelin maintenance
• Cobalamin (B12): Critical for myelin formation and nerve regeneration.

Combination therapy is often preferred, as these agents act synergistically — optimising the metabolic environment while supporting structural repair.

MA: At what stage of DPN would you consider initiating vitamin B supplementation, and should it be used as adjunctive therapy or only in confirmed deficiency?

AC: Vitamin B supplementation should be considered:

• At the earliest signs of neuropathy
• Proactively in high-risk groups (eg long-term metformin users)

While essential in confirmed deficiency, many clinicians use B vitamins as adjunctive therapy, recognising that subclinical deficiencies may impair nerve recovery.

MA: Given the risk of pyridoxine toxicity and variable dosing strategies, how do you balance efficacy and safety when prescribing vitamin B supplementation?

AC: Pyridoxine requires careful dosing:

• Deficiency can cause neuropathy
• Excess (typically >200mg/day) can induce sensory neuropathy

For long-term use, doses of 50–100mg daily are generally effective and safe.

MA: In patients on long-term metformin therapy, how significant is the risk of vitamin B12 deficiency, and how should this influence screening and management of neuropathy?

AC: The risk of B12 deficiency with long-term metformin use is clinically significant, affecting up to 30% of patients. Mechanistically, metformin interferes with calcium-dependent absorption of the B12–intrinsic factor complex. Other medications (eg proton-pump inhibitors) may compound this risk.

Clinical implications:

• Routine screening: Periodic (often annual) B12 testing is recommended
• Early intervention: Do not wait for anaemia — neuropathy often precedes haematological changes
• Low-normal levels matter: Even borderline levels may justify supplementation in symptomatic patients.

Conclusion

DPN is a common yet frequently under-recognised complication of diabetes, with significant implications for morbidity and quality of life. As Dr Coetzee emphasises, early identification through active symptom enquiry and risk-based screening is critical. Importantly, potentially reversible contributors such as vitamin B deficiencies — particularly in high-risk groups like long-term metformin users — should not be overlooked. A proactive, multifaceted approach that combines optimal glycaemic control with targeted nutritional support can slow progression, alleviate symptoms, and reduce the risk of devastating complications, including ulceration and amputation.

Dr Ankia Coetzee is a senior lecturer at Stellenbosch University and a specialist endocrinologist with extensive expertise in internal medicine and metabolic health. Her academic portfolio includes multiple postgraduate qualifications from Stellenbosch University, spanning Internal Medicine, Endocrinology, Diabetes and Metabolism, as well as a PhD in Endocrinology. She also holds a diploma in diabetes management from University of St Andrews.

Images: GettyImages

Reference

1. Bodman MA, Dreyer MA, Varacallo MA. Diabetic Peripheral Neuropathy. [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK442009/