Diabetic peripheral neuropathy (DPN) Updated 2026

Evidence-based clinical review built on the ADA Standards of Care 2025, IWGDF 2023 and AAN 2022 Practice Guideline recommendations together with recent meta-analyses: screening, foot risk stratification, multimodal exercise and prevention of complications.

Definition, epidemiology and risk factors

The diabetic peripheral neuropathy (DPN), or more precisely diabetic distal sensorimotor polyneuropathy (DSPN), covers a set of lesions of the peripheral nervous system linked to diabetes mellitus. It is the most common chronic complication of diabetes and affects up to 50% of patients with diabetes during their lifetime¹. A 2023 systematic review of 19 Pakistani studies (n = 8,487) found a pooled prevalence of 43.2%², illustrating the geographical variability tied to diagnostic criteria. Among older people without diabetes, 25 to 32% have a peripheral neuropathy³, underlining that ageing is a risk factor in its own right.

The non-modifiable risk factors are the duration of diabetes, age and genetic predisposition. The main modifiable factors are:

• The glycaemic control measured by HbA1c: a linear relationship holds between a raised HbA1c and the incidence of DPN (DCCT/EDIC for type 1, ACCORD for type 2)⁶.
• The high blood pressure, the dyslipidaemia (raised triglycerides in particular: Pop-Busui 2024 Neurology⁷), the obesity and the metabolic syndrome.
• The smoking and the excessive alcohol consumption.

It is essential to remember that a neuropathy can be detected as early as the prediabetes stage⁴, which justifies early screening and targeting of cardiometabolic risk factors well before diabetes is formally diagnosed. Also worth noting are the non-diabetic causes of neuropathy that must be ruled out systematically: B12 deficiency (often worsened by long-term metformin), hypothyroidism, alcohol consumption, chemotherapy, inflammatory neuropathies (CIDP) and paraneoplastic causes⁸.

Pathophysiology and natural history

The pathophysiology of DPN is multifactorial, but chronic hyperglycaemia is its main driver⁹. Excess intracellular glucose activates several damaging metabolic pathways that injure the neurons, the Schwann cells and the nourishing microvessels (vasa nervorum) :

• Polyol pathway : conversion of glucose into sorbitol by aldose reductase, osmotic accumulation, depletion of myo-inositol and NADPH.
• Advanced glycation end-products (AGEs) : non-enzymatic binding of glucose to proteins, structural damage and activation of RAGE receptors (chronic inflammation).
• Oxidative stress : overproduction of reactive oxygen species (ROS) that overwhelm antioxidant defences and cause mitochondrial dysfunction.
• PKC activation and vascular disturbance (nerve ischaemia).

The natural history follows a "dying-back" retrograde axonopathy⁹: the longest axons are hit first, which explains the typical distal, symmetrical "stocking" distribution pattern. Progression runs from the feet to the legs and then, later, from the fingers to the hands ("stocking and glove").

This two-phase course carries major clinical weight: a patient can move from a painful symptomatic phase to a pain-free one (the "burning feet" that go quiet), falsely reassuring but in fact more dangerous, because it heralds the loss of protective sensation and exposure to injuries that go unnoticed. The 5-year mortality after a diabetic foot ulcer reaches 30.5%, and 56.6% after major amputation¹⁰: figures comparable to several cancers (breast 9%, lung 80%, all cancers pooled 31%).

History: characterising symptoms and risk factors

The history is the first step in diagnosing DPN, and often the most productive one. It must explore several dimensions systematically¹.

Characterising the symptoms: ask for a precise description of the sensations, distinguishing two categories:

• The positive symptoms (small fibre involvement, which comes earlier): burning, tingling, pins and needles, electric shocks, allodynia (pain from a normally non-painful stimulus), often worse at night².
• The negative symptoms (large fibre involvement, which comes later): numbness, "cotton wool" sensations or a feeling of walking on cotton wool, unsteadiness when walking, distal muscle weakness, unexplained falls³.

Distribution and timing: typical DPN presents with a distal, symmetrical, ascending "stocking" distribution. The first symptoms affect the toes then climb upwards; at a more advanced stage the hands are involved ("stocking and glove"). Any atypical presentation (asymmetrical, predominantly motor, rapid progression over a few weeks, proximal involvement) must raise the suspicion of another cause⁴.

Risk factors and history: always establish the following:

• Duration of diabetes, recent HbA1c, type of antidiabetic treatment.
• Cardiometabolic comorbidities: hypertension, dyslipidaemia, obesity.
• Alcohol intake, smoking, occupation (toxic exposure).
• Past history: chemotherapy, bariatric surgery (B12 deficiency), kidney disease (uraemia), thyroid disorders, autoimmune disease.
• Foot history: ulcers, amputations, usual footwear.

Clinical examination: monofilament, tuning fork and differential diagnosis

In a patient with diabetes and typical symptoms, DPN can be diagnosed clinically without resorting to electromyography (EMG), in line with the ADA Standards of Care 2025⁵. The minimum recommended examination comprises:

The ADA recommends annual screening of every patient with type 2 diabetes from diagnosis onwards, and 5 years after diagnosis for type 1 diabetes⁵. Loss of protective sensation detected with the monofilament is a major risk factor for ulceration and must trigger intensified preventive measures.

Mandatory differential diagnosis: before concluding that this is DPN, rule out:

• Vitamin B12 deficiency (very common with long-term metformin: measuring the level is essential)⁸.
• Hypothyroidism (TSH).
• Alcoholic neuropathy (targeted questioning, GGT, MCV).
• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): suspect it if the presentation is asymmetrical or motor, if progression runs beyond 8 weeks, or if there is a proximal deficit.
• Toxic neuropathies : chemotherapy (oxaliplatin, vincristine, taxanes), antiretrovirals.
• Autoimmune diseases : Sjögren, lupus, sarcoidosis, vasculitis.
• Paraneoplastic causes : if there is unexplained weight loss or an inflammatory syndrome.
• Chronic kidney failure with uraemia.

A minimum laboratory work-up in the presence of a polyneuropathy comprises: full blood count, electrolytes, creatinine, blood glucose and HbA1c, TSH, B12, plasma protein electrophoresis⁵.

Classification: Toronto, NDS and IWGDF

The Toronto classification (Tesfaye et al. 2010)⁹ stages DPN in four categories: possible, probable, confirmed, subclinical. This stratification has prognostic and therapeutic value:

• Possible DPN : symptoms OR clinical signs.
• Probable DPN : symptoms AND clinical signs (2 or more).
• Confirmed DPN : signs + electrophysiological abnormality.
• Subclinical DPN : abnormal nerve conduction with no sign or symptom.

The Neuropathy Disability Score (NDS) is a clinical score combining vibration, pain, temperature and ankle reflexes (0-10) that predicts ulcer risk⁵. But for physiotherapy practice in France, it is the IWGDF foot risk stratification system that structures management best: that is the subject of the next chapter.

IWGDF 2023 stratification: a major clinical tool

The International Working Group on the Diabetic Foot (IWGDF) has published the international reference recommendations for the prevention and management of the diabetic foot since 1999. The IWGDF 2023update¹ (published in 2024 in Diabetes/Metabolism Research and Reviews) introduces a foot risk stratification in four categories that guides how often patients are reviewed and how intensive preventive measures should be.

This classification has two major clinical uses:

1. Adapting the follow-up interval for physiotherapy and podiatry to the real level of risk: avoiding over-medicalisation of risk 0 and concentrating resources on risk 2-3.
2. Justifying therapeutic footwear and insoles: essential from IWGDF 2 onwards, they can cut plantar pressures by 30% or more³ and prevent ulcer recurrence⁴.

The daily foot self-inspection is non-negotiable from IWGDF 1 onwards and must be taught systematically, with a mirror for the sole of the foot when mobility is reduced. The cumulative evidence for structured therapeutic education shows a reduction of about 50% in ulcer risk⁵ (RR 0.54; 95% CI 0.29-1.00).

The Charcot foot: an emergency that is often missed

The Charcot neuroarthropathy is a potentially devastating complication of DPN, marked by progressive destruction of the bones, joints and soft tissues of the foot. Its prevalence in people with diabetes is estimated at between 0.1% and 13%, rising to 29-35% when severe neuropathy is present⁶. The acute form is an emergency: missing it leads to irreversible joint destruction and exposes the patient to amputation.

Typical clinical presentation of acute Charcot :

• The hot foot (temperature difference > 2 °C compared with the other foot, easy to measure with an infrared thermometer).
• The red and swollen foot.
• Pain is moderate or absent and strikingly out of proportion to the inflammatory signs, which is the major diagnostic trap.
• A history of minor trauma (sometimes) or often no trigger at all.
• Diabetes usually poorly controlled, neuropathy established.

The differential diagnosis includes: cellulitis or erysipelas (more marked pain, inflammatory syndrome, raised white cell count), deep vein thrombosis, osteomyelitis, gout. Further imaging (MRI first choice, technetium bone scan if MRI is contraindicated) confirms the diagnosis and defines its extent⁷.

Initial physiotherapy management of acute Charcot :

• Total offloading is imperative using a total contact cast (TCC) or a removable CROW boot, for 3 to 6 months on average (until the temperature difference has normalised)⁷.
• Regular monitoring of temperature, of oedema and of inflammatory markers.
• After the acute phase: progressive rehabilitation of weight-bearing, adaptation of footwear (custom therapeutic shoes if there are deformities), compensatory proprioceptive work.
• Long-term monitoring: risk of contralateral recurrence is high (up to 30% at 5 years)⁸.

Hierarchy of recommended interventions

The management of DPN rests on a clear hierarchy validated by the international guidelines (ADA 2025, AAN 2022, IWGDF 2023)¹⁻³. The aim is not only to relieve pain but also to slow the progression and to prevent the devastating complications (ulcers, amputations, Charcot).

1. Optimal glycaemic control: the DCCT/EDIC (type 1) and ACCORD/VADT (type 2) trials showed that improving glycaemic control reduces the incidence of DPN and slows its progression⁴. It is the only intervention whose effect on the progression of the nerve disease is clearly established. Every patient with DPN must have regular diabetology review with optimisation of HbA1c targets.

2. Annual foot assessment and education: in line with the ADA Standards 2025¹, every person with diabetes must have an annual foot assessment (monofilament, tuning fork, pulse palpation, search for deformities). Structured therapeutic education (daily inspection, choice of shoes, skin hygiene, warning signs) reduces the risk of ulceration by about 50%⁵.

Multimodal exercise: the therapeutic mainstay

Physical exercise is now a first-line intervention validated by recent meta-analyses⁶,⁷. The meta-analysis by Streckmann et al. (2022, Sports Medicine)⁶ confirms a moderate to large effect on:

• The neuropathic pain (significant reduction on the NRS and BPI scales).
• The static and dynamic balance: a reduction in the risk of falling.
• The walking speed and endurance.
• The nerve function (improved nerve conduction, and even intra-epidermal fibre density in some patients).

Current consensus favours a multimodal approach combining 4 components:

Safety of exercise when DPN is present: contrary to an old belief, exercise is not contraindicated when DPN is present, including when protective sensation has been lost. The safety principles are:

• Foot inspection before and after every session.
• Suitable footwear (sports shoes, seamless socks).
• Skin moisturising to prevent cracks.
• Prefer low-impact activities (swimming, stationary bike, cross-trainer) when IWGDF ≥ 2 or deformities are present.
• Avoid running on uneven ground when LOPS is marked.
• Initial supervision by a physiotherapist to confirm safety and progress gradually.

Adjuncts, pharmacotherapy and psychological factors

Pharmacotherapy for neuropathic pain: the official recommendation of the American Academy of Neurology (AAN 2022 Practice Guideline Update, Price et al.)² brings together the best available data:

The AAN explicitly recommends not prescribing opioids as first-line treatment for diabetic neuropathic pain, because of the limited long-term benefit and the risks of misuse and dependence². Prescribing remains a medical responsibility, but the physiotherapist must know the principles in order to fit in with the treatment and work with the patient's GP.

Adjunctive physical modalities: several modalities are used in clinical practice, but their level of evidence varies:

• TENS : the Gibson 2019 Cochrane meta-analysis⁸ concludes that the evidence is of low quality for chronic neuropathic pain. It can be a short-term adjunct, without replacing active approaches.
• Photobiomodulation (low-level laser) : heterogeneous results, low to moderate level of evidence; no strong recommendation.
• Manual therapy / neural mobilisation : limited evidence, isolated trials; clinical use justified only when there are associated mobility restrictions.
• Focal or platform mechanical vibration : promising preliminary trials, but low quality of evidence.

The psychological dimension: chronic pain, fear of falling and loss of function are associated with high levels of anxiety, depression and catastrophising⁹. These factors amplify the perception of pain and undermine adherence to foot care, creating a vicious circle. Systematic screening (HADS, PHQ-9) and referral for Cognitive behavioural therapy (CBT) or a mindfulness-based approach are indicated in patients with a marked psychological component¹⁰.

Making the patient an active partner through self-management

Patient empowerment is a central pillar for preventing the worsening of DPN and the dreaded diabetic foot ulcer. Moving from passive care to active self-management rests on structured therapeutic education programmes that have proved effective not only in improving knowledge but also in reducing the incidence of ulcers and amputations¹.

The four pillars of self-management :

• Tight glycaemic control: the most effective measure for slowing the progression of DPN. It means regular HbA1c monitoring and close collaboration with the diabetologist².
• Daily foot inspection: the most effective preventive act. Look for redness, blisters, cuts and skin changes. Use a mirror if mobility does not allow the sole to be seen. Teaching this practice reduces the risk of ulceration by about 50%¹.
• Suitable footwear: essential from IWGDF 2 onwards. Custom therapeutic shoes and personalised orthoses can cut peak plantar pressures by 30% or more³. Teach the basic rules: check inside the shoe before putting it on, seamless socks in natural fibres, never walk barefoot.
• Moisturising and skin care: apply a moisturising cream daily (avoiding the spaces between the toes to limit maceration). This preserves skin elasticity and barrier function⁴.

The effectiveness of these programmes depends on how far they are personalised (health literacy, socio-cultural context, cognitive capacity) and on how far they are repeatedly reinforced over time. One-off education is not enough: a sustained approach with regular reminders is needed⁵.

Safe return to sport and activity

Physical activity is a major therapeutic intervention for patients with DPN. Beyond glycaemic control, it has direct effects on nerve function, balance and quality of life⁶,⁷. The return must, however, be gradual, supervised and tailored to avoid iatrogenic injury, particularly in patients who have lost protective sensation.

Four steps to a safe return :

1. A full preliminary assessment: quantify the sensory loss (monofilament), assess muscle strength, joint stability, static and dynamic balance (Berg Balance Scale, Timed Up & Go, Tinetti). Stratify the foot risk (IWGDF). Examine the feet (callus, deformities, previous ulcers).
2. A multimodal programme: combine aerobic + strengthening + balance + flexibility (see chapter 3). Favour low-impact activities when IWGDF ≥ 2 (swimming, stationary bike, cross-trainer, Tai Chi, adapted yoga). Mao 2023 SR/MA⁷ confirms that Tai Chi improves postural control.
3. Gradual, monitored progression: the principle of progressive overload, increasing duration or intensity in steps of no more than 10% per week. Watch for pain or skin lesions. Inspect the feet before and after every session.
4. A focus on balance and fall prevention: patients with DPN have roughly a threefold higher risk of falling (Hicks 2023⁸). Specific exercises on unstable surfaces (under supervision), Tai Chi and adapted yoga have proved effective⁷.

Activities to favour vs to avoid :

Critique and controversies

Although education and exercise command consensus, several challenges remain. The first is long-term adherence : many studies show a significant fall in adherence to self-care behaviour after a few months⁹. The move from supervised education to independent self-management remains the weak link. Reinforcement strategies (telephone reminders, apps, telemedicine) are promising but their scientific validity is uneven.

The second concerns the "optimal dose" of exercise. The multimodal recommendations command consensus, but the ideal frequency, intensity and duration are still debated. More intensive programmes (HIIT) have shown marked metabolic benefits, but they raise the risk of injury in an at-risk population; the benefit-risk balance must be reassessed for each individual⁶.

Finally, the emergence of wearable technologies and health apps (pressure sensors, connected insoles, home infrared thermometers) opens promising prospects for remote monitoring and the early detection of incipient Charcot, but the risk is of creating a digital divide that excludes the less tech-savvy patients, who are often the most at risk⁵.

A "classic" case: DPN with a plantar ulcer

A representative case is reported by Waghe and Athawale (2024) in Cureus¹: a man aged 62 years, with diabetes for 25 years, presents with pain and blisters on the right foot that progressed to an ulcer once they burst. Examination finds reduced joint range and muscle strength in the affected foot, on a background of distal sensory neuropathy.

Multimodal management :

• Targeted strengthening exercises for the foot and ankle.
• Infrared radiation therapy (adjunct).
• Sensory integration to stimulate the altered perception.
• Therapeutic foot-care education (inspection, footwear, hygiene).

Outcomes measured on the NRS (Numeric Pain Rating Scale), the WHO-QOL and the DFSQ-UMA (Diabetic Foot Self-Care Questionnaire) showed substantial improvement by the end of the programme¹. This case illustrates the value of a multimodal approach combining exercise, physical modalities and education.

Complex case: Charcot neuroarthropathy with equinovarus deformity

The case of Chitlange, Padmawar and Phansopkar (2023) in Cureus² illustrates the management of a patient aged 38 years with a Charcot foot and equinovarus deformity following earlier fractures and K-wire stabilisation. Rehabilitation comprised:

• Initial phase: mandatory total offloading (TCC) to stabilise the inflammatory process.
• Recovery phase: progressive rehabilitation of weight-bearing, joint work at the ankle and hindfoot, tailored muscle strengthening.
• Adaptation of therapeutic footwear and of orthoses to prevent ulcers over the new bony deformities.
• Intensive proprioceptive work to compensate for the new shape of the foot.

This case brings out three major lessons: (1) the total offloading is non-negotiable in the acute phase; (2) post-acute rehabilitation must be very gradual; (3) secondary prevention (footwear, orthoses) is essential, because the Charcot foot carries a high risk of ulcers and of contralateral recurrence.

Hierarchy of evidence and the limits of case studies

Case studies are valuable for illustrating an approach, flagging rare presentations or prompting reflection. But their level of evidence is the lowest (n=1, level 5 of the Oxford CEBM hierarchy; very low quality according to GRADE). They can never demonstrate efficacy.

Critique and controversy

Case studies must be read critically. Their main limitation is their low level of evidence (n=1): no generalisation is possible. Positive results may be due to the placebo effect, to the natural course of the disease, or to features specific to the patient (motivation, comorbidities, family support).

There is a major publication bias at work: cases reporting spectacular therapeutic successes or atypical presentations are far more likely to be published than those describing failures or unremarkable courses. This can create a falsely optimistic picture of how effective some interventions are.

Finally, the fabrication bias also exists: the "grey" literature and some journals with limited peer review publish fictitious case studies or extrapolated data. Always check the source (PMID, DOI, PMC) before citing a case as a clinical example.

Red flags, yellow flags and referral

One of the physiotherapist's most important skills is to recognise the limits of their scope of practice and to identify the situations that call for further expertise. Effective triage is a guarantee of safety and efficiency.

Red flags specific to DPN: beyond the general framework of spinal red flags (Finucane 2020 IFOMPT)¹, several signs specific to DPN must trigger prompt medical referral:

Yellow flags: a concept introduced by Nicholas 2011², yellow flags are the psychosocial factors that predict pain and disability becoming chronic. In the patient with DPN they include:

• Mistaken beliefs about pain ("pain means tissue damage that is getting worse").
• Catastrophising and fear of movement (kinesiophobia).
• Activity avoidance behaviour.
• Anxiety and depressive symptoms.
• Social isolation, poor support.
• Work-related litigation or a compensation claim.

The presence of yellow flags justifies working with a health psychologist or a chronic pain specialist. A cognitive behavioural (CBT) or mindfulness-based approach can significantly improve quality of life and adherence to care³.

Structured interprofessional collaboration: the complexity of the diabetic foot demands a team:

• Diabetologist or GP : optimisation of glycaemic control, drug prescribing, follow-up.
• Podiatrist : regular foot care, insoles, footwear advice.
• Therapeutic education nurse : structured therapeutic patient education (ETP) programmes.
• Dietitian : nutritional balance, weight loss if obesity is present.
• Psychologist : yellow flags, CBT, chronic pain management.
• Vascular surgeon : revascularisation if PAD is severe.
• Orthopaedic or maxillofacial surgeon : deformities, debridement, amputations.

PROMs, COS and barriers to EBP

Measuring outcomes with validated PROMs: systematic use of Patient-Reported Outcome Measures (PROMs) has become a standard in evidence-based practice⁴. For DPN, the validated tools include:

PROMs have a threefold purpose: (1) to quantify progress over time; (2) to set concrete goals aiming at the "minimal clinically important difference" (MCID); (3) to support shared decision-making with the patient⁴. Their implementation, however, runs up against a lack of time and training.

Core Outcome Sets (COS): to standardise measurement internationally, the scientific community is promoting the adoption of consensus tool sets for each condition. This makes studies more comparable and allows more data to be pooled for future meta-analyses⁵.

Barriers to EBP and strategies for overcoming them: the systematic review by Scurlock-Evans et al. (2014)⁶ identifies three main barriers perceived by physiotherapists:

1. Lack of time : productivity pressure, administrative constraints.
2. Lack of skills : difficulty searching, appraising and interpreting the literature.
3. Lack of organisational support : a culture unfavourable to continuing education, limited access to databases.

Concrete strategies to counter them:

• Time : build PROM collection into digital tools (tablets, apps), and run "journal clubs" with protected time.
• Skills : continuing education (critical appraisal, statistics), use of pre-appraised resources (PEDro, Cochrane, guidelines).
• Support : organisational leadership that favours EBP, funding for training, EBP mentor roles within teams⁶.

Critique and controversy: beyond the guidelines

Applying guidelines blindly raises fundamental questions. The first trap is the "data graveyard" : collecting PROMs becomes an end in itself, with the results never used to adapt treatment or to discuss matters with the patient⁷. Without a clinical feedback loop, measurement loses its meaning.

The second is the tension between standardisation and personalisation. Guidelines are based on the homogeneous populations of clinical trials, whereas the clinician faces patients with multiple comorbidities, unique psychosocial contexts and varied preferences. The art of physiotherapy lies in the ability to navigate between scientific rigour and the flexibility that the humanity of care demands ("treat the person, not just the diagnosis")⁸.

Finally, the fear of missing serious pathology can lead to "flag inflation" and over-referral, cancelling out the efficiency gains of the physiotherapist as first contact¹. The balance between caution and confidence in clinical reasoning remains a constant challenge, one that only experience and continuing education can resolve.