Diabetic neuropathy can encompass various types of neuropathies: symmetric polyneuropathy, autonomic neuropathy and other mononeuropathies and polyradiculopathies. This article will focus on diabetes-related distal symmetric polyneuropathy (DNP) in adults with diabetes. PND affects 26-50% of people with diabetes, a third of whom will have painful PND.
Symptoms develop peripherally in the feet and toes (reflecting diffuse damage to the longer sensory nerves) and may progress in the classic “gloves and stockings” distribution. PND can impair quality of life due to pain. Symptoms that affect and limit function, and the loss of protection associated with decreased sensation, can lead to foot ulceration and amputation.
PND often presents in association with microvascular complications including retinopathy and albuminuria.
The likelihood of PND and these other complications increases with the duration of diabetes. The course of PND can be changed by addressing modifiable risk factors, such as hyperglycemia, hypertension, and dyslipidemia.
Optimizing blood glucose provides the best protection against the development of PND, as it is not currently a reversible condition. PND can often progress without symptoms, or it does so with symptoms so subtle that without testing, PND goes unnoticed.
In people with PND, the risk of foot ulceration is due to a reduced ability to detect painful stimuli. The absence or reduced ability to feel an injury from chronic trauma, such as ill-fitting footwear or walking on a bony prominence, leads to hyperkeratosis, tissue destruction, and ulcerations.
When protective sensitivity is lost , burns from heaters or hot water, ingrown or thickened nails, and fungal infections can go unnoticed and cause ulceration. Once a foot ulcer develops, the future risk of new ulcers remains elevated. Peripheral arterial disease and foot deformities, such as rigid claw toes, represent the other 2 most important ulceration risk factors.
| Multimorbidity and diabetes-related peripheral neuropathy |
Most management of type 2 diabetes is done in primary care, where evidence-based treatment can improve outcomes. More than 90% of people with type 2 diabetes attending general practice in Australia live with multimorbidity.
People with type 2 diabetes and multimorbidities spend up to 80 hours per month on self-management.
Multimorbidity is also common in people with type 1 diabetes, with an even greater amount of time spent on daily self-care. People with multimorbidity may prioritize health problems based on their quality of life, for example, prioritizing analgesia for painful PND over glycemic optimization.
Consideration of patient preferences is particularly important in multimorbidity, including assessment of treatment burden and exploration of how health conditions affect patient quality of life. The Problem Areas in Diabetes scale allows for a structured approach to identifying areas of concern related to diabetes management. High levels of diabetes distress affect diabetes and blood glucose self-management, which are essential factors in preventing higher-risk foot disease.
People with multimorbidity visit general practice more frequently than those without multimorbidity. This provides opportunities to carefully evaluate PND and other microvascular alterations (including annual changes in urinary albumin/creatinine ratio and estimated glomerular filtration rate, as well as at least biennial evaluation of diabetes-related retinopathy), with the aim of development of personalized management.
While long-standing diabetes is a risk factor for neuropathy, there are other factors that can coexist and contribute to peripheral neuropathy, such as age, alcohol consumption, vitamin B12 deficiency, and thyroid disease.
| Causes of peripheral neuropathy in people with and without diabetes |
| A. Alcohol use, autoimmune conditions (e.g., rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus) |
| B. Vitamin B12/B6 deficiency |
| C. Chronic kidney disease |
| D. Drugs (e.g., metronidazole, nitrofurantoin; amiodarone; phenytoin; colchicine; chemotherapy agents: vincristine, cisplatin, and paclitaxel. |
The risk of vitamin B12 deficiency when using metformin increases to almost 20% after 5 years. The worsening of peripheral neuropathy in people with type 2 diabetes taking metformin warrants the study of vitamin B12.
| Detection of diabetes-related peripheral neuropathy |
Up to one-fifth of people with type 2 diabetes will have signs of diabetes-related distal symmetric polyneuropathy (DNP) at the time of diabetes diagnosis.
PND is a clinical diagnosis, and the extent and progression of neuropathy must be documented. As PND is often asymptomatic, guidelines recommend annual screening to find evidence of a diagnosis of PND related to type 2 diabetes. Recently, the National Diabetes Services Scheme has launched learning modules that can help assess diabetes practice. foot health.
Symptom assessment and relevant examination findings, specifically for diabetic foot, are summarized in the table below. A history of foot ulceration, inability to feel a 10-g monofilament, or absence of a pedal pulse reliably identifies future risk for foot ulceration.
| Symptoms and signs of distal symmetric polyneuropathy | |
| Symptoms | • Asymptomatic (50%) • Numbness, tingling, lack of balance (large myelinated fibers) • Pain, burning, electric shocks, shooting (small myelinated fibers) |
| Important medical history | • Previous foot ulceration • Lower extremity amputation • Peripheral arterial disease or intermittent claudication • History of chronic kidney disease • History of smoking |
| directed exam | • Inspection : hair loss, atrophy, ulcer on the toes and metatarsal heads, any pressure areas, calluses, superficial infections, fungal infections of the nails, wasting of the intrinsic muscles of the foot associated with toes in clawing, anhidrosis, skin fissures • Vascular status : palpation of foot pulses; • Pressure perception : 10 g monofilament to test sensitivity • Vibration perception : 128 Hz tuning fork on the dorsum of the big toe • Ankle and knee reflexes • Gait evaluations |
| Patient-reported outcome measure to support evaluation of diabetes-related peripheral neuropathy | • Symptom score for diabetic neuropathy |
Assessment of loss of protective sensation using a monofilament is an essential component of the physical examination. It is recommended to test in 3 places on each foot – plantar surface of the heads of the first and fifth metatarsals and the big toe – passing a 10 g monofilament until it bends.
Lack of sensitivity to monofilament at 1 or 2 sites indicates loss of protective sensitivity. Testing on sites with significant callus or active ulceration is not recommended as the results cannot be interpreted. If the monofilament test is not available, other tests such as the Ipswich touch test can be done.
It is performed by lightly touching the plantar surface of the first, third and fifth metatarsal heads and the big toe; asking the patient to close his eyes who should indicate when he feels the touch.
Bony deformities , such as prominent metatarsal heads, hallux valgus , and claw (or hammer) toes, represent areas of high pressure and potential ulceration in people with DPN. In particular, claw toes are more common due to functional loss of the intrinsic muscles of the foot due to motor neuropathy.
Calluses , which occur in response to chronic pressure on bony areas, are associated with an 11-fold increased risk of ulceration in people with PND. However, not all deformed areas will develop a callus. Therefore, a foot examination to identify foot deformity and other non-ulcerative lesions is recommended as they contribute to ulcer risk, particularly in the presence of PND.
The International Working Group on the Diabetic Foot’s Risk Stratification System is based on history and physical examination findings. According to that System, anyone at moderate to high risk requires referral to a podiatrist for people with diabetes, for any foot pathology, such as calluses, ingrown or thickened toenails, and fungal infections. Podiatry consultations are recommended to prevent foot ulcers.
Symptoms of peripheral arterial disease (eg, calf muscle pain with exertion) or signs such as absent or dull foot pulses in an adult with diabetes prompt noninvasive vascular testing.
Charcot neuroarthropathy is characterized by fracture and dislocation, which may occur in the presence of PND or other advanced neuropathies, most typically in the foot or ankle. It occurs unilaterally, with the foot hot, swollen and painless (or slightly painful). It may or may not be preceded by an injury or event, such as surgery or infection. Often, an injury is not reported, potentially due to loss of sensation.
Charcot neuroarthropathy can mimic other common conditions such as cellulitis, soft tissue injury, gout, or deep vein thrombosis. If Charcot neuroarthropathy is suspected, it is recommended to minimize weight bearing immediately and refer the diabetic patient to a High Risk Foot Service or a physician with experience in the evaluation and management of the diabetic foot. Successful treatment depends on prompt diagnosis and management with a full contact cast for several months, until cessation of inflammation and healing of the fracture (if present).
| Practical strategies to prevent foot ulcers and amputation |
For people with diabetes-related distal symmetric polyneuropathy (DNP), minor trauma related to ill-fitting shoes may precede foot ulceration.
In Australia, international guidelines have been adapted to the local context, prioritizing recommendations based on evidence and education.
For people with PND, the first step is education of the diabetes patient and their family members to help them understand that foot sensitivity is reduced. A foot action plan should be developed that includes structured foot care education and shoe inspection.
Initial discussion in general practice (while awaiting podiatry review) for moderate and high risk people may include advice on safe footwear, avoidance of thermal injuries and learning to check their feet to prevent complications.
Essential discussion includes the importance of foot protection. People with diabetes should not walk barefoot or in socks, both indoors and outdoors, and should trim their toenails in a straight line. If increased activity load on the feet is noted, people with diabetes should be encouraged to wear appropriate footwear and increase self-monitoring for any signs of injury.
All people with diabetes and loss of protective sensation or peripheral arterial disease should have their feet daily inspected, carefully drying the interdigital folds, and applying topical emollients to prevent skin dryness. People with PND and their families should understand that foot problems can occur without pain and that they should seek treatment quickly for any foot problems that arise.
| Risk Stratification System of the International Working Group on the Diabetic Foot (IWGDF) | |||
| WGDF Category | Ulcer risk | Risk factor’s | Reassessment and referral |
| 0 | Very low | No loss of protective sensation or peripheral arterial disease | Annual evaluation |
| 1 | Low | Loss of protective sensation or peripheral arterial disease | Reevaluation every 6 to 12 months |
| 2 | Moderate | Loss of protective sensation and peripheral arterial disease o Loss of protective sensation and foot deformity o Peripheral arterial disease and foot deformity | Reevaluation every 3 to 6 months Referral to Podiatry Within 6 to 8 weeks |
| 3 | High | Loss of protective sensation or deformity of the foot and one of: • history of a foot ulcer • lower limb amputation • end-stage renal disease | |
| Conclusions |
All adults with diabetes require annual evaluation for protective sensation loss. Loss of protective sensation in a person with diabetes indicates a foot at risk.
General practitioners can reduce the development of diabetes-related foot ulcers through increased foot monitoring, foot self-care education and appropriate footwear, and timely referral to podiatry for non-ulcer foot problems.
