Management of type 2 diabetes: A handbook for general practice

Microvascular complications: Diabetes-related neuropathy

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Last revised: 17 Sep 2020

Grade: B

All patients should be screened for diabetic peripheral neuropathy, starting at diagnosis of type 2 diabetes and at least annually thereafter

Grade: A, level 1

Screening for peripheral neuropathy should be conducted by assessing loss of sensitivity to the 10 g monofilament, or loss of sensitivity to vibration at the dorsum of the great toe
The following agents may be used alone or in combination to relieve painful peripheral neuropathy:
  • anticonvulsants
    • pregabalin (Grade A, level 1)
    • gabapentin (Grade B, level 2)
    • valproate (Grade B, level 2)
  • antidepressants (Grade B, level 2)
    • amitriptyline
    • duloxetine
    • venlafaxine
  • topical nitrate spray (Grade B, level 2)
  • opioid analgesics (Grade B, level 2)

Grade: B, level 2

People with type 2 diabetes should be treated with intensified glycaemic control to prevent the onset and progression of neuropathy 
These recommendations are drawn from the most recent recommendations from organisations including the National Health and Medical Research Council (NHMRC), the Scottish Intercollegiate Guidelines Network (SIGN), Diabetes Canada, the American Diabetes Association (ADA) and other relevant sources. Refer to ‘Explanation and source of recommendations’ for explanations of the levels and grades of evidence.

Diabetic neuropathies increase with age, duration of diabetes and level of control of diabetes. They are heterogeneous, with diverse clinical manifestations, and may be focal or diffuse.

Symptoms include pain and paraesthesia, and if the autonomic nervous system is involved, gastrointestinal, bladder and sexual problems may arise. These increase the patient’s burden of self-care and overall management. Foot ulceration and amputation are important and costly sequelae of diabetic neuropathy2 (refer to the section ‘Microvascular complications: Foot care’). 

Peripheral neuropathy

Manifestations of diabetes-related peripheral neuropathy include:

  • polyneuropathy – diffuse and symmetrical neuropathy (most common)
  • mononeuropathy
  • polyradiculoneuropathy
  • thoracic radiculopathy
  • cranial neuropathy.

Autonomic neuropathy

Autonomic neuropathy may result in:

  • orthostatic hypotension with >20 mmHg drop
  • impaired and unpredictable gastric emptying (gastroparesis), which can cause a person’s blood glucose levels to be erratic and difficult to control. Pro-kinetic agents such as metoclopramide, domperidone or erythromycin may improve symptoms
  • diarrhoea, chronic constipation, reduced anal sphincter control
  • delayed/incomplete bladder emptying, urinary incontinence
  • erectile dysfunction and retrograde ejaculation in males
  • reduced vaginal lubrication with arousal in women
  • loss of cardiac pain, ‘silent’ ischaemia or myocardial infarction
  • sudden, unexpected cardiorespiratory arrest, especially under anaesthetic or treatment with respiratory-depressant medications
  • difficulty recognising hypoglycaemia (hypoglycaemic unawareness)
  • unexplained ankle oedema.

Before any treatment is instigated, exclusion of non-diabetic causes of neuropathy is suggested. This includes assessment for vitamin B12 deficiency, hypothyroidism and renal disease, and a review of neurotoxic drugs, including excessive alcohol consumption.

The clinical focus is on prevention via optimising glycaemic management and early recognition, facilitated by good history and routine sensory testing.


People with type 2 diabetes should be checked for diabetic peripheral neuropathy at diagnosis, and at least annually thereafter.1

Tests to assess for diabetic peripheral neuropathy are shown in Box 1. Combinations of more than one test have >87% sensitivity in detecting diabetic peripheral neuropathy. Loss of 10 g monofilament perception and reduced vibration perception predict foot ulcers.3

Several neuropathy scoring systems (diabetic neuropathy symptom score, neuropathy impairment score and Michigan neuropathy screening instrument) may be used with examination to confirm diagnosis and assess severity.4–6

Motor neuropathy sometimes occurs, with muscle wasting, weakness and abnormalities of gait. This can contribute to foot problems by altering the biomechanics of the ankle and foot.

Cardiovascular autonomic neuropathy should be suspected with resting tachycardia (>100 beats per minute) or orthostatic reduction in blood pressure (a fall in systolic blood pressure >20 mmHg on standing without an appropriate heart rate response). This applies to patients not currently on antihypertensive agents that may cause variations in blood pressure responsiveness, such as β-blockers. It is associated with increased cardiac event rates.

Box 1. Tests to assess for peripheral neuropathy3

  • Small fibre:
    • pinprick sensation
  • Large fibre:
    • vibration perception (using a 128 Hz tuning fork)
    • 10 g monofilament pressure sensation at the distal plantar aspect of both great toes and metatarsal joints
    • assessment of ankle reflexes
    • loss of protective sensation (10 g monofilament)


Management of diabetes-related neuropathy mainly involves professional assessment and foot care to prevent diabetes-associated foot disease. The appearance of peripheral neuropathy should prompt review of glycaemic control and consideration of intensified management to prevent progression.2

The pain of peripheral neuropathy can be difficult to manage, although there is evidence that several agents can improve symptom control and quality of life.

  • Tricyclic medications could be considered as a first-line treatment.
  • Gabapentin provides pain relief of a high level in approximately one-third of people who take this medication for ‘painful neuropathic pain’.7
  • Pregabalin at daily oral doses of 300–600 mg provides high levels of benefit for some patients experiencing neuropathic pain, including painful diabetic neuropathy.8

For information about the Foot Forward program to prevent amputation, contact Diabetes Australia.

  1. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2019;42:S1–S194.
  2. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2018;42:S1–S325.
  3. Pop-Busui R, Boulton A, Feldman E, et al. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care 2017;40(1):136–54.
  4. Yang Z, Chen R, Zhang Y, et al. Scoring systems to screen for diabetic peripheral neuropathy (Protocol). Cochrane Database Syst Rev 2014;3:CD010974.
  5. Xiong Q, Lu B, Ye H, Wu X, Zhang T, Li Y. The diagnostic value of Neuropathy Symptom and Change Score, Neuropathy Impairment Score and Michigan Neuropathy Screening Instrument for diabetic peripheral neuropathy. Eur Neurol 2015;74(5–6):323–27.
  6. Meijer JW, Smit AJ, Sonderen EV, Groothoff JW, Eisma WH, Links TP. Symptom scoring systems to diagnose distal polyneuropathy in diabetes: The Diabetic Neuropathy Symptom score. Diabet Med 2002;19(11):962–65.
  7. Moore RA, Wiffen PJ, Derry S, et al. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011;16(3):CD007938.
  8. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009;8(3):CD007076.
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