Diabetic neuropathy

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 22 Jun 2025

Last updated: 08 Apr 2025

Diabetic neuropathy (DN) in people with both type 1 and 2 diabetes is a complex consequence of hyperglycaemia-induced alterations in multiple biochemical pathways. Other metabolic and vascular factors, particularly hypertriglyceridaemia, are also important.

The clinical presentation comprises a broad constellation of symptoms and deficits, involving sensory, motor, and autonomic nerve fibres, and multiple organ systems.

Diabetic peripheral neuropathy is the most common chronic complication of diabetes, characterised by the presence of peripheral nerve dysfunction, diagnosed after the exclusion of other causes. Pain is the most troubling symptom for most patients, but many patients are completely asymptomatic.

Treatment has traditionally focused on control of hyperglycaemia as a means of slowing progression or delaying onset, on targeting potential pathogenic mechanisms, and on pain reduction.

Although pain is generated principally by peripheral nerve injury, there is evidence that the central nervous system may play a significant role in the disinhibition and amplification of pain. The most effective drugs in treating painful DN are centrally acting.

Definition

Diabetic neuropathy (DN) is a highly prevalent complication of diabetes (type 1 or type 2) and is characterised by the presence of symptoms and/or signs of peripheral nerve dysfunction and/or autonomic nerve dysfunction. It is diagnosed after the exclusion of other causes. Frequently, however, people with DN are asymptomatic.

History and exam

Key diagnostic factors

presence of risk factors
asymptomatic
pain (peripheral)
loss of sensation (peripheral)
dysaesthesia (peripheral)
reduced or absent ankle reflexes (peripheral)
painless injuries (peripheral)
resting tachycardia (autonomic)
impaired heart rate variability (autonomic)
urinary frequency, urgency, nocturia, incontinence, hesitancy, weak stream, or retention (autonomic)
erectile dysfunction (autonomic)
decreased sexual desire and increased pain during intercourse (autonomic)
orthostatic hypotension (autonomic)

Full details

Other diagnostic factors

constipation (autonomic)
faecal incontinence (autonomic)
anhidrosis, heat intolerance, dry skin, or hyperhidrosis (autonomic)
hypoglycaemia unawareness (autonomic)
weakness (peripheral)
history of recent falls (peripheral)
gait ataxia (peripheral)
nausea, postprandial vomiting, bloating, loss of appetite, early satiety (autonomic)
heartburn and dysphagia for solids (autonomic)
profuse and watery diarrhoea (autonomic)
specific mononeuropathy (peripheral)
cranial neuropathy (peripheral)
pain over lower thoracic or abdominal wall (peripheral)
thigh muscle atrophy, pain, and weakness (peripheral)

Full details

Risk factors

poorly controlled hyperglycaemia
prolonged duration of diabetes
older age (e.g., >70 years)
tall stature
hypertension
dyslipidaemia with elevated triglycerides
co-existence of multiple cardiovascular disease (CVD) risk factors (type 2 diabetes)
renal disease
obesity
immune dysregulation
smoking
genetic

Full details

Diagnostic investigations

1st investigations to order

clinical diagnosis
fasting blood glucose
HbA1c
serum thyroid-stimulating hormone
serum vitamin B12
renal function tests
serum lipid profile
LFTs
FBC and erythrocyte sedimentation rate
serum/urine immunoelectrophoresis

Full details

Investigations to consider

2-hour plasma glucose
nerve conduction studies (nerve conduction velocity [NCV])
electromyography (EMG)
quantitative sensory testing (QST)
skin biopsy
cardiovascular reflex testing
corneal confocal microscopy
heart rate variability (HRV)
gastric emptying studies
gastroduodenoscopy
barium meal
gastrointestinal manometry
hydrogen breath tests
gastric ultrasonography
gastric MRI
anorectal manometry
faecal fat
d-xylose test
urine culture
cystometry, voiding cystometrogram
post-void urinary tract ultrasound
video-urodynamics
Testosterone (morning)

Full details

Treatment algorithm

ONGOING

diabetic peripheral neuropathy

cranial neuropathies

limb or truncal mononeuropathies

diabetic amyotrophy

diabetic autonomic neuropathy

Contributors

Authors

Rayaz A. Malik, BSc (Hons), MSc, MBChB, FRCP, PhD

Professor of Medicine

Organizational Official for the Human Research Protection Program

Weill Cornell Medicine - Qatar

Doha

Qatar

Disclosures

RAM has been reimbursed for being on the advisory board for an epidemiological study on cardiovascular disease in type 2 diabetes and to give educational lectures on treatment of diabetes undertaken by Novo Nordisk. RAM has been reimbursed for educational lectures for Sanofi Aventis, Lilly, and Proctor and Gamble (P&G). RAM has received an investigator-initiated grant to study long COVID from P&G. RAM is an author of a number of references cited in this topic.

Uazman Alam, BSc, MBChB, MPHe, PhD

Reader and Consultant Physician

University of Liverpool

Liverpool

Disclosures

UA has received honoraria from Procter & Gamble, Viatris, Grunenthal, Eli Lilly, and Sanofi for educational meetings. UA has also received investigator-led funding from Procter & Gamble.

Shazli Azmi, MBchB, MRCP

Consultant Physician

Diabetes and Endocrinology

Central Manchester Foundation Trust

University of Manchester

Manchester

Disclosures

SA has received honoraria for educational meetings from AstraZeneca, Sanofi, Menarini, Eli Lilly, and Procter & Gamble.

Acknowledgements

Dr Rayaz Malik, Dr Uazman Alam, and Dr Shazli Azmi would like to gratefully acknowledge Dr Rodica Pop-Busui and Dr Eva Feldman, the previous contributors to this topic.

Disclosures

RPB declares that she has received speaking honoraria from Pfizer and research support from Amylin Pharmaceuticals; National Institutes of Health/National Heart, Lung, and Blood Institute; National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases; American Diabetes Association; and Juvenile Diabetes Research Foundation. RPB and EF are authors of references cited in this topic.

Peer reviewers

Zachary T. Bloomgarden, MD

Clinical Professor

Department of Medicine

Mount Sinai School of Medicine

New York

Disclosures

ZTB declares that he has no competing interests.

Rajesh K. Garg, MD

Assistant Professor of Medicine

Harvard Medical School

Division of Endocrinology

Diabetes and Hypertension

Brigham and Women's Hospital

Boston

Disclosures

RKG has received consultant fees from Aventis and Novartis, and speaker fees from Novartis.

Edward Jude, MBBS, MD, MRCP, DNB

Consultant and Honorary Senior Lecturer

Tameside General Hospital

Diabetes Centre

Ashton Under Lyne

Lancashire

Disclosures

EJ has received funding for conferences and lectures from Pfizer and Boehringer Ingelheim.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Pop-Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-54.Full text Abstract

Dyck PJ, Albers JW, Andersen H, et al; Toronto Expert Panel on Diabetic Neuropathy. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev. 2011 Oct;27(7):620-8.Full text Abstract

American Diabetes Association Professional Practice Committee. Introduction and methodology: standards of care in diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 suppl 1):S1-5.Full text Abstract

Price R, Smith D, Franklin G, et al. Oral and topical treatment of painful diabetic polyneuropathy: practice guideline update summary. Report of the AAN Guideline Subcommittee. Neurology. 2022 Jan 4;98(1):31-43.Full text Abstract

Senneville E, Albalawi Z, van Asten SA, et al. IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections. Clin Infect Dis. 2023 Oct 2:ciad527.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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Diabetic neuropathy

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

diabetic peripheral neuropathy

cranial neuropathies

limb or truncal mononeuropathies

diabetic amyotrophy

diabetic autonomic neuropathy

Contributors

Authors

Rayaz A. Malik, BSc (Hons), MSc, MBChB, FRCP, PhD

Disclosures

Uazman Alam, BSc, MBChB, MPHe, PhD

Disclosures

Shazli Azmi, MBchB, MRCP

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Zachary T. Bloomgarden, MD

Disclosures

Rajesh K. Garg, MD

Disclosures

Edward Jude, MBBS, MD, MRCP, DNB

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice