Diabetic neuropathy

Last reviewed: 28 Aug 2022

Last updated: 07 Jun 2022

Hyperglycemia contributes to the pathogenesis of neuropathy in both type 1 and type 2 diabetes. Other metabolic and vascular factors, particularly hypertriglyceridemia, are important.

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

Diabetic peripheral neuropathy is the most common chronic complication of diabetes, characterized by the presence of peripheral nerve dysfunction, diagnosed after the exclusion of other causes. Pain is the outstanding complaint in most patients, but many patients are completely asymptomatic.

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

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

Definition

Diabetic neuropathy (DN) is a highly prevalent complication of diabetes (type 1 or type 2) and is characterized 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

asymptomatic
pain (peripheral)
loss of sensation (peripheral)
dysesthesia (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)

More key diagnostic factors

Other diagnostic factors

constipation (autonomic)
fecal incontinence (autonomic)
anhidrosis, heat intolerance, dry skin, or hyperhidrosis (autonomic)
hypoglycemia 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 diarrhea (autonomic)
specific mononeuropathy (peripheral)
cranial neuropathy (peripheral)
pain over lower thoracic or abdominal wall (peripheral)
thigh muscle atrophy, pain, and weakness (peripheral)

Other diagnostic factors

Risk factors

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

More risk factors

Diagnostic investigations

1st investigations to order

clinical diagnosis
fasting blood glucose
HbA1c
serum thyroid-stimulating hormone
serum vitamin B12
electrolytes, BUN, creatinine
serum lipid profile
LFTs
CBC and erythrocyte sedimentation rate
serum/urine immunoelectrophoresis
corneal confocal microscopy

More 1st investigations to order

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
heart rate variability (HRV)
gastric emptying studies
gastroduodenoscopy
barium meal
gastrointestinal manometry
hydrogen breath tests
gastric ultrasonography
gastric MRI
anorectal manometry
fecal fat
d-xylose test
urine culture
cystometry, voiding cystometrogram
postvoid urinary tract ultrasound
video-urodynamics
measurement of nocturnal penile tumescence and of penile and brachial BP
serum LH, testosterone, free testosterone, prolactin (morning tests, 8.00-9.00 a.m.)

More investigations to consider

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 epidemiologic 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 on diabetes treatment for Sanofi Aventis, Lilly, and Proctor and Gamble (P&G). RAM has reviewed an investigator-initiated grant to study long COVID from P&G. RAM is an author of references cited in this topic.

Uazman Alam, BSc, MBChB, MPHe, PhD

Senior Lecturer and Consultant Physician

University of Liverpool

Liverpool

Disclosures

UA serves on advisory boards for Eli Lilly.

Shazli Azmi, MBchB, MRCP

Consultant Physician

Diabetes and Endocrinology

Central Manchester Foundation Trust

University of Manchester

Manchester

Disclosures

SA declares that she has no competing interests.

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.

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Patient leaflets
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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

Differentials

Guidelines

Patient leaflets

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

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