Summary
Definition
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)
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)
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
- genetic
Diagnostic tests
1st tests 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
Tests 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
- 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.)
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
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 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 references cited in this topic.
Uazman Alam, BSc, MBChB, MPHe, PhD
Reader and Consultant Physician
University of Liverpool
Liverpool
UK
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
UK
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
NY
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
MA
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
UK
Disclosures
EJ has received funding for conferences and lectures from Pfizer and Boehringer Ingelheim.
Differentials
- Uremia
- Cyanocobalamin deficiency
- Hypothyroidism
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