Last reviewed:September 2019
Last updated:June  2019



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)

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)

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)
  • obesity
  • immune dysregulation
  • smoking

Diagnostic investigations

1st investigations to order

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

Investigations to consider

  • oral glucose tolerance test
  • 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
  • surface electrogastrography
  • 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
  • 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.)
  • sudomotor function tests
  • scintigraphic studies
  • assessment of sympathetic muscle activity
  • cardiac vagal baroreflex sensitivity testing
  • 24-hour BP profile
  • microneurography
Full details

Treatment algorithm


Professor of Medicine

Organizational Official for the Human Research Protection Program

Weill Cornell Medicine - Qatar




RAM is on speaker panels for Eli Lilly, Novo Nordisk, and Pfizer; he is on advisory boards for Novo Nordisk and Pfizer. RAM is an author of a number of references cited in this topic.

Speciality Registrar in Diabetes & Endocrinology and General Internal Medicine

University of Manchester




UA serves on advisory boards for Eli Lilly.

SpR Diabetes and Endocrinology

Diabetes and Endocrinology

University of Manchester




SA declares that she has no competing interests.

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.

Peer reviewersVIEW ALL

Clinical Professor

Department of Medicine

Mount Sinai School of Medicine

New York



ZTB declares that he has no competing interests.

Assistant Professor of Medicine

Harvard Medical School

Division of Endocrinology

Diabetes and Hypertension

Brigham and Women's Hospital




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

Consultant and Honorary Senior Lecturer

Tameside General Hospital

Diabetes Centre

Ashton Under Lyne




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

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