Diabetic Neuropathy

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Diabetic Neuropathy

• Patrick English
• Diabetes Consultant
• Derriford Hospital

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Outline

• Size and costs of the problem
• Pathology/pathophysiology
• Risk factors
• Presentations
• Diagnosis
• Prevention and Treatment
• Algorithm/NICE

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Size and cost

• Prevalence 22.7 T1DM, 32.1 T2DM
• USA 17 of costs of treating diabetic
  complications (approx 300 per patient per year)
• UK 13 million p.a on diabetic foot
  complications
• 1900 patients with painful diabetic neuropathy in
  Derriford Catchment
• 435 requiring at least 2nd line agent for pain
• Young MJ, Boulton AJ, MacLeod AF, Williams DR,
  Sonksen PH. Diabetologia 199336(2)150-4.
• Caro, J. J., A. J. Ward, et al. (2002). Diabetes
  Care 25(3) 476-81.

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Pathology

• Axonal loss, focal demyelination regeneration
• ? conduction velocity and ? sensory thresholds

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Pathophysiology-biochemical and vascular factors
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Risk Factors

• Glycaemic control-DCCT
• ? with age 5 20-29 years, 44.2 70-79 years
• gt 50 T2DM gt60 years of age
• ? with duration of diabetes 20.8 lt 5years,
  36.8gt10 years
• ? Smoking
• ? Microalbuminuria
• ?Height
• ? Nutritional factors

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Presentations

• 3 types of neuropathy
• Progress steadily with increasing duration of
  diabetes and associated with other diabetic
  complications-common
• Acute onset with resolution over period of
  months-rare
• Pressure palsies

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Presentations

• Diffuse symmetrical sensorimotor polyneuropathy
• Predominantly sensory
• Predominantly feet
• ? pain and temperature sensation
• Parasthesiae and numbness
• Neurogenic pain/allodynia
• Neuropathic oedema
• Wasting occurs only if severe

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Diffuse symmetrical sensorimotor polyneuropathy

• Problems
• Pain and oedema
• Diabetic foot ulceration
• Present in 80 of foot ulcers
• Principle cause in 39 of ulcers
• Partly responsible in 36 of ulcers

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Autonomic Neuropathy

• Closely associated with sensorimotor neuropathy
• Signs are common if looked for (40 subjects have
  abnormal CVS tests) but symptoms are rare (lt1)
• Affects the response to hypos but not awareness
• If symptoms mortality30-50 over 10 years

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Diffuse Small Fibre Neuropathy

• T1DM
• Young, ? gt ?
• Selective damage to small nerve fibres
• Pain and temp lost but LT retained
• Symptomatic autonomic neuropathy, Charcot
  arthropathy and foot ulcers
• ? autoimmune

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Mononeuropathies

• Acute ? Secondary to ischaemia
• Pain and weakness (severe)
• Resolve over months
• Amyotrophy (Older ?gt?)
• 3rd nerve
• 6th nerve
• Truncal radiculopathies

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Diabetic Amyotrophy
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Insulin Neuritis

• Acute diffuse
• May be painful
• Follows improvement of blood glucose control
• ?steal phenomenon

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Acute diffuse painful neuropathy

• Not related to duration of diabetes or
  complications
• Association with marked weight loss
• severe burning/shooting pain, electric shocks,
  allodynia
• Resolve spontaneously, usually with weight gain,
  6-8 months. Some 2 years.
• Does not relapse
• Signs may be lacking and dissociated from symptoms

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Pressure Palsies

• ? susceptibility to pressure damage
• Limited joint mobility (soft tissue)
• Carpal tunnel
• Ulnar nerve
• Lateral popliteal nerve

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Diagnosis

• Annual review
• Enquire annually for
•          Painful neuropathy
•          Loss of sensation
•          Erectile impotence
• Note duration of DM, treatment, complications
  weight
• Ask about other manifestations of autonomic
  neuropathy if
•          Other complications are present
•          Anaesthesia is contemplated
•          Blood glucose control is erratic

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Diagnosis

• Examine
• For evidence of peripheral neuropathy annually
• LT
• OR if new symptoms
• Vibration
• LT
• ?Thermal thresholds
• ?Pain
• For postural hypotension if symptoms of autonomic
  neuropathy

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Examination-ANS

• Ewings battery
• Abnormal results common
• Valsalva-expiration for 15 secs against 40 mmHg.
  Rest 1 min then repeatx2.
• Avoid in proliferative retinopathy.
• RR max RR mingt1.21 Normal, lt1.20 abnormal.
• HR increase on standing
• RR 3015 ratio gt 1.04
• HR? at max overshoot or 15 seconds ? 15bpm
  (abnormal iflt12)

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Ewings battery

• HR variation during deep breathing (6 breaths per
  minute)
• Max-min gt 15bpm (lt10 is abnormal)
• Postural BP-2 mins after standing
• Falllt 10mmHg normal
• gt30 mmHg abnormal

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Diagnosis

• Consider differential diagnoses
• HSMN
• Ethanol
• B12/folate
• Malignancy
• Renal failure
• Drugs
• AI disease
• Cord problems
• Leprosy

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Prevention

• Control
• DCCT (1995)
• Tight control-3 neuropathy at 5 years
• Conventional-10
• UKPDS (1998)
• Tight control (HbA1c 7)-31.2 neuropathy at 15
  years
• Conventional (HbA1c 7.9)-51.7
• P0.005
• No protective effect seen for BP control

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Prevention

• Aldose reductase inhibitors
• Gamma Linoleic Acid
• Vasodilators-ACE?
• AGE inhibitors
• Antioxidants
• NGFs
• ? Smoking cessation, ? BP reduction

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Treatment-Painful neuropathy

• General Measures
• Improve glycaemic control
• Exclude or treat other contributory factors
• Alcohol excess
• Vitamin B12 deficiency/Folate
• Uraemia
• Simple analgesia-NSAID/Paracetamol
• Explanation, empathy and reassurance

Choose drugs according to dominant symptoms

• Other symptoms
• Allodynia
• Plastic film
• Leg cradle at night
• Restless legs
• Ropinirole
• Painful Cramps
• Quinine sulphate

Lancinating pain Tricyclics Anticonvulsants Dulo
xetine
Burning pain Tricyclics Anticonvulsants Duloxetin
e
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NICE CG 87 May 2009
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Treatment -ANS

• Postural hypotension
• Fludrocortisone
• NSAIDs
• Compression stockings
• Elevate the head of the bed

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Treatment -ANS

• Bladder
• Manual SP pressure
• ISC
• ? Anticholinesterase
• Cyclical antibiotics if recurrent infections
• Sweating
• ?clonidine
• Erectile dysfunction

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Treatment -ANS

• Gastroparesis
• Improve glycaemic control
• Prokinetic drugs
• Metoclopramide, domperidone, cisapride,
  erythromycin (250 mg tds)
• Octreotide?
• If severe?admit for IV fluids, IV drugs ? NG tube
  ? IV/jejunal feeding
• Diarrhoea
• Codeine/loperamide/diphenoxylate
• Clonidine or octreotide
• Treat bacterial overgrowth (oxytet/erythromycin)
  if suspected/present

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Any questions?

• www.plymouthdiabetes.org.uk