Diabetic
Neuropathy
Patrick English
Diabetes Consultant
Derriford Hospital
www.plymouthdiabetes.org.uk/
Outline
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Size and costs of the problem
Pathology/pathophysiology
Risk factors
Presentations
Diagnosis
Prevention and Treatment
Algorithm/NICE
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Size and cost
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1.
2.
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
1993;36(2):150-4.
Caro, J. J., A. J. Ward, et al. (2002). Diabetes Care 25(3): 476-81.
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Pathology
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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
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Glycaemic control-DCCT
 with age: 5% 20-29 years, 44.2% 7079 years
> 50% T2DM >60 years of age
 with duration of diabetes: 20.8% <
5years, 36.8%>10 years
 Smoking
 Microalbuminuria
Height
? Nutritional factors
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Presentations
3 types of neuropathy:
1.
Progress steadily with increasing
duration of diabetes and
associated with other diabetic
complications-common
2.
Acute onset with resolution over
period of months-rare
3.
Pressure palsies
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Presentations
Diffuse symmetrical
sensorimotor polyneuropathy
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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
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Closely associated with
sensorimotor neuropathy
Signs are common if looked for
(40% subjects have abnormal CVS
tests) but symptoms are rare (<1%)
Affects the response to hypos but
not awareness
If symptoms: mortality=30-50% over
10 years
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www.plymouthdiabetes.org.uk/
Diffuse Small Fibre Neuropathy
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T1DM
Young, ♀ > ♂
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 ♂>♀)
 3rd nerve
 6th nerve
 Truncal radiculopathies
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Diabetic Amyotrophy
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Insulin Neuritis
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Acute & diffuse
May be painful
Follows improvement of blood
glucose control
?steal phenomenon
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Acute diffuse painful
neuropathy
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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
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 susceptibility to pressure
damage
Limited joint mobility (soft
tissue)
Carpal tunnel
Ulnar nerve
Lateral popliteal nerve
Diagnosis
Annual review
 Enquire annually for:
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Painful neuropathy
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Loss of sensation
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Erectile impotence
 Note duration of DM, treatment,
complications & weight
 Ask about other manifestations of
autonomic neuropathy if:
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Other complications are present
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Anaesthesia is contemplated
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Blood glucose control is erratic
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Diagnosis
Examine:
 For evidence of peripheral
neuropathy annually
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LT
OR if new symptoms
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Vibration
LT
?Thermal thresholds
?Pain
For postural hypotension if
symptoms of autonomic neuropathy
Examination-ANS
Ewing’s battery
Abnormal results common
 Valsalva-expiration for 15 secs against 40
mmHg. Rest 1 min then repeatx2.
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Avoid in proliferative retinopathy.
RR max : RR min>1.21 =Normal, <1.20 =
abnormal.
HR increase on standing
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RR 30:15 ratio > 1.04
HR at max overshoot or 15 seconds  15bpm
(abnormal if<12)
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Ewing’s battery
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HR variation during deep breathing
(6 breaths per minute)
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Max-min > 15bpm (<10 is
abnormal)
Postural BP-2 mins after standing
Fall< 10mmHg normal
 >30 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)
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Tight control-3% neuropathy at 5 years
Conventional-10%
UKPDS (1998)
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Tight control (HbA1c 7%)-31.2%
neuropathy at 15 years
Conventional (HbA1c 7.9%)-51.7%
P=0.005
No protective effect seen for BP control
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Prevention
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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
Burning pain
Tricyclics
Anticonvulsants
Duloxetine
Lancinating
pain
Tricyclics
Anticonvulsants
Duloxetine
Other symptoms
Allodynia
•Plastic film
•Leg cradle at night
Restless legs
•Ropinirole
Painful Cramps
•Quinine sulphate
NICE CG 87
May 2009
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
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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?
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