1. www.plymouthdiabetes.org.uk/ Diabetic Neuropathy Patrick English Diabetes Consultant Derriford Hospital

2. www.plymouthdiabetes.org.uk/ Outline Size and costs of the problem Pathology/pathophysiology Risk factors Presentations Diagnosis Prevention and Treatment Algorithm/NICE

3. www.plymouthdiabetes.org.uk/ 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 2 nd line agent for pain 1. Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. Diabetologia 1993;36(2):150-4. 2. Caro, J. J., A. J. Ward, et al. (2002). Diabetes Care 25(3): 476-81.

4. www.plymouthdiabetes.org.uk/ Pathology Axonal loss, focal demyelination & regeneration  conduction velocity and  sensory thresholds

5. www.plymouthdiabetes.org.uk/ Pathophysiology-biochemical and vascular factors

6. www.plymouthdiabetes.org.uk/ Risk Factors Glycaemic control-DCCT  with age: 5% 20-29 years, 44.2% 70- 79 years > 50% T2DM >60 years of age  with duration of diabetes: 20.8% 10 years  Smoking  Microalbuminuria  Height ? Nutritional factors

7. www.plymouthdiabetes.org.uk/ 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

8. www.plymouthdiabetes.org.uk/ 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

9. www.plymouthdiabetes.org.uk/ 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

10. www.plymouthdiabetes.org.uk/

13. Autonomic Neuropathy 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

14. www.plymouthdiabetes.org.uk/

15. Diffuse Small Fibre Neuropathy T1DM Young, ♀ > ♂ Selective damage to small nerve fibres Pain and temp lost but LT retained Symptomatic autonomic neuropathy, Charcot arthropathy and foot ulcers ? autoimmune

16. www.plymouthdiabetes.org.uk/

17. Mononeuropathies Acute ? Secondary to ischaemia Pain and weakness (severe) Resolve over months  Amyotrophy (Older ♂>♀)  3 rd nerve  6 th nerve  Truncal radiculopathies

18. Diabetic Amyotrophy

19. www.plymouthdiabetes.org.uk/

20. Insulin Neuritis Acute & diffuse May be painful Follows improvement of blood glucose control ?steal phenomenon

21. www.plymouthdiabetes.org.uk/ 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

22. www.plymouthdiabetes.org.uk/

23. Pressure Palsies  susceptibility to pressure damage Limited joint mobility (soft tissue) Carpal tunnel Ulnar nerve Lateral popliteal nerve

24. www.plymouthdiabetes.org.uk/ 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

25. 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

26. www.plymouthdiabetes.org.uk/ Examination-ANS Ewing’s battery Abnormal results common Valsalva-expiration for 15 secs against 40 mmHg. Rest 1 min then repeatx2.  Avoid in proliferative retinopathy.  RR max : RR min>1.21 =Normal, <1.20 = abnormal. HR increase on standing  RR 30:15 ratio > 1.04  HR  at max overshoot or 15 seconds  15bpm (abnormal if<12)

27. www.plymouthdiabetes.org.uk/ Ewing’s battery HR variation during deep breathing (6 breaths per minute)  Max-min > 15bpm (<10 is abnormal) Postural BP-2 mins after standing  Fall< 10mmHg normal  >30 mmHg abnormal

28. www.plymouthdiabetes.org.uk/ Diagnosis Consider differential diagnoses HSMN Ethanol B12/folate Malignancy Renal failure Drugs AI disease Cord problems Leprosy

29. www.plymouthdiabetes.org.uk/ 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%  P=0.005  No protective effect seen for BP control

30. www.plymouthdiabetes.org.uk/ Prevention Aldose reductase inhibitors Gamma Linoleic Acid Vasodilators-ACE? AGE inhibitors Antioxidants NGFs ? Smoking cessation, ? BP reduction

31. 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

32. NICE CG 87 May 2009

33. www.plymouthdiabetes.org.uk/ Treatment -ANS Postural hypotension Fludrocortisone NSAIDs Compression stockings Elevate the head of the bed

34. www.plymouthdiabetes.org.uk/ Treatment -ANS Bladder Manual SP pressure ISC ? Anticholinesterase Cyclical antibiotics if recurrent infections Sweating ?clonidine Erectile dysfunction

35. www.plymouthdiabetes.org.uk/ 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

36. Any questions? www.plymouthdiabetes.org.uk