Brief review of diabetic neuropathy and its management

1. Diabetic Neuropathy
Dr Muhammad Khurram
FCPS, FRCP

7. Diabetes Mellitus
• What is DM
• DM is an increasingly serious social, economic
and medical threat that is not just a health
issue, but a development issue (as it hinders
progress).

8. DM Figure Wise
• World Total 366 + million
• Pakistan currently 7.1 + million
• % Population 7-9%
• By 2030 11.4 + million
• Death toll/year 88000

9. Diabetic Neuropathy
• The San Antonio Consensus Statement on
Diabetic Neuropathy defined the condition as
being a demonstrable disorder, either
clinically evident or subclinical in the setting of
diabetes without other causes of peripheral
neuropathy.

10. • 50-90% of patients who have diabetes also
has neuropathy
• 22.7% DM I, 32.1% DM II
• 11-32% of patients with Diabetic Neuropathy
experience painful symptoms

11. Risk Factors
• Glycaemic control
•  with age
– 5% 20-29 years 44.2% 70-79 years
– 50% T2DM >60 years of age
•  with duration of diabetes
– 20.8% < 5years 36.8%>10 years
•  Smoking
•  Microalbuminuria
• Height
• Nutritional factors, additional illnesses

12. Pathogenesis
• Increased aldose reductase activity.
• Auto oxidation of glucose
• Non enzymatic glycation of protein(AGE)
• Activation of protein kinase C
• Oxidative stress
• Decrease essential fatty acid
• Reduced serum levels of nerve growth factor
• Nerve ischemia/hypoxia.

14. • Axonal loss
• Focal demyelination & regeneration
• Intraneural capillary abnormalities
•  conduction velocity and  sensory
thresholds

15. Classification
• Somatic
– Polyneuropathy
• Symmetrical, mainly sensory and distal
• Asymmetrical, mainly motor and proximal
– Mononeuropathy & MNM
• Visceral
– GIT, CVS, Genitourinary
– Vasomotor, sudomotor, pupillary

16. Clinical Features
• Alone or combination
• Occur as the disease duration increases and
depend on glycemic control generally
• Acute and rapid
• Slow and progressive

17. Symmetrical Mainly Sensory DPN
• Asymptomatic
• Symptomatic
– Paresthesia
– Pain
– Burning sensations
– Hyperaesthesia
– Gait
– Small muscle wasting
– Charcot Joint

18. Asymmetrical Motor DN
• Severe, progressive weakness of proximal
muscles
• Predominant LL involvement
• Pain
• Neuropathic cahexia
• Upgoing planters and depressed refelexes
• Outcome

19. Mononeuropathy & MNM
• Peripheral/cranial nerve involvement
• Motor, sensory or both components
• Sudden and rapid onset
• Good recovery
• 3rd, 6th, Femoral/Sciatic nreves
• Truncal radiculopathies
• Entrapment neuropathies
– Median, Ulnar, Lateral popliteal
– AGE of tissues and Neuropathy

20. Autonomic DNP
• Different- relation with glycemia control
• Sympathetic or parasympathetic predominance
• Poor outcome
• CVS
– Postural hypotension, resting tachycardia, fixed heart
rate
• GIT
– Dysphagia
– Nausea, vomiting, distension, bloating,
– Diarhea, incontinencnce
– Constipation

21. • Uinary
– Difficulty in micturation, incontinence, recurrent
infection
• Sudomotor
– Sweating, Anhidrosis, Gustatory sweating
• Vasomotor
– Cold feet, Edema, Bullae
• Pupillary
– Meiosis, mydriatic resistance, reflex abnormality

22. • Erectile dysfunction
– Multifatorial
– Neuropathy, vascular, psychological, endocrine, Rx

23. How to diagnose
• History
• Clinical Examination
• Investigations
– General Investigations
– Imaging
– NCS
– Biopsy

24. AN Tests
• Resting heart rate
– >100/m is abnormal.
• Systolic BP response to standing
– BP measured supine. Patient stands, BP aft 2 m.
– Normal response- fall of <10 mmHg,
– Borderline - fall of 10–29 mmHg
– Abnormal - fall of >30 mmHg with symptoms

25. • Beat-to-beat HRV
– At rest and supine heart rate by ECG while patient
breathes at 6/m
– Difference of >15 bpm - normal, <10 bpm -
abnormal.

26. • Heart rate response to the Valsalva manoeuvre
– Exhales into manometer to 40 mmHg for 15 seconds
– Healthy subjects develop tachycardia & peripheral
vasoconstriction during strain & overshoot bradycardia,
rise in BP with release.
– The ratio of longest R-R to shortest R-R should be ≥1.2.

27. • Neurovascular flow
– Using noninvasive laser Doppler measures of
peripheral sympathetic responses to nociception.
• Radionuclide Cardiac Imaging
– MIBG
– 11-C-hydroxyephedrine

28. Tips
• Duration of illness
• Glycemia control
• Other complications
• Symptoms
• Clinical evaluation

29. Management
• Glycemia assessment and control
• Exclusion of other causes
• Risk factors modifications
• Specific measures

32. Exclusion of other causes/Risk factor
modification
• Vitamin deficiencies
• Malignant disease (e.g., bronchogenic
carcinoma)
• Metabolic
• Toxic (e.g., alcohol)
• Infective/post infection
• Medications

33. Specific Measures
• Pain and paresthesias
– Anticonvusants (gabapentin, pregabalin,
carbamezapine, phenytoin)
– TCA (amitryptaline, nortriptaline)
– Duloxetine
– Capsaicin
– Opiates
– Memrane stabilizers (mexilitine)
– Antioxidants

34. • Postural hypotension
– Compression stocking
– NSAIDS
– Fludrocortisone
• Gastroparesis
– Dopamine antagonisits
– Erythromycine
– Jejunal feeding, Pacing

35. • Diarrhea
– Loperamide
– Abx
– Octreotide
– Clonidine
• Constipation
– Laxative
• Bladder atony
– Catheterisation

36. • Excessive sweating
– Oxybutinin, propantheline
– Clonidine
– Glycopyrolate
• Erectile dysfunction
– Sildenafil, verdenafil, tadalafil
– Dopamine agunsist- apomorphine SL
– PGE1- Alprostadil
– Vacuum devices, implants
– Psychosexual therapy

37. Take Home Message
• Diabetic neuropathy is common
• Metabolic & vascular factors cause it.
• Distal symmetrical sensorimotor polyneuropathy is
commonest form
• Non DM aetiologies need exclusion
• Should be sought
• Optimal glycemic control is required
• Other DM issues should be managed
• Focused care and medications are required

38. THANX A LOT