1. PROF. AR ALTAHAN FRCP NEUROLOGY DIVISION KKUH
DIABETIC NEUROPATHY
PROF. AR ALTAHAN FRCP
NEUROLOGY DIVISION
KKUH

2. Diabetic Neuropathy Common long term complication
54% type 1 & 45% in type 2
(Dyck et al 93)

3. Diabetes Mellitus
Diabetes Mellitus is one of the most common chronic health problems in Saudi Arabia
23.7%  overall prevalence
36.5%  above 60 yrs old
(Alnozha et al 2004)
Other risk factors; Hb A1c, also Duration  Sosenko et al 85.
male ,also age &duration-- DCCT 90
Microangiopathy—Neuropathy,Retinopathy&Nephropathy more common in IDDM
Macroangiopathy---NIDDM.. cause of death in 50-60% of NIDDM

4. Diabetic Neuropathy Associated with increased morbidity & mortality
Sever neuropathy in ~25% :
estimated 450,000 patients in Saudi Arabia
Consider limitation of DN definition ..& severity…

5. Diabetic Neuropathy Associated with increased morbidity & mortality
Sever neuropathy  increased debilitating complications.
Increased Risk of silent MI & sudden death
Consider limitation of DN definition ..& severity…

6. Diabetic Neuropathy Clinical Features
Multiple clinical pictures, reflecting multiple etiologies

7. Classification Of DN (Dyck 1993)
Polyneuropathy ..Sensory
Focal & Multifocal ..Motor

8. Distal Sensory DN The commonest type of DN (80%)
Symmetric & distal distribution
Mainly sensory & painless:
Numbness, tingling, tightness
walking on cotton-wool…etc.
Painful in 10%:
Burning…aching…sharp quality
Associated with….Retinopathy & Nephropathy
( Not other types of DN) Evidences of a common pathogenesis:
1- Statistically associated
2- Similar microvascular functional and structural changes
3-Glycemic control- same preventive effect
No selectivity in sever DN ( Said et al )
Others….. Small fibers are more vulnerable….Early small fibers…Later.. Mixed
Psuedosyringomyelia vergly1895…………Pseudotabes Chust 1898
GBS…….CMV—sensory
Campylobacter J Motor

9. Distal Sensory DN Risk factors for developing distal DN : Age
Duration of DM
Diabetic control
Male & height (DCCT 90)

10. Distal Sensory DN Complications
Diabetic Foot
Neurogenic Arthropathy
Autonomic Neuropathy
Other risk factors; Hb A1c, also Duration  Sosenko et al 85.
male ,also age &duration-- DCCT 90
Microangiopathy—Neuropathy,Retinopathy&Nephropathy more common in IDDM
Macroangiopathy---NIDDM.. cause of death in 50-60% of NIDDM

11. Diabetic Foot Clinical Features
Numbness, hair loss, dry skin
Painless ulcers
Osteomyelitis, cellulitis, & abscess
Gangrene & Amputation

13. Diabetic Foot Pathophysiology
Sensory loss & autonomic changes
Small vessel disease-Ischemia
Trauma (foreign body)
Infection

14. Neurogenic Arthropathy
Severe loss of pain sensation & painless ulcers
Enhanced by trauma & abnormal posture
XR : painless fractures-disorganization of ANKLES

16. Autonomic Neuropathy Correlates with severity of distal sensory DN
Associated with poor prognosis
50 % reduction of 5 yrs survival
Increased sudden death & silent MI

17. Autonomic Neuropathy Clinical Manifestations
Postural hypotension:
BP drop >20 mmHg
Bladder atony (Overflow incontinence)
Gastro-intestinal paresis
(Fullness & diabetic diarrhea)
Impotence

18. Autonomic Neuropathy ..Clinical Manifestations
Heat intolerance
Unawareness of hypoglycemia
Impaired hypoglycemia counter- regulation

19. RR variations in DN

20. Focal & Multifocal neuropathies
Acute or Subacute onset
Predominantly Motor
Spontaneous recovery
(Improve control)

21. Focal & Multifocal neuropathies
Cranial Neuropathies
Entrapment Neuropathies
(Carpal Tunnel Syndrome)
Diabetic amyotrophy

23. DN Pathogenesis Multifactorial
Metabolic
Vascular
Others

24. DN Pathogenesis Metabolic Hypothesis
Sorbitol accumulation
Non-enzymatic glycation
Oxidative stress
Others
Evidence of Multi-factors involved. Earlier studies. + effect of : Glycemic control, Aldos Reductase Inhibitor, Myoinositol, Gamma Linoleic Acid. + peroneal nerve CV…Also non-specific neural stimulant..: Gangliosides.
Increased oxidative load ( free radicals excess ) ????

25. DN Pathogenesis Vascular Hypothesis
Early endoneural hypoxia
 Metabolic changes & Microangiopathy & Ischemia
Vasodilators attenuates it in Experiments.
Low et al; endoneural hypoxia  increased Resistance to Ischemic Conduction Failure

26. Treatment Of Diabetic Neuropathy

27. Cornerstone  Tight control
Treatment Of DN
Cornerstone  Tight control
IIT  64% risk reduction of developing DN over 5 yrs (DCCT 93)
SC Insulin infusion (Service et al 85).
Pancreatic transplant (Kennedy et al 90).
Improve early CV slowing (Green et al 84)
Improve early CV slowing Neuropathy, Nephrpathy,Retinopathy…. related to Microvascular disease.
In NIDDM…Risk moltifactorial ..Death is mainly due to Macrovascular disease. Additional Risk factors needs attention.

28. Analgesia Tricyclic anti-depressants
Anti-epileptics ( Carbamazepine & Gabapentin, Pregabalin)
Opioids (Tramadol)
Amitriptyline..Imipramine……dose dependent……
Gabapentin…… ……Gabapentin=Amitriptylline rand.double blind study (Morello 99)
Tramadol……non-narcotic..Opioids-like analgesic Short term usage—GI dist.
Mexiletine…++ in painful DN,no serious cardiac side effects for 3 weeks.

29. Analgesia Topical Lidocain patch Clonidin patch
Capsaicin  aching pains
Nerve and Spine stimulators
Acupuncture
Clonidine…Patches
Capsaicin..Active ingredient in red pepper…deplete substance P..Modest, adjunct therapy in certain patients.
Cholinergic channel modulator ( ABT-594 ).. Promising in treatment of chronic pains.Oral & Parenteral