Diabetic Peripheral Neuropathy – Rueppel

Acute reversible neuropathy – associated with hyperglycemia and rapid correction of hyperglycemia.  Ex: DKA.  Improvement is ~50% chance, and can take up to a year to resolve.

Pathophysiology:  involves deposition of sorbitol?

 

Chronic persistent neuropathy:

  • Systemic polyneuropathy:  classic stocking-glove neuropathy; reduced or lost sensation on monofilament testing; burning or tingling.
  • Autonomic neuropathy:  smooth muscle; gastroparesis, postural hypotension, bladder dysfunction (urinary incontinence or retention), erectile dysfunction.

 

DDx of peripheral neuropathy:

  • Radiculopathy, spinal stenosis, vitamin B12 deficiency, toxins (EtOH, chemo), hypothyroidism, CRF, multiple myeloma (SPEP, UPEP), malignancies (bronchogenic carcinoma), HIV, CIDP…

 

Medications Used in Management:

  • Pregabalin:  presynaptically inhibits excitatory glutamate, substance P.
  • Duloxetine:  SSNRI – RCTs showed 59% vs 25% placebo; slightly more effective than pregabalin; take at QHS.
  • Amitriptyline:  dose =/= improvement; titrate patient-specific; average 105mg/day; alters central processing of pain; ~55% reduction in pain vs placebo; anticholinergic side-effects and QT prolongation.
  • Nortriptyline:  slightly less anticholinergic than amitriptyline; combine with gabapentin – works better than both alone.
  • Venlafaxine – likely not helpful.
  • Gabapentin – 300 – 900mg TID; doses > 1200mg/d more effective than smaller doses; some studies say it works better than placebo, some doesn’t.  Wide therapeutic window.
  • Valproic acid:  not in pregnancy; no RCTs to support.
  • Capsaicin: locally depletes substance P.
  • Alpha-lipoic acid:  anti-oxidant; RCTs show some benefit; ?reduces oxidative stress on nerve.
  • Lidocaine:  up to 4 x 5% patches for up to 18 hours.
  • TENS units:  daily tx x 30 minutes; desensitize nerves through stimulation; trials shows up to modest pain improvement after 6-12 weeks of treatment
  • Isosorbide dinitrite spray: topical spray, improves peripheral circulation
  • Acetyl-L-carnitine:  ?inhibits signals that causes senescence in cells; take with ALA – to counteract free radical formation, no data to support.
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