• Credits
  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

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• Q. What are the three main aspects of management of Diabetic neuropathy ?
  • Glycemic control
  • Foot care
  • Treatment of pain
• **Glycemic control **
• Q. Does glycemic control IMPROVE diabetic neuropathy?
  • This is an area of debate
  • Many studies including DCCT have shown objective improvement in glycemic control including improvement  in VPT and NCV
  • At present, however, it is believed that once established, diabetic neuropathy cannot be reversed and only progression can be halted by good glycemic control
• Q. What type of neuropathy can be corrected with glycemic control alone?
  • Acute painful diabetic neuropathy and rapidly reversible hyperglycemic neuropathy – can be corrected with glycemic control alone
  • However, in some cases, rapid improvement in glycemic control can lead to "insulin neuritis"
  • Hence stable glycemia is the aim not under or overtreatment
• **Foot care **
• Q. What are the components of foot care for diabetics?
  • Daily inspection of feet by patients
  • Physician inspection on regular visits
• **Management of painful diabetic neuropathy **
• Q. What are the points of difference between neuropathic pain from ischemic pain in diabetics?
  • 
• Q. Does the painful neuropathy spontaneously resolve?
  • In 55% of cases the pain resolves in 12 months
  • This is especially true if there is a recent change in glycemic status and there is a history of painful acute sensory neuropathy which is generally self-resolving
• #Pearl
  • Nerve may discharge spontaneously when it is either being damaged or being repaired
• Q. Does the pain disappear always a good sign?
  • Disappearance of pain can mean either there is improvement in the nerve function or deterioration
  • It is not always a good thing
• **Pain control **
• Q. Enlist the drugs used in the management of Painful diabetic neuropathy.
  • Antidepressants
    • Amitriptyline
    • Duloxetine
    • Venlafaxine
    • Desipramine
  • Anticonvulsants
    • Pregabalin
    • Gabapentin
    • Valproate
  • Others
    • Isorbidade dinitrate spray
    • Capsaicin cream
    • Alpha lipoic acid
    • TENS- transcutaneous electric nerve stimulation
• Q. Which are the three first-line agents in painful diabetic neuropathy?
  • SNRI- duloxetine, and venlafaxine
  • TCA- Amitryptiline , nortyptiline and desipramine
  • Gabapentinoid antiseizure medications - pregabalin , gabapentin
• Q. Of the above which is the best medication?
  • No medication is better than other
  • Hence the choice should depend on comorbidities, side effect profile, and patient preferences
• **Antidepressants **
• Q. Are antidepressants effective?
  • Yes
  • They have been proven in clinical trials
  • Effect is generally seen in 6 weeks and the dose required is less than the dose typically used in depression
• Q. What are the common side effects of amitriptyline and duloxetine?
  • Amitriptyline – Dry mouth
  • Duloxetine – constipation
• Q. What is the typical dose of amitriptyline used?
  • Starting dose of 10-25 mg
  • Can give up to 100 mg/day
  • Given at bedtime
• Q. In which patients do you need to be careful while prescribing TCA?
  • Patient with a history of heart disease
• Q. Which is the least cardiotoxic TCA?
  • Doxepin
• Q. Which TCA has fewer anticholinergic side effects?
  • Nortriptyline
• #Pearl
  • Also be careful of using amitryptiline in elderly males – as they can have urinary retention if they have a prostate problem. In patients with prostate issue, Amitryptiline can be replaced by nortriptyline
• Q. What is the action of Duloxetine?
  • It is a combination of SNRI and SSRI
• Q. What is the important side effect of duloxetine in diabetics?
  • It can cause a mild increase in blood glucose
• Q. What is the typical dose of Duloextine used?
  • Typically used in a dose of 60 mg
  • Starting dose of 20-30 mg - escalate up to 120 mg
  • Must be taken on a full stomach
• Q. Why is the drug not given on empty stomach?
  • It can cause nausea as an important side effect
• Q. Can it be combined with other SNRI?
  • No
  • But it can be combined with pregabalin
• Q. In which related condition, it must be avoided?
  • Avoid patients having restless leg syndrome since it can exacerbate the problem in such patients
• **Anticonvulsants **
• Q. What is the mechanism of action of Pregabalin?
  • Inhibits presynaptic release of excitatory neurotransmitters
• Q. What is a common but important side effect of Pregabalin?
  • Weight gain
  • Typically about 7% of weight gain is seen
  • Does not impact diabetes control
• Q. How do you dose pregabalin ?
  • Typical starting dose is 75-150 mg/day
  • Generally given in 2-3 divided doses
  • Most trials use a starting dose of 150 mg/day
  • Every 3-7 days, 75 mg dose can be increased to upto 300 mg/day
  • For other indications up to 600 mg/day is given, but for neuropathy 300 mg/day is generally sufficient
• Q. Is it a habit-forming drug?
  • Yes
• Q. Is gabapentin useful in painful diabetic neuropathy?
  • Yes. However, some trials have shown mixed results
  • Trials have shown it is not effective as placebo
  • It is typically given in a dose of 300-600mg TID
• Q. Which other anticonvulsants can be used?
  • Valproate and carbamazepine are effective but generally not used because of better drugs are available
• **Other drugs  **
• Q. What is the mechanism of action of Capsascian cream?
  • It causes local depletion of substance P
• Q. How and when is it used?
  • It is available as 0.075% cream
  • It is applied topically 4 times a day
  • Generally used if anticonvulsants and antiepileptics don’t work
• Q. What is the logic of using alpha lipoic acid (ALA) in DN?
  • ALA is an antioxidant
  • We know the role of reactive oxygen species in the etiology of DN
• Q. Which are the important trials with ALA?
  • SYDNEY 1 trial- IV ALA
  • SYDNEY 2 trial- use oral ALA
  • These trials have shown ALA to be effective
• Q. What is the dose of oral ALA to be used?
  • Oral ALA in a dose of 600 mg OD can be used in cases refractory to other medications
• Q. Which opioids have been used?
  • Tramadol
  • Oxycodone
  • Dextromethorphan
  • However, they are best avoided as they can cause addiction
• Q. Are combination treatments more effective than a single drug?
  • Yes
• Q. Is transcutaneous electric nerve stimulation useful?
  • Yes
  • TENS is useful for diabetic neuropathy
• Q. What about acetyl L carnitine?
  • Some trials have shown it to be effective in a dose of 1000 mg
• Q. Which spray is effective?
  • Isorbidade dinitrate spray
  • Small trials have shown it to be effective
• Q. What is the role of NSAIDs?
  • NSAIDs are effective in reducing pain in diabetic neuropathy
  • However, it can worsen nerve injury hence it is better avoided than other meds
• Q. Which procedure is used in refractory DN?
  • Spinal cord stimulation
  • It is an invasive procedure
  • Electrodes were introduced to give nerve stimulation to a dorsal column of the spinal cord
• Q. Which drug according to the American academy of neurology is most effective?
  • Pregabalin – in dose of 300-600 mg/day
• Q. What is the ADA approach?
  • 1st- Rule out non-diabetic etiology
  • 2nd - Stabilize blood glucose
  • 3rd- Tricyclic antidepressants / anticonvulsants
  • 4th- Opioid and other agents
• **Non-glycemic measures **
• Q. What is the role of surgical decompression?
  • It is known as Dellon’s procedure
  • It is the decompression of peripheral nerves as a treatment of painful diabetic neuropathy
  • However it is controversial and not recommended
• Q. Which anti-diabetic drug used in diabetes produces B12 deficiency?
  • Metformin
• Q. What B12 level is optimal in diabetic patients?
  • Generally -250 pg/ml
  • In diabetics – 460 pg/ml is the optimal B12 level
• Q. Which B12 preparation is better for diabetics?
  • Methylcobalamin Is better for diabetics, not cyanocobalamin
  • It is given in a dose of 3000 ug/day which achieves a B12 level of 1000 pg/ml
• Q. Which 2 conditions are often associated with painful Diabetic neuropathy ?
  • Mood disorder
  • Sleep disorder
  • Hence the treatment should address these issues as well
• Q. Apart from tramadol which is the other centrally acting opioid?
  • Tapentadol
  • It is available in India as TYDOL
  • 
• Q. Give a practical strategy for the management of painful diabetic neuropathy in India.
  • 
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