The presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes is called diabetic peripheral neuropathy. The diagnosis is principally a clinical one. Patients with type 1 diabetes for 5 or more years and all patients with type 2 diabetes should be assessed annually.Treatment goals include good glycemic control,symptomatic treatment and halt progressive nerve damage.

1. Diabetic peripheral
neuropathy
Insp Dr Mahadev Deuja
Wednesday, October 31, 2018

2. Outlines
 Introduction
 Epidemiology
 Anatomy of PNS
 Pathophysiology
 Clinical presentation
 Diagnosis
 Treatment
 Mcq’s

3. Introduction – what is DPN?
The presence of symptoms and/or signs of peripheral
nerve dysfunction in people with diabetes after
exclusion of other causes”

4. DPN :- statistics
≈70% of diabetics will lose sensation in their feet
Peripheral sensory neuropathy is the leading factor to diabetic foot
ulcerations
Approximately 25% of diabetics will develop a foot ulcer
More than half of all foot ulcers will become infected, requiring hospitalization and 1 in
5 will require an amputation
After a major amputation, 30% of patients will have their other limb
amputated within 3 years
5-year mortality rate after limb amputation is reported as high as 74%, when compared
to cancer- it is greater than colorectal, breast, and prostate cancer

5. Statistics …
More shocking is the fact that 75% of amputations are preventable
The estimated annual cost to treat diabetes related chronic
complications such as DPN is $58 Billion (US).
DPN is the most common type of neuropathy

6. Simplified view of PNS
 PNS consist of
 Large myelinated fibers, A alpha fibers
and A-beta fibers
 Thinly myelinated fibers (A-delta)
 Unmyelinated fibers, the C fibers.
 Large myelinated fibers
 Serve muscle control as well as touch,
vibration, and position perception.
 Smaller myelinated fibers
 Subserve cold thermal perception and
cold pain.

7. Cont…
 Thin unmyelinated fibers
 Subserve warm thermal perception and
pain.
 Autonomic nerve fibers or thin
myelinated fibers,
 Regulate heart rate, blood pressure,
sweating, and gastrointestinal and
genitourinary function.

8. Peripheral neuropathy
 Loss of nerve fiber function in the peripheral nerves
Normal nerve Abnormal nerve

9. Hyperglycemia Endoneurial Ischemia
Progressive Diabetic Peripheral Neuropathy
Neuronal Injury
Putative Pathogenic Sequence
Impaired Neuronal Regeneration

10. Symptoms of DPN
 Symptoms vary according to the class of nerve fibers
involved.
 The most common early symptoms are induced by
the involvement of small fibers and include
 Neuropathic pain
 May be the first symptom that prompts patients to seek
medical care
 Burning, lancinating, tingling, or shooting (electric
shock–like)
 Occurs with paresthesias
 Typically worse at night

11.  Neuropathic pain
 Accompanied by hyperalgesia(an exaggerated response to painful stimuli ) and allodynia (pain
evoked by contact, e.g., with socks, shoes, and bedclothes )
 Can lead to interference with daily activities, disability, psychosocial impairment, and
reduced health-related quality of life
 Symptoms are most commonly experienced in the feet and lower limbs, although in
some cases the hands may also be affected.
 Dysesthesias (unpleasant sensations of burning)

12.  The involvement of large fibers may cause numbness, tingling without pain, and
loss of protective sensation.
 Patients can also initially present with loss of sensation, numb foot due to the loss
of large fibers.
 Patients frequently state that their feet feel like they are wrapped in wool or they
are walking on thick socks.

13. Autonomic neuropathy
 Impairs the impaired vasoregulation
 May result in changes to the texture and turgor of the skin,
 causing the dryness and fissuring.
 Dryness predominantly effects the plantar foot.
 Dysregulation of local perspiration may contribute to increased
moisture and increase the risk of fungal infections.

14. Clinical tests
 The following clinical tests may be used to assess small- and large-
fiber function distal to proximal
 1. Small-fiber function: pinprick and temperature sensation
 2. Large-fiber function: vibration perception, proprioception, 10-g
monofilament, and ankle reflexes

15. Touch and pressure sensation screening
 Using the 10g Monofilament
 Assess the 4 main areas on the plantar surface of the foot
 i.e, the 1st, 3rd and 5th metatarsal heads and the plantar surface of the
hallux.
 Place the monofilament on each area of the foot
PERPENDICULARLY until the monofilament buckles, and hold for 2
seconds each time with the patient’s eyes closed
 The diagosis of neuropathy is determined if the patient does not feel
1 out of 4 areas tested.

16. Test for vibration loss
 128-Hz tuning fork is used
1. Place the vibrating fork on patient’s distal Hallux (big
toe) joint and ask them if they can feel vibration
2. If they cannot feel vibration on the hallux continue
checking bony prominences moving proximally until
the patient feels the vibration.

17. Test for temperature sensation
 With Tip-Therm or test tubes,
 One with cold water (5-10°C)
 One with warm water (35 to 45°C).

18. Check for ankle reflexes
 This may be weak in the elderly so it is not a
specific test

19. Diagnosis
 The diagnosis of DSPN is principally a clinical one.
 A combination of typical symptomatology and symmetrical distal sensory loss
Or
 Typical signs in the absence of symptoms in a patient with diabetes is highly
suggestive of DPN
 As up to half of the patients may be asymptomatic, a diagnosis may only be made
on examination or, in some cases, when the patient presents with a painless foot
ulcer.

20. DD’s
Nutritional
B12*
Pyridoxine
Thiamine
Tocopherol
Industrial agents
Acrylamide, Organophosphorous
agents
Drugs
Alcohol, Amiodarone, Colchicine,
Dapsone, Vinka alkaloids,
Platinum,Taxol
Metals
Arsenic, Mercury,
Hereditary
Hereditary motor, sensory, and
autonomic neuropathies
Metabolic disease
Thyroid disease (common)
Renal disease
Systemic disease
Systemic vasculitis
Nonsystemic vasculitis
Paraproteinemia (common)
Amyloidosis
Infectious
HIV
Hepatitis B
Lyme
Inflammatory
Chronic inflammatory demyelinating
polyradiculoneuropathy

21. DD’s
 Consider excluding neuropathy with causes other than diabetes
 By undertaking a family and medication history and performing relevant
investigations (e.g. serum B12, folic acid, thyroid function, complete blood count,
metabolic panel, and a serum proteinimmunoelectrophoresis).
 Electrophysiological testing or referral to a neurologist is rarely needed for
diagnosis, except in situations where the clinical features are atypical, the
diagnosis is unclear, or a different etiology is suspected
 Atypical features that warrant referral include motor greater than sensory
neuropathy, asymmetry of symptoms and signs, and rapid progression.

22. Screening
 Patients with type 1 diabetes for 5 or more years and all patients with type 2
diabetes should be assessed annually
 Using medical history and simple clinical tests.

23. Clinical Impact of DPN
DPN
Boulton A. NCVH. Oral Presentations. 2007.
Mortality
Cost
Impairment
Disability
Handicap
Infection
(skin, bone)
Charcot
Foot
Foot
Ulcers
Painful
Neuropathy
Quality of
Life
Sensory
Loss
Surgery,
Amputation

24. Treatment goals
 Good glycemic control
 Symptomatic treatment
 Halt progressive nerve damage

25. Treatment
 Currently available pharmacotherapies primarily consist of analgesics which
provide symptomatic pain control but do not affect the underlying causes of DPN
or its course.
 These include
 TCA
 Amitriptyline , desipramine, imipramine, nortriptyline, maprotiline)
 Anticonvulsants
 pregabalin, gabapentin , sodium valproate, carbamazepine, oxcarbazepine, lamotrigine,
topiramate, lacosamide),
 Serotonin norepinephrine reuptake inhibitors (venlafaxine)
 Opioids (tramadol, oxycodone, dextromethorphan, morphine)

26.  Only 2 medications are currently approved by the FDA for DPN, pregabalin and
duloxetine

27. Pregabalin
 Analog of GABA
 A calcium channel a2-d subunit ligand
 Has a more rapid onset of action and more limited dosage range that requires
minimal titration.
 Doses- 150 – 600mg/day

28. Duloxetine
 A selective norepinephrine and serotonin reuptake inhibitor.
 Doses of 60 and 120 mg/day showed efficacy in the treatment of pain associated
with DPN

29. Tapentadol
 Tapentadol extended release is a novel centrally acting opioid analgesic
 It exerts its analgesic effects through both m-opioid receptor agonism and
noradrenaline reuptake inhibition.
 Extended-release tapentadol was approved by the FDA for the treatment of DPN.
 Due to high risk for addiction and safety concerns compared with the relatively
modest pain reduction, it is not recommended as first- or second-line treatment.

30. Medical food: Mentax
 Nutritional support specifically modified for the management of the
distinct nutrient needs in DPN
 Regulated by FDA
 Combination of
 L- methylfolate 3mg;
 methylcobalamin 2mg:
 pyridoxal- 5’- phosphate 35mg (LMF – MC- P5P)
 Address some of the underlying pathophysiology of nerve function,
vascular function and endothelial function.
 Safety and efficacy demonstrated in peer- review literature
 Found to reduce pain associated with DPN

31. Mcq’s
 How are nerves damaged from diabetes?
1. With diabetes, nerves suffer from hypoxia
2. With diabetes, nerves form tumors.
3. With diabetes, nerves split.
4. All of the above

32.  Why is diabetes troublesome for the feet?
1. Diabetic nerve pain can cause numbness in the feet.
2. Diabetes can deprive feet of nutrients and oxygen.
3. Diabetes increases the risk for infections, ulcers, and injuries.
4. All of the above

33.  A serious consequence of untreated peripheral neuropathy is...
1. Stroke
2. Cancer
3. Amputation
4. All of the above

34. Refrences
 Available at: http://care.diabetesjournals.org/content/diacare/40/1/136.full.
Accessed September 22, 2017.
 Federation ID. Managing Older People with Type 2 Diabetes, Global Guideline.
2013.
 emedicine.com. Accessed October 3, 2018].
 Available at: http://www.hyprocure.com/. Accessed October 3, 2018.
 https://www.medscape.org/viewarticle/747552
 Kasper D, Fauci A, Hauser S et al. Harrison's Principles of Internal Medicine 19/E
(Vol.1 & Vol.2). McGraw Hill Professional; 2015.

35. Thank you