Diabetic peripheral neuropathy (DPN)

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

5. Statistics …

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 Place the vibrating fork on patient’s distal Hallux (big toe) joint and ask them if they can feel vibration 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? With diabetes, nerves suffer from hypoxia With diabetes, nerves form tumors. With diabetes, nerves split. All of the above

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

33. A serious consequence of untreated peripheral neuropathy is... Stroke Cancer Amputation 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