Guideline sources The following summarized guidelines for the evaluation and management of diabetic neuropathy are prepared by our editorial team based on guidelines from the American Diabetes Association (ADA 2023), the American Academy of Neurology (AAN 2022; 2010), the Diabetes Canada Guidelines (Diabetes Canada 2018), and the European Federation of Neurological Societies (EFNS 2010). 1 2 3 4 5 6 7 8 8 8 Definition Diabetic neuropathy is a type of neuropathy that occurs due to microvascular disease and chronic hyperglycemia in diabetic patients. 6 Epidemiology Diabetic neuropathy is caused by persistent hyperglycemia, microvascular insufficiency, oxidative and nitrosative stress, defective neurotropism, and autoimmune-mediated nerve destruction in patients with diabetes mellitus. 8 Pathophysiology The incidence of diabetic neuropathy is estimated at 17.8 per 100,000 person-years in the United Kingdom. 7 Di https://web.pathway.md/diseases/recPepuIukRLfRplP 1/6 6/29/23, 10:16 PM Diabetic neuropathy Pathway Disease course Nerve damage leads to hyperalgesia, dysesthesia, allodynia, weakness, numbness, hypoalgesia, anomalies in thermal sensation and autonomic function, foot ulcerations, gangrene, and amputations. 8 Prognosis and risk of recurrence Diabetic neuropathy is associated with a 1.7-12-fold higher risk of amputation. In addition, autonomic neuropathy is associated with a mortality rate of approximately 25-50% at 5-10 years. 8 Pathway Diabetic neuropathy Diagnosis and management Guidelines 1. Screening and diagnosis Indications for screening: As per ADA 2023 guidelines, screen for diabetic peripheral neuropathy starting at diagnosis of T2DM and 5 years after the diagnosis of T1DM, and at least annually thereafter. B As per AAN 2022 guidelines, assess patients with diabetes for peripheral neuropathic pain and its effect on the patient's function and quality of life. B As per Diabetes Canada 2018 guidelines: Screen for peripheral neuropathy in patients with T2DM at diagnosis and annually thereafter. B Screen for peripheral neuropathy in patients with T1DM annually starting 5 post-pubertal years after diagnosis. B 2. Diagnostic investigations Clinical assessment: As per ADA 2023 guidelines: Elicit a careful history and assess either temperature or pinprick sensation (small fiber function) and vibration sensation using a 128-Hz tuning fork (for large-fiber function) for the assessment of distal symmetric polyneuropathy. Obtain annual 10-g monofilament testing in all patients with diabetes to identify feet at risk for ulceration and amputation. B Assess for symptoms and signs of autonomic neuropathy (orthostatic dizziness, orthostatic hypotension, syncope, resting tachycardia, or dry cracked skin in the extremities) starting at diagnosis and at least annually thereafter in patients with evidence of other https://web.pathway.md/diseases/recPepuIukRLfRplP 2/6 6/29/23, 10:16 PM Diabetic neuropathy Pathway microvascular complications, particularly kidney disease and diabetic peripheral neuropathy. B As per Diabetes Canada 2018 guidelines, screen for peripheral neuropathy by assessing loss of sensitivity to the 10-g monofilament or loss of sensitivity to vibration at the dorsum of the great toe. A Psychosocial assessment: assess patients with painful diabetic neuropathy for the presence of concurrent mood and sleep disorders and treat them as appropriate. B 3. Medical management Glycemic control: As per ADA 2023 guidelines, optimize glucose control to slow the progression of neuropathy in patients with T2DM. B As per Diabetes Canada 2018 guidelines, optimize glycemic control to slow the progression of neuropathy in patients with T1DM A and T2DM. B Systemic therapy: As per ADA 2023 guidelines, offer gabapentinoids, SNRIs, TCAs, and sodium channel blockers as initial treatment for neuropathic pain in patients with diabetes. A Refer to a neurologist or pain specialist if pain control is not achieved within the scope of practice of the treating physician. B As per AAN 2022 guidelines, take into consideration factors other than efficacy, given similar efficacy, including potential adverse effects, patient comorbidities, cost, and patient preferences, when initiating pharmacologic treatment in patients with painful diabetic neuropathy. B Show 4 more As per Diabetes Canada 2018 guidelines: Consider offering the following agents, alone or in combination, for the treatment of patients with painful peripheral neuropathy: gabapentin C or pregabalin B valproate C amitriptyline C duloxetine or venlafaxine. C Consider offering opioid analgesics (tramadol, tapentadol ER, oxycodone ER), taking into account the risks of abuse, dependency, and tolerance, in patients not responding to the above agents. C As per EFNS 2010 guidelines, offer any of the following agents as first-line therapy in patients with painful polyneuropathy: TCAs gabapentin or pregabalin SNRIs (duloxetine, venlafaxine). A Show 2 more Topical therapy: https://web.pathway.md/diseases/recPepuIukRLfRplP 3/6 6/29/23, 10:16 PM Diabetic neuropathy Pathway As per AAN 2022 guidelines, consider offering topical therapy (capsaicin, glyceryl trinitrate spray, Citrullus colocynthis) in patients preferring topical interventions. C As per Diabetes Canada 2018 guidelines, consider offering topical nitrate spray, alone or in combination with systemic therapy, for the treatment of patients with painful peripheral neuropathy. C Management of inadequate response: view an individual intervention as a failure either when the medication has been titrated to a demonstrated efficacious dose for approximately 12 weeks without clinically significant pain reduction or when side effects from the medication outweigh any benefit in reduced neuropathic pain. B Show 2 more 4. Nonpharmacologic interventions Psychosocial interventions: consider offering CBT and exercise in patients preferring nonpharmacologic interventions. C Alternative and complementary medicine: consider offering Ginkgo biloba, Tai Chi, or mindfulness in patients preferring nontraditional interventions. C Footwear: offer specialized therapeutic footwear in high-risk patients with diabetes, including patients with loss of protective sensation, foot deformities, ulcers, callous formation, poor peripheral circulation, and a history of amputation. B 5. Therapeutic procedures Transcutaneous electrical nerve stimulation: consider offering electric nerve stimulation in patients with painful diabetic neuropathy. C 6. Patient education General counseling: counsel patients that the goal of pharmacologic therapy for painful diabetic neuropathy therapy is to reduce, and not necessarily eliminate, pain. B Show 2 more 7. Preventative measures Primary prevention: As per ADA 2023 guidelines, optimize glucose control to prevent or delay the development of neuropathy in patients with T1DM. B As per Diabetes Canada 2018 guidelines, optimize glycemic control to prevent the onset of neuropathy in patients with T1DM A and T2DM. B Clinical findings https://web.pathway.md/diseases/recPepuIukRLfRplP 4/6 6/29/23, 10:16 PM Diabetic neuropathy Pathway Symptoms Past medical history Bloating Diabetes mellitus Burning sensation of feet Diabetic foot Burning sensation of hands Diabetic nephropathy Constipation Diabetic retinopathy Diarrhea Dyslipidemia Difficulty walking Hypertension Early satiety Obesity Erectile dysfunction Orthostatic hypotension Exercise intolerance Poorly controlled diabetes Fecal incontinence Vascular exam Foot pain Hand pain Lower extremity ulcer Loss of appetite Integument exam Nausea Numbness of feet Hypohidrosis Numbness of hands Skin dryness Urinary incontinence Vomiting Social history Tobacco use Neurological exam Hyperesthesia Inability to wALK on heels light touch perception pinprick sensation vibration sensation Lab findings Hyperglycemia References 1. Steven E. Kahn, Cheryl A.M. Anderson, John B. Buse et al. Standards of Care in Diabetes 2023. Diabetes Care. 2023 Jan;46 Supplement_1 S1 S291. Open 2. Raymond Price, Don Smith, Gary Franklin et al. Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary: Report of the AAN Guideline Subcommittee. Neurology. 2022 Jan 4;98 1 31 43. Open 3. Diabetes Canada Clinical Practice Guidelines Expert Committee, Bril V, Breiner A et al. Neuropathy. Can J Diabetes. 2018 Apr;42 Suppl 1 S217 S221. Open 4. Dubinsky RM, Miyasaki J. Assessment: efficacy of transcutaneous electric nerve stimulation in the treatment of pain in neurologic disorders (an evidence-based review): report of the Therapeutics and https://web.pathway.md/diseases/recPepuIukRLfRplP 5/6 6/29/23, 10:16 PM Diabetic neuropathy Pathway Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010 Jan 12;74 2 173 6. Open 5. N Attal, G Cruccu, R Baron et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010 Sep;17 9 1113-e88. Open 6. Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neuropathy. F1000Res. 2016 Apr 25;5. pii: F1000 Faculty Rev-738. Open 7. Reed C, Hong J, Novick D et al. Incidence of diabetic peripheral neuropathic pain in primary care - a retrospective cohort study using the United Kingdom General Practice Research Database. Pragmat Obs Res. 2013 Sep 27;4 27 37. eCollection 2013. Open 8. Vinik AI, Nevoret ML, Casellini C et al. Diabetic neuropathy. Endocrinol Metab Clin North Am. 2013 Dec;42 4 747 87. Open 9. Richardson JK. The clinical identification of peripheral neuropathy among older persons. Arch Phys Med Rehabil. 2002 Nov;83 11 1553 8. Open 10. Kanji JN, Anglin RE, Hunt DL et al. Does this patient with diabetes have large-fiber peripheral neuropathy?. JAMA. 2010 Apr 21;303 15 1526 32. Open 11. American Diabetes Association. Standards of Medical Care in Diabetes-2019 Abridged for Primary Care Providers. Clin Diabetes. 2019 Jan;37 1 11 34. Open 12. American Diabetes Association. 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes 2019. Diabetes Care. 2019 Jan;42 Suppl 1 S124 S138. Open 13. American Diabetes Association Professional Practice Committee, American Diabetes Association Professional Practice Committee:, Draznin B et al. Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45 Supplement_1 S1 S264. Open https://web.pathway.md/diseases/recPepuIukRLfRplP 6/6