Diabetic Neuropathy

Last Updated: November 18, 2022

Diabetic neuropathy is damage to nerves and blood vessels caused by high blood glucose in diabetes. Damage to nerves can cause numbness in the hands, legs, and feet, urinary problems, sexual dysfunction, dizziness, and sharp, burning, or tingling sensations.

Diabetic Neuropathy falls under theDiabetes & Blood SugarandPaincategories.

What is diabetic neuropathy?

Diabetic neuropathies are a group of conditions that damages the nervous system of people with diabetes mellitus. They include distal symmetric polyneuropathy, diabetic peripheral neuropathy, diabetic autonomic neuropathy, cardiac autonomic neuropathy, and gastrointestinal neuropathies. These neuropathies can damage nerves and impair normal function in several organ systems, including the musculoskeletal system (especially the lower limbs and feet), the cardiovascular system, the gastrointestinal system, and the urogenital system (kidneys, bladder, and genitals). Distal symmetric polyneuropathy is the most common form of diabetic neuropathy, affecting the lower limbs and feet.[1][2] Consequently, diabetic neuropathies reduce a person’s quality of life.

What are the main signs and symptoms of diabetic neuropathy?

Diabetic neuropathies have several non-specific signs and symptoms that are also caused by other conditions. Therefore, diabetic neuropathy can go undiagnosed and untreated. Symptoms include numbness and tingling (paresthesia) in the fingers and toes, pain in the lower legs and feet, foot ulcers, lightheadedness/dizziness when standing up, erectile dysfunction, and gastrointestinal issues such as nausea, bloating, heartburn, diarrhea, and constipation.[1][2] The signs are revealed with diagnostic tests showing poor nerve function (e.g., inability to sense a pinprick), impaired sensations (e.g., inability to distinguish hot from cold), orthostatic hypotension (a drop in blood pressure when standing up), resting tachycardia (high resting heart rate), and delayed gastric emptying (gastroparesis).[1][2]

How is diabetic neuropathy diagnosed?

People who’ve had type 1 diabetes for at least five years, and all people with type 2 diabetes, are typically assessed annually for diabetic neuropathies.[1][2] Assessment includes clinical tests exploring a person’s sensations of vibration, thermal changes, and pain.[1][2] But, since diabetic neuropathies are a collection of several conditions with non-specific signs and symptoms, and since nondiabetic neuropathies can also occur in people with diabetes, the diagnosis of diabetic neuropathy is a process of exclusion — i.e., alternative causes of the presenting signs and symptoms are systematically ruled out before a final diagnosis.

What are some of the main medical treatments for diabetic neuropathy?

There are no specific treatments for nerve damage, but lowering hyperglycemia (persistently high blood glucose concentrations) reduces the risk of diabetic neuropathy.[3][4][5] Therefore, the main treatment is to improve blood glucose control using lifestyle behavior change (diet, exercise, and weight management counseling) and glucose-lowering drugs.[1][2] 

Since diabetic neuropathies can impair sensation, healthcare providers regularly examine patients’ feet for signs of damage to help prevent diabetic foot ulcers. To treat pain associated with diabetic neuropathies, pain-reducing medications (e.g., pregabalin or duloxetine) are used to improve quality of life.[6][7] Reducing pain also helps patients increase their levels of daily physical activity, which improves blood glucose control.[8]

Have any supplements been studied for diabetic neuropathy?

Yes, research has examined the effects of several supplements on diabetic neuropathy. These include vitamin D, vitamin B12, L-carnitine, alpha-lipoic acid (ALA), and more.[9][10][11][12][13][14] However, additional high-quality randomized controlled trials are needed to make firm conclusions concerning the effectiveness of supplements in reducing the risk of diabetic neuropathy or relieving its symptoms (e.g., pain).

How could diet affect diabetic neuropathy?

Lifestyle behavior change improves blood glucose control in people with diabetic neuropathies.[1][2] This includes an individualized diet to help patients lose weight and minimize postprandial (after-meal) rises in blood glucose concentrations.

Specific micronutrients might also play a role. For example, deficiencies in vitamin D [15][16][17][18] and vitamin B12 [19] are associated with an increased risk of diabetic neuropathy. Therefore, people with diabetes who don’t consume vitamin D-containing foods (oily fish, egg yolks, liver, etc.), or who eat a plant-based diet that excludes meat, might be at a greater risk of diabetic neuropathy. However, studies are needed to test these hypotheses.

Are there any other treatments for diabetic neuropathy?

Aerobic exercise and sensorimotor training to improve motor control (balance, posture, etc.) can relieve some of the signs and symptoms of diabetic peripheral neuropathy.[20] Furthermore, low-frequency electrical stimulation of the spinal cord (also known as neuromodulation therapy) can reduce pain associated with diabetic neuropathies.[21][22] However, more high-quality randomized controlled trials are needed to draw conclusions about the efficacy and safety of neuromodulation therapy.

What causes diabetic neuropathy?

The exact causes are unclear. Current evidence suggests that hyperglycemia and hyperlipidemia (persistently high blood glucose and lipids) drive neuronal oxidative stress and chronic low-grade inflammation, leading to nerve damage. [26][23][27]

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  1. ^, Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, Freeman R, Green J, Huang E, Isaacs D, Kahan S, Leon J, Lyons SK, Peters AL, Prahalad P, Reusch JEB, Young-Hyman D12. Retinopathy, Neuropathy, and Foot Care: Standards of Medical Care in Diabetes-2022.Diabetes Care.(2022-01-01)
  2. ^Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler DDiabetic Neuropathy: A Position Statement by the American Diabetes Association.Diabetes Care.(2017-01)
  3. ^Callaghan BC, Little AA, Feldman EL, Hughes RAEnhanced glucose control for preventing and treating diabetic neuropathy.Cochrane Database Syst Rev.(2012-Jun-13)
  4. ^Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E, Leonetti F, Fallucca FExercise training can modify the natural history of diabetic peripheral neuropathy.J Diabetes Complications.(2006)
  5. ^Tatikola SP, Natarajan V, Desai VK, Asirvatham AR, Rajsekhar HEffect of various exercise protocols on neuropathic pain in individuals with type 2 diabetes with peripheral neuropathy: A systematic review and meta-analysis.Diabetes Metab Syndr.(2022-Sep)
  6. ^Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace MPharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.Lancet Neurol.(2015-Feb)
  7. ^Griebeler ML, Morey-Vargas OL, Brito JP, Tsapas A, Wang Z, Carranza Leon BG, Phung OJ, Montori VM, Murad MHPharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis.Ann Intern Med.(2014-Nov-04)
  8. ^Umpierre D, Ribeiro PA, Kramer CK, Leitão CB, Zucatti AT, Azevedo MJ, Gross JL, Ribeiro JP, Schaan BDPhysical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis.JAMA.(2011-May-04)
  9. ^Yammine K, Wehbe R, Assi CA systematic review on the efficacy of vitamin D supplementation on diabetic peripheral neuropathy.Clin Nutr.(2020-10)
  10. ^Farah S, Yammine KA systematic review on the efficacy of vitamin B supplementation on diabetic peripheral neuropathy.Nutr Rev.(2022-04-08)
  11. ^Jayabalan B, Low LLVitamin B supplementation for diabetic peripheral neuropathy.Singapore Med J.(2016-Feb)
  12. ^Khalil H, Ang CD, Khalil VVitamin B for treating diabetic peripheral neuropathy - A systematic review.Diabetes Metab Syndr.(2021)
  13. ^Rolim LC, da Silva EM, Flumignan RL, Abreu MM, Dib SAAcetyl-L-carnitine for the treatment of diabetic peripheral neuropathy.Cochrane Database Syst Rev.(2019-06-15)
  14. ^Abubaker SA, Alonazy AM, Abdulrahman AEffect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review.Cureus.(2022-Jun)
  15. ^Yammine K, Abi Kharma J, Kaypekian T, Assi C, Zeeni NIs diabetic neuropathy associated with vitamin D status? A meta-analysis.Br J Nutr.(2022-04-14)
  16. ^Lv WS, Zhao WJ, Gong SL, Fang DD, Wang B, Fu ZJ, Yan SL, Wang YGSerum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis.J Endocrinol Invest.(2015-May)
  17. ^Qu GB, Wang LL, Tang X, Wu W, Sun YHThe association between vitamin D level and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: An update systematic review and meta-analysis.J Clin Transl Endocrinol.(2017-Sep)
  18. ^Zhang B, Zhao W, Tu J, Wang X, Hao Y, Wang H, Zhao Y, Mizuno K, Tseng Y, Bu HThe relationship between serum 25-hydroxyvitamin D concentration and type 2 diabetic peripheral neuropathy: A systematic review and a meta-analysis.Medicine (Baltimore).(2019-Nov)
  19. ^Stein J, Geisel J, Obeid RAssociation between neuropathy and B-vitamins: A systematic review and meta-analysis.Eur J Neurol.(2021-06)
  20. ^Streckmann F, Balke M, Cavaletti G, Toscanelli A, Bloch W, Décard BF, Lehmann HC, Faude OExercise and Neuropathy: Systematic Review with Meta-Analysis.Sports Med.(2022-05)
  21. ^D'Souza RS, Langford B, Dombovy-Johnson M, Abd-Elsayed ANeuromodulation Interventions for the Treatment of Painful Diabetic Neuropathy: a Systematic Review.Curr Pain Headache Rep.(2022-May)
  22. ^Duarte RV, Nevitt S, Maden M, Meier K, Taylor RS, Eldabe S, de Vos CCSpinal cord stimulation for the management of painful diabetic neuropathy: a systematic review and meta-analysis of individual patient and aggregate data.Pain.(2021-11-01)
  23. ^Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman ELDiabetic neuropathy: clinical manifestations and current treatments.Lancet Neurol.(2012-Jun)
  24. ^Cai Z, Yang Y, Zhang JA systematic review and meta-analysis of the serum lipid profile in prediction of diabetic neuropathy.Sci Rep.(2021-01-12)
  25. ^Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH,Vascular risk factors and diabetic neuropathy.N Engl J Med.(2005-Jan-27)
  26. ^Baum P, Toyka KV, Blüher M, Kosacka J, Nowicki MInflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)-New Aspects.Int J Mol Sci.(2021-Oct-07)
  27. ^Vincent AM, Callaghan BC, Smith AL, Feldman ELDiabetic neuropathy: cellular mechanisms as therapeutic targets.Nat Rev Neurol.(2011-Sep-13)
Examine Database References
  1. Diabetic Neuropathy Symptoms - K K Kiew, W B Wan Mohamad, A Ridzuan, M MafauzyEffects of sulbutiamine on diabetic polyneuropathy: an open randomised controlled study in type 2 diabeticsMalays J Med Sci.(2002 Jan)
  2. Diabetic Neuropathy Symptoms - Foster TSEfficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathyDiabetes Educ.(2007 Jan-Feb)
  3. Diabetic Neuropathy Symptoms - Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schütte K, Dyck PJEfficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trialDiabetes Care.(2011 Sep)
  4. Diabetic Neuropathy Symptoms - Dinesh Selvarajah, Rajiv Gandhi, Celia J Emery, Solomon TesfayeRandomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factorDiabetes Care.(2010 Jan)
  5. Diabetic Neuropathy Symptoms - Mark S Wallace, Thomas D Marcotte, Anya Umlauf, Ben Gouaux, Joseph H AtkinsonEfficacy of Inhaled Cannabis on Painful Diabetic NeuropathyJ Pain.(2015 Jul)
  6. Diabetic Neuropathy Symptoms - Sheyu Li, Xiang Chen, Qianrui Li, Juan Du, Zhimin Liu, Yongde Peng, Mian Xu, Qifu Li, Minxiang Lei, Changjiang Wang, Shaoxiong Zheng, Xiaojuan Zhang, Hongling Yu, Jinyu Shi, Shibing Tao, Ping Feng, Haoming TianEffects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trialJ Diabetes Investig.(2016 Sep)
  7. Blood glucose - Li XS, Zheng WY, Lou SX, Lu XW, Ye SHEffect of Ginkgo leaf extract on vascular endothelial function in patients with early stage diabetic nephropathyChin J Integr Med.(2009 Feb)
  8. Advanced Glycation End Products - Alkhalaf A, Kleefstra N, Groenier KH, Bilo HJ, Gans RO, Heeringa P, Scheijen JL, Schalkwijk CG, Navis GJ, Bakker SJEffect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathyPLoS One.(2012)