Medscape is available in 5 Language Editions – Choose your Edition here.


Diabetic Neuropathy Workup

  • Author: Dianna Quan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
Updated: Jul 06, 2016

Approach Considerations

Fasting plasma glucose and hemoglobin A1c are important laboratory screening tests for diabetic neuropathy.

Imaging studies rarely help the physician diagnose or manage diabetic neuropathy. However, in the appropriate clinical setting, MRI of the cervical, thoracic, and/or lumbar regions may help exclude another cause for symptoms mimicking diabetic neuropathy.

Multiple consensus panels recommend the inclusion of electrophysiologic testing in the evaluation of diabetic neuropathy. An appropriate array of electrodiagnostic tests includes both nerve conduction testing and needle EMG of the most distal muscles usually affected.

In a systematic review of 5 studies of noninvasive screening tools for detecting peripheral neuropathies in pediatric patients with type 1 diabetes, Hirschfeld and colleagues found that the diagnostic utility of the Rydel-Seiffer tuning fork and 10-g Semmes-Weinstein monofilament was low, while that of biothesiometry and a finer (1-g) monofilament was acceptable. Sensitivities and specificities of these screening tools were as follows:[58, 59]

  • Tuning fork: 87-99% (sensitivity); 1-19% (specificity)
  • Coarse monofilament: 16% (sensitivity); 64% (specificity)
  • Fine monofilament: 73% (sensitivity); 87% (specificity)
  • Biothesiometer: 61-80% (sensitivity); 64-76% (specificity)

Hemoglobin A1c and Fasting Plasma Glucose

Hemoglobin A1c and fasting plasma glucose are important laboratory screening tests for diabetic neuropathy. Hemoglobin A1c measurement is useful to assess the adequacy of recent diabetes control; levels are likely to be elevated in patients with diabetic neuropathies. In some cases, especially with asymmetrical syndromes, the severity of the elevation does not always correlate with the severity of the nerve disease.

A 3-hour glucose tolerance test may be more sensitive in borderline cases. A urinalysis is also helpful to screen for nephropathy and proteinuria.


Basic Laboratory Screening Tests

Testing is tailored depending on the clinical presentation. Examples of tests suggested as basic screening tools to exclude common causes of neuropathy other than diabetes include the following:

  • Complete blood cell count
  • Complete metabolic panel (electrolytes and liver function panel)
  • Vitamin B-12 and folate levels
  • Thyroid function tests
  • Erythrocyte sedimentation rate
  • C-reactive protein
  • Serum protein electrophoresis with immunofixation electrophoresis
  • Antinuclear antibody
  • Anti-SSA and SSB antibodies
  • Rheumatoid factor
  • Paraneoplastic antibodies
  • Rapid plasma reagin
  • Genetic screens
  • Hematology screen to check for anemia
  • Sequential multiple analysis-7 (SMA7) to check renal function and electrolyte imbalances/complete metabolic panel (CMP)

For more information, see Type 2 Diabetes and TCF7L2.


Electromyography and Nerve Conduction Studies

Nerve conduction studies (NCS) and electromyography (EMG) can document the characteristics of the neuropathy (eg, axonal, demyelinating) and the localization (eg, mononeuropathy versus radiculopathy or distal neuropathy) and, possibly, the severity and even prognosis for morbidity. Multiple consensus panels recommend the inclusion of electrophysiologic testing in the evaluation of diabetic neuropathy. These same panels recommend the use of nerve conduction velocity (NCV)/EMG procedures in clinical research studies. An appropriate array of electrodiagnostic tests includes both nerve conduction testing and needle EMG of the most distal muscles usually affected.

Conventional nerve conduction velocity studies

Conventional NCV testing includes measurement of the speed of both motor and sensory conduction. The amplitude of the distal response is also measured. The proximal component of conduction can be investigated with H-reflex (S1 root) or F-wave (motor pathways only) response.

Needle electromyography

Needle EMG is performed in the distal muscles in cases of generalized neuropathy and entrapment, in the proximal limb muscles in amyotrophy, and in the paraspinal and limb muscles in suspected radiculopathy. The examiner searches for abnormal spontaneous potentials, voluntary motor unit recruitment, and motor unit configuration. In weak patients, the recruitment characteristics can often help distinguish a neuropathic from a myopathic process.

Nerve conduction study findings

Findings on nerve conduction studies depend on the pattern of nerve damage. Patients with distal symmetrical sensorimotor polyneuropathy from predominant axonal loss have reduced or absent sensory nerve action potentials, especially in the legs. With progression of neuropathy, compound motor action potential amplitudes may also be reduced and abnormalities may be observed in the hands. These changes reflect length-dependent degeneration of large-diameter myelinated nerve fibers.

Conduction velocities are generally within the normal range or only mildly slowed in distal symmetrical polyneuropathy. If conduction velocities are less than 70% of the lower limit of normal, or if conduction block is present, the patient may have superimposed peripheral nerve demyelination in addition to the more typical axonal loss seen in distal symmetrical polyneuropathy. Generalized demyelinating changes on nerve conduction studies should prompt further evaluation for CIDP. Focal slowing of conduction velocity at common sites of entrapment may indicate one of the mononeuropathy syndromes discussed above.

In patients with diabetes, nerve conduction study abnormalities may be found even in the absence of clinical symptoms of polyneuropathy.

Electromyographic sampling of distal lower extremity muscles may reveal acute and ongoing denervation in the form of positive sharp waves and fibrillation potentials (spontaneous discharges). Reinnervation changes such as large-amplitude, long-duration, and polyphasic motor unit potentials reflect chronicity. Abnormalities in paraspinal muscles (eg, spontaneous discharges) usually reflect disease in spinal nerve roots.

Some studies have proposed that the severity of electrophysiologic abnormalities not only correlates with symptoms but also predicts the level of morbidity related to DM. Most authors suggest the NCV results to be stable or worsening over time; however, in 1998, Tkac found that the NCV levels could improve with glycemic control.[60]


Electrophysiologic Studies

Electrophysiologic studies are the most sensitive, reliable, and reproducible measures of nerve function.[61] Electrophysiologic findings usually correlate with morphologic changes on nerve biopsy. Common early findings are abnormal nerve conduction studies or reduced variability of heart rate with deep breathing or Valsalva maneuver. Although electrodiagnostic studies can characterize and quantitate nerve dysfunction, they cannot distinguish diabetic neuropathy from neuropathy of other causes.

Composite scores, combining clinical, quantitative sensory,[34] and electrophysiologic measures, are often used in natural history and efficacy studies. Examples include the Neuropathy Impairment Score in the Lower Limbs + 7 and the Michigan Diabetic Neuropathy score.[42, 62]


MRI and CT

Plexus MRI may be helpful to exclude other problems (eg, tumor) in patients with radiculoplexus neuropathy syndromes. For patients who cannot have MRI, CT myelography is an alternative to exclude compressive lesions and other pathology in the spinal canal. In cranial nerve palsies, brain imaging, usually with MRI, is helpful to exclude intracranial aneurysms, compressive lesions, and infarcts.


Nuclear Imaging

Scintigraphic techniques are used to detect and quantify cardiac autonomic neuropathy (for research purposes). Techniques include radiolabeled analogs of norepinephrine, 123I-metaiodobenzylguanidine (MIBG), and 11C-hydroxyephedrine. Adrenergic nerve terminals of the heart actively take up these compounds. Combining this technique with single-photon emission computed tomography (SPECT) scanning allows detection of decreased innervation of the heart.


Doppler Imaging

Laser Doppler can be used to measure skin perfusion. In this test, skin blood flow is measured by continuous laser Doppler assessment in response to several stimuli.



Microdialysis has been used to study nitric oxide release, which participates in vasodilation of the microvasculature. In this test, probes are inserted into the dermis (with an ISO-NO Mark II oxide meter, a microsensor that measures nitric oxide release from single cells).



Electrocardiography may reveal prolongation of the QT interval. This is secondary to imbalance between right and left heart sympathetic innervation. This abnormality is thought to increase risk of arrhythmias. A screening ECG is advisable for patients with longstanding DM.


Nerve and Skin Biopsy

A nerve biopsy can be obtained, typically of the sural nerve, to confirm and help diagnose the neuropathic stage (ie, mild, moderate, severe). However, this is an invasive procedure and carries the risk of producing chronic pain, numbness, and cold insensitivity in the distribution of the sural nerve. Thus, with NCV/EMG and QST available, the sural nerve biopsy is rarely needed for diagnostic purposes any longer.

A skin biopsy can be obtained for research purposes only. Immunohistochemistry is used to quantify the cutaneous nerves to provide a morphologic assessment of diabetic neuropathies. This tool is new for clinical research, and it is used as an endpoint in diabetic neuropathy. The procedure requires only a 3-cm skin biopsy and enables a direct study of small nerve fibers (ie, C-fibers) that produce pain and temperature sensation.

Biopsy rarely is recommended for clinical purposes. Reasons for this move away from biopsies in clinical trials include the invasive nature of the procedure with its attendant risks, discomfort to the patient, cost, problems with reproducibility due to sampling error, and availability of other methods to obtain similar information. This study is performed primarily when the etiology of the neuropathy is in question or in research settings. Several studies have looked at biopsies, mainly of the sural nerve in humans. These studies were performed in advanced neuropathy; vessels were found to be thickened, and nerves were found to have undergone severe damage. Indications of nerve regrowth were small and weak.


Future Approaches

The following additional diagnostic approaches for diabetic neuropathy are currently in use or under intense study. Details of these techniques are beyond the scope of this review.

  • Skin punch biopsy/intraepidermal nerve fiber density testing [63] and immunohistochemical staining of peripheral nerves
  • Quantitative sensory testing
  • Imaging using MRI and ultrasonography
Contributor Information and Disclosures

Dianna Quan, MD Professor of Neurology, Director of Electromyography Laboratory, University of Colorado School of Medicine

Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association

Disclosure: Nothing to disclose.


Helen C Lin, MD Assistant Professor of Neurology, Medical College of Wisconsin

Helen C Lin, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.


Neil A Busis, MD Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside

Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Milind J Kothari, DO Professor and Vice-Chair, Department of Neurology, Pennsylvania State University College of Medicine; Consulting Staff, Department of Neurology, Penn State Milton S Hershey Medical Center

Milind J Kothari, DO is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Boulton AJ, Malik RA. Diabetic neuropathy. Med Clin North Am. 1998 Jul. 82(4):909-29. [Medline].

  2. Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neuropathy. F1000Res. 2016. 5:[Medline]. [Full Text].

  3. Bromberg MB. Peripheral neurotoxic disorders. Neurol Clin. 2000 Aug. 18(3):681-94. [Medline].

  4. Goetz CG, Pappert EJ. Textbook of Clinical Neurology. Philadelphia: WB Saunders Co; 1999.

  5. Pourmand R. Diabetic neuropathy. Neurol Clin. 1997 Aug. 15(3):569-76. [Medline].

  6. Sugimoto K, Murakawa Y, Sima AA. Diabetic neuropathy--a continuing enigma. Diabetes Metab Res Rev. 2000 Nov-Dec. 16(6):408-33. [Medline].

  7. Vinik AI, Park TS, Stansberry KB, Pittenger GL. Diabetic neuropathies. Diabetologia. 2000 Aug. 43(8):957-73. [Medline].

  8. Wilson JD. Williams Textbook of Endocrinology. 9th ed. Philadelphia: WB Saunders Co; 1998.

  9. Zochodne DW. Diabetic polyneuropathy: an update. Curr Opin Neurol. 2008 Oct. 21(5):527-33. [Medline].

  10. Calcutt NA, Dunn JS. Pain: Nociceptive and Neuropathic Mechanisms. Anesthesiology Clinics of North America.; 1997.

  11. Malik RA. Pathology and pathogenesis of diabetic neuropathy. Diabetes Reviews. 1999. 7:253-60.

  12. Shigeta H, Yamaguchi M, Nakano K, Obayashi H, Takemura R, Fukui M. Serum autoantibodies against sulfatide and phospholipid in NIDDM patients with diabetic neuropathy. Diabetes Care. 1997 Dec. 20(12):1896-9. [Medline].

  13. Tavakkoly-Bazzaz J, Amoli MM, Pravica V, Chandrasecaran R, Boulton AJ, Larijani B. VEGF gene polymorphism association with diabetic neuropathy. Mol Biol Rep. 2010 Mar 30. [Medline].

  14. Carrington AL, Litchfield JE. The aldose reductase pathway and nonenzymatic glycation in the pathogenesis of diabetic neuropathy: a critical review for the end of the 20th century. Diabetes Reviews. 1999. 7:275-99.

  15. Greene DA, Arezzo JC, Brown MB. Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Zenarestat Study Group. Neurology. 1999 Aug 11. 53(3):580-91. [Medline].

  16. Ryle C, Donaghy M. Non-enzymatic glycation of peripheral nerve proteins in human diabetics. J Neurol Sci. 1995 Mar. 129(1):62-8. [Medline].

  17. Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov. 29(11):2365-70. [Medline].

  18. Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: The oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord. 2008 Dec. 9(4):301-14. [Medline].

  19. Ziegler D, Reljanovic M, Mehnert H, Gries FA. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrinol Diabetes. 1999. 107(7):421-30. [Medline].

  20. Apfel SC, Kessler JA, Adornato BT, et al. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology. 1998 Sep. 51(3):695-702. [Medline].

  21. Krendel DA, Zacharias A, Younger DS. Autoimmune diabetic neuropathy. Neurol Clin. 1997 Nov. 15(4):959-71. [Medline].

  22. Dorsey RR, Eberhardt MS, Gregg EW, Geiss LS. Control of risk factors among people with diagnosed diabetes, by lower extremity disease status. Prev Chronic Dis. 2009 Oct. 6(4):A114. [Medline]. [Full Text].

  23. Diabetes control and complications trial research group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30. 329(14):977-86. [Medline].

  24. Harati Y. Diabetes and the nervous system. Endocrinol Metab Clin North Am. 1996 Jun. 25(2):325-59. [Medline].

  25. Rutkove SB. A 52-year-old woman with disabling peripheral neuropathy: review of diabetic polyneuropathy. JAMA. 2009 Oct 7. 302(13):1451-8. [Medline].

  26. Finucane TE. Diabetic polyneuropathy and glucose control. JAMA. 2010 Feb 3. 303(5):420; author reply 420-1. [Medline].

  27. Boulton AJ, Malik RA. Neuropathy of impaired glucose tolerance and its measurement. Diabetes Care. 2010 Jan. 33(1):207-9. [Medline]. [Full Text].

  28. Altaf QA, Ali A, Piya MK, Raymond NT, Tahrani AA. The relationship between obstructive sleep apnea and intra-epidermal nerve fiber density, PARP activation and foot ulceration in patients with type 2 diabetes. J Diabetes Complications. 2016 Jun 2. [Medline].

  29. Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr. 43(4):817-24. [Medline].

  30. Perkins BA, Olaleye D, Bril V. Carpal tunnel syndrome in patients with diabetic polyneuropathy. Diabetes Care. 2002 Mar. 25(3):565-9. [Medline].

  31. Shaw JE, Zimmet PZ. The epidemiology of diabetic neuropathy. Diabetes Reviews. 1999. 7:245-52.

  32. Singh R, Gamble G, Cundy T. Lifetime risk of symptomatic carpal tunnel syndrome in Type 1 diabetes. Diabet Med. 2005 May. 22(5):625-30. [Medline].

  33. Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000 Feb. 47(2):123-8. [Medline].

  34. Dyck PJ, O'Brien PC. Quantitative sensation testing in epidemiological and therapeutic studies of peripheral neuropathy. Muscle Nerve. 1999 Jun. 22(6):659-62. [Medline].

  35. Pirart J. Diabetes mellitus and its degenerative complication: a prospective study of 4,400 patient observed between 1947 and 1973. Diabetes Care. 1978. 1:168-188.

  36. Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993 Feb. 36(2):150-4. [Medline].

  37. Aaberg ML, Burch DM, Hud ZR, Zacharias MP. Gender differences in the onset of diabetic neuropathy. J Diabetes Complications. 2008 Mar-Apr. 22(2):83-7. [Medline].

  38. D'Amato C, Morganti R, Greco C, et al. Diabetic peripheral neuropathic pain is a stronger predictor of depression than other diabetic complications and comorbidities. Diab Vasc Dis Res. 2016 Jun 22. [Medline].

  39. Tesfaye S, Watt J, Benbow SJ, Pang KA, Miles J, MacFarlane IA. Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet. 1996 Dec 21-28. 348(9043):1698-701. [Medline].

  40. Johnson DA, Vinik AI. Gastrointestinal Disturbances. Therapy for Diabetes Mellitus. American Diabetes Association; 1998.

  41. Ziegler D. Cardiovascular autonomic neuropathy: clinical manifestations and measurement. Diabetes Reviews. 1999. 7:342-57.

  42. Meijer JW, van Sonderen E, Blaauwwiekel EE, et al. Diabetic neuropathy examination: a hierarchical scoring system to diagnose distal polyneuropathy in diabetes. Diabetes Care. 2000 Jun. 23(6):750-3. [Medline].

  43. Hokkam EN. Assessment of risk factors in diabetic foot ulceration and their impact on the outcome of the disease. Prim Care Diabetes. 2009 Nov. 3(4):219-24. [Medline].

  44. Coppini DV, Wellmer A, Weng C, Young PJ, Anand P, Sönksen PH. The natural history of diabetic peripheral neuropathy determined by a 12 year prospective study using vibration perception thresholds. J Clin Neurosci. 2001 Nov. 8(6):520-4. [Medline].

  45. Perkins BA, Olaleye D, Zinman B, Bril V. Simple screening tests for peripheral neuropathy in the diabetes clinic. Diabetes Care. 2001 Feb. 24(2):250-6. [Medline].

  46. Dyck PJ, Turner DW, Davies JL, O'Brien PC, Dyck PJ, Rask CA. Electronic case-report forms of symptoms and impairments of peripheral neuropathy. Can J Neurol Sci. 2002 Aug. 29(3):258-66. [Medline].

  47. Biaggioni I. Postural hypotension. Therapy for Diabetes Mellitus. American Diabetes Association; 1998. 423-30.

  48. Ayad H. Diabetic neuropathy: classification, clinical manifestations, diagnosis and management. Baba S et al, eds. Diabetes Mellitus in Asia. Amsterdam: Excerpta Medica; 1977. 222-4.

  49. Thomas PK. Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes. 1997 Sep. 46 Suppl 2:S54-7. [Medline].

  50. All About Diabetes. Date Accessed: October 30, 2008. American Diabetes Association. [Full Text].

  51. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: A report of the World Health Organization and International Diabetes Federation. Geneva, Switzerland: WHO Press; 2006.

  52. Abbott CA, Vileikyte L, Williamson S, et al. Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration. Diabetes Care. 1998 Jul. 21(7):1071-5. [Medline].

  53. Llewelyn JG, Tomlinson DR, Thomas PK. Dyck PJ and Thomas PK. Diabetic Neuropathies in Peripheral Neuropathy. Philadelphia: Elsevier Saunders; 2005. 1951-91.

  54. Lozeron P, Nahum L, Lacroix C, Ropert A, Guglielmi JM, Said G. Symptomatic diabetic and non-diabetic neuropathies in a series of 100 diabetic patients. J Neurol. 2002 May. 249(5):569-75. [Medline].

  55. Waldman SD. Diabetic neuropathy: diagnosis and treatment for the pain management specialist. Curr Rev Pain. 2000. 4(5):383-7. [Medline].

  56. Davidson MB. Diabetes Mellitus: Diagnosis and Treatment. 4th Ed. 1998. 297-307.

  57. Vinik AI. New Methods to Assess Diabetic Neuropathy for Clinical Research.60th Scientific Sessions of the American Diabetes Association. American Diabetes Association; 2000.

  58. Busko M. Common Tests May Miss Pediatric Diabetic Neuropathy. Medscape Medical News. Apr 11 2014. [Full Text].

  59. Hirschfeld G, von Glischinski M, Blankenburg M, et al. Screening for peripheral neuropathies in children with diabetes: a systematic review. Pediatrics. 2014 Apr 7. [Medline].

  60. Tkac I, Bril V. Glycemic control is related to the electrophysiologic severity of diabetic peripheral sensorimotor polyneuropathy. Diabetes Care. 1998 Oct. 21(10):1749-52. [Medline].

  61. Bril V. Electrophysiologic testing. Gries FA, Cameron NE, Low PA, Ziegler D. Textbook of Diabetic Neuropathy. Stuttgart, Germany: Thieme Medical Publishers; 2003. 177-84.

  62. Huang CC, Chen TW, Weng MC, Lee CL, Tseng HC, Huang MH. Effect of glycemic control on electrophysiologic changes of diabetic neuropathy in type 2 diabetic patients. Kaohsiung J Med Sci. 2005 Jan. 21(1):15-21. [Medline].

  63. Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006 Jun. 29(6):1294-9. [Medline].

  64. Apfel SC. Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med. 1999 Aug 30. 107(2B):34S-42S. [Medline].

  65. Apfel SC. Diabetic Polyneuropathy. Diabetes and Endocrinology Clinical Management. 1999.

  66. Argoff CE, Backonja MM, Belgrade MJ, Bennett GJ, Clark MR, Cole BE, et al. Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain. Mayo Clin Proc. 2006 Apr. 81(4 Suppl):S12-25. [Medline].

  67. Boulton A. Current and Emerging Treatments for Diabetic Neuropathies. Diabetes Reviews. 7:379-86.

  68. Slovenkai MP. Foot problems in diabetes. Med Clin North Am. 1998 Jul. 82(4):949-71. [Medline].

  69. O'Brien SP, Schwedler M, Kerstein MD. Peripheral neuropathies in diabetes. Surg Clin North Am. 1998 Jun. 78(3):393-408. [Medline].

  70. Skyler JS. Diabetic complications. The importance of glucose control. Endocrinol Metab Clin North Am. 1996 Jun. 25(2):243-54. [Medline].

  71. Martin CL, Albers J, Herman WH, et al. Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care. 2006 Feb. 29(2):340-4. [Medline].

  72. Sumner CJ, Sheth S, Griffin JW, et al. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology. 2003 Jan 14. 60(1):108-11. [Medline].

  73. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012 Jun 13. 6:CD007543. [Medline].

  74. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2011 Mar 16. CD007938. [Medline].

  75. Ziegler D. Treatment of diabetic neuropathy and neuropathic pain: how far have we come?. Diabetes Care. 2008 Feb. 31 Suppl 2:S255-61. [Medline].

  76. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy or chronic pain. Cochrane Database Syst Rev. 2009. (4):CD007115. [Medline].

  77. Chou R, Carson S, Chan BK. Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials. J Gen Intern Med. 2009 Feb. 24(2):178-88. [Medline].

  78. Hayee MA, Mohammad QD, Haque A. Diabetic neuropathy and zinc therapy. Bangladesh Med Res Counc Bull. 2005 Aug. 31(2):62-7. [Medline].

  79. Kawai T, Takei I, Tokui M, Funae O, Miyamoto K, Tabata M, et al. Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of N(varepsilon)-carboxymethyl lysine. J Diabetes Complications. 2009 Aug 26. [Medline].

  80. Schemmel KE, Padiyara RS, D'Souza JJ. Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review. J Diabetes Complications. 2009 Sep 10. [Medline].

  81. Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, et al. Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial. Diabetes Care. 2006 Jul. 29(7):1538-44. [Medline].

  82. Ando H, Takamura T, Nagai Y, Kaneko S,. Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy. J Diabetes Complications. 2006 Nov-Dec. 20(6):367-70. [Medline].

  83. Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, et al. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005 Jan 27. 352(4):341-50. [Medline].

  84. Daousi C, Benbow SJ, MacFarlane IA. Electrical spinal cord stimulation in the long-term treatment of chronic painful diabetic neuropathy. Diabet Med. 2005 Apr. 22(4):393-8. [Medline].

  85. Ahn AC, Bennani T, Freeman R, Hamdy O, Kaptchuk TJ. Two styles of acupuncture for treating painful diabetic neuropathy--a pilot randomised control trial. Acupunct Med. 2007 Jun. 25(1-2):11-7. [Medline].

  86. Miller RD. Anesthesia. 5th ed. New York: Churchill Livingstone; 2000.

  87. Ferreira MC, Carvalho VF, Kamamoto F, Tuma P Jr, Paggiaro AO. Negative pressure therapy (vacuum) for wound bed preparation among diabetic patients: case series. Sao Paulo Med J. 2009. 127(3):166-70. [Medline].

  88. Crouch J. Charcot's joint and bilateral foot neuropathy. Adv Nurse Pract. 2005 Mar. 13(3):18. [Medline].

  89. Pfeiffer MA, Schumer M. Painful or insensitive lower extremity. Therapy for Diabetes Mellitus. American Diabetes Association; 1998.

  90. Somers DL, Somers MF. Treatment of neuropathic pain in a patient with diabetic neuropathy using transcutaneous electrical nerve stimulation applied to the skin of the lumbar region. Phys Ther. 1999 Aug. 79(8):767-75. [Medline].

  91. [Guideline] Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. Prepublished online April 11, 2011. [Full Text].

  92. Tavakoli M, Kallinikos P, Iqbal A, et al. Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabet Med. 2011 Oct. 28(10):1261-7. [Medline]. [Full Text].

  93. Possidente CJ, Tandan R. A survey of treatment practices in diabetic peripheral neuropathy. Prim Care Diabetes. 2009 Nov. 3(4):253-7. [Medline].

  94. Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998 Dec 2. 280(21):1831-6. [Medline].

  95. Bennett GJ, Dworkin RH, Nicholson B. Anticonvulsant Therapy in the Treatment of Neuropathic Pain. Neurology Treatment Update. 2000.

  96. Bomholt SF, Mikkelsen JD, Blackburn-Munro G. Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain. Neuropharmacology. 2005 Feb. 48(2):252-63. [Medline].

  97. Ziegler D, Movsesyan L, Mankovsky B, Gurieva I, Abylaiuly Z, Strokov I. Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients. Diabetes Care. 2009 Aug. 32(8):1479-84. [Medline]. [Full Text].

  98. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004 Dec 14. 63(11):2104-10. [Medline].

  99. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011 Apr 11. [Medline].

  100. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev. 2011 Jan 19. CD005451. [Medline].

  101. FDA Requires Boxed Warning and Risk Mitigation Strategy for Metoclopramide-Containing Drugs. U.S. Food and Drug Administration. Available at Accessed: May 16, 2000.

  102. Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005 Apr. 28(4):956-62. [Medline].

  103. Brooks M. Tear film dysfunction a marker of diabetic neuropathy. Medscape Medical News. November 7, 2013. Available at Accessed: November 12, 2013.

Table. Subdivisions of Sensory Neurons
Fiber Type Size Modality Myelination
A-alpha (I) 13-20 micrometers Limb proprioception Yes
A-beta (II) 6-12 micrometers Limb proprioception, vibration, pressure Yes
A-delta (III) 1-5 micrometers Mechanical sharp pain Yes
C (IV) 0.2-1.5 micrometers Thermal pain, mechanical burning pain No
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.