Close
New

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

 

Diabetic Neuropathy Clinical Presentation

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

History

In type 1 diabetes mellitus, distal polyneuropathy typically becomes symptomatic after many years of chronic prolonged hyperglycemia. Conversely, patients with type 2 diabetes mellitus may present with distal polyneuropathy after only a few years of known poor glycemic control; sometimes, these patients already have neuropathy at the time of diagnosis.

Since diabetic neuropathy can manifest as a wide variety of sensory, motor, and autonomic symptoms, a structured list of symptoms can be used to help screen all diabetic patients for possible neuropathy.

Sensory symptoms

Sensory neuropathy usually is insidious in onset and shows a stocking-and-glove distribution in the distal extremities. Sensory symptoms may be negative or positive, diffuse or focal. Negative sensory symptoms include feelings of numbness or deadness, which patients may describe as being akin to wearing gloves or socks. Loss of balance, especially with the eyes closed, and painless injuries due to loss of sensation are common. Positive symptoms may be described as burning, prickling pain, tingling, electric shock–like feelings, aching, tightness, or hypersensitivity to touch.

Motor symptoms

Motor problems may include distal, proximal, or more focal weakness. In the upper extremities, distal motor symptoms may include impaired fine hand coordination and difficulty with tasks such as opening jars or turning keys. Foot slapping and toe scuffing or frequent tripping may be early symptoms of foot weakness. Symptoms of proximal limb weakness include difficulty climbing up and down stairs, difficulty getting up from a seated or supine position, falls due to the knees giving way, and difficulty raising the arms above the shoulders.

In the most common presentation of diabetic neuropathy with symmetrical sensorimotor symptoms, minor weakness of the toes and feet may be seen; severe weakness is uncommon and should prompt investigation into other causes, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or vasculitis. More severe weakness may be observed in asymmetrical diabetic neuropathy syndromes. Motor neuropathy may occur along with sensory neuropathy (sensorimotor neuropathy).

Autonomic symptoms

Autonomic neuropathy may involve the cardiovascular, gastrointestinal, and genitourinary systems and the sweat glands. Patients with generalized autonomic neuropathies may report ataxia, gait instability, or near syncope/syncope. In addition, autonomic neuropathies have further symptoms that relate to the anatomic site of nerve damage—gastrointestinal, cardiovascular, bladder, or sudomotor.

Gastrointestinal autonomic neuropathy may produce the following symptoms[40] :

  • Dysphagia
  • Abdominal pain
  • Nausea/vomiting
  • Malabsorption
  • Fecal incontinence
  • Diarrhea
  • Constipation

Cardiovascular autonomic neuropathy may produce the following symptoms[41] :

  • Persistent sinus tachycardia
  • Orthostatic hypotension
  • Sinus arrhythmia
  • Decreased heart variability in response to deep breathing
  • Near syncope upon changing positions from recumbent to standing

Bladder neuropathy (which must be differentiated from prostate or spine disorders) may produce the following symptoms:

  • Poor urinary stream
  • Feeling of incomplete bladder emptying
  • Straining to void

Sudomotor neuropathy may produce the following symptoms:

  • Heat intolerance
  • Heavy sweating of head, neck, and trunk with anhidrosis of lower trunk and extremities
  • Gustatory sweating
Next

Physical Examination

Physical examination of patients with suspected distal sensory, motor, or focal (ie, entrapment or noncompressive) neuropathic symptoms should include assessments for both peripheral and autonomic neuropathy.[42]

Peripheral neuropathy testing

Testing for peripheral neuropathy begins with assessment of gross light touch and pinprick sensation. The first clinical sign that usually develops in diabetic symmetrical sensorimotor polyneuropathy is decrease or loss of vibratory and pinprick sensation over the toes. As disease progresses, the level of decreased sensation may move upward into the legs and then from the hands into the arms, a pattern often referred to as "stocking and glove" sensory loss. Very severely affected patients may lose sensation in a "shield" distribution on the chest.

Vibratory sense in the feet is tested with a 128-Hz tuning fork placed at the base of the great toenail. Test protective sensation with 5.07 Semmes-Weinstein monofilament, briefly applying the tip perpendicular to the plantar surface of the foot, using sufficient force (10 g) to buckle the monofilament. Inability to perceive the tuning fork or the monofilament identifies patients who are at increased risk (ie, 60% in the next 3 years) of developing a foot ulcer.[43] The 2 tests should be performed at least every year.[44]

Test deep tendon reflexes. With neuropathy, these are commonly hypoactive or absent. Perform strength testing and examine for distal intrinsic extremity muscle atrophy, since weakness of small foot muscles may develop. Check dorsal pedal and posterior tibial pulses.

Examine the skin for dryness, tinea pedis, cracks, onychomycoses, acute erythema and tenderness, and fluctuance under calluses.

Perform Tinel testing. Paresthesias or pain suggests median nerve injury.

Perform cranial nerve testing. Have the patient walk on the heels and toes; heel-toe walking tests not only distal lower-extremity strength but balance, as well.

Perkins et al recommended conducting annual screening for diabetic neuropathy using superficial pain sensation testing, monofilament testing, or vibration testing by the on-off method. These researchers also validated a scoring system to document and monitor neuropathy in the clinic.[45] Dyck et al described case report forms for recording symptoms and signs of neuropathy that might be useful in longitudinal follow-up of individual patients.[46]

Autonomic neuropathy testing

Testing for autonomic neuropathies is performed objectively in a specialized autonomic laboratory, evaluating cardiovagal, adrenergic, and sudomotor function. However, the clinician may first perform bedside screening to assess if further, more specialized testing is necessary.

Blood pressure and heart rate measurements with the patient supine and upright are compared. Blood pressure measurements in patients with autonomic neuropathy may show orthostatic hypotension with reduced compensatory tachycardia. Testing for orthostatic hypotension is particularly important in patients with longstanding diabetes mellitus.[47]

The sinus arrhythmia (SA) ratio is measured with the patient breathing 6 times per minute while the heart rate is monitored with a continuous ECG strip. The longest R-R interval during expiration and the shortest R-R interval during inspiration are measured, and the average of the 6 breaths is taken. The SA ratio is R-R expiration/R-R inspiration. The normal ratio is 1:2.

Previous
Next

Classification of Diabetic Neuropathy

Diabetic neuropathies are heterogeneous in type; thus, several classifications of diabetic neuropathy have been created and recognized.[48, 1, 42] Two classification systems will be presented here: the Thomas system and symmetrical-versus-asymmetrical neuropathies.

Thomas system

A classification system by Thomas[49] combines anatomy and pathophysiology. It is presented below with a few modifications:

  • Hyperglycemic neuropathy (acute)
  • Generalized symmetrical polyneuropathies
  • Sensory neuropathy
  • Sensorimotor neuropathy (chronic, symmetric)
  • Autonomic neuropathy (cardiovascular, gastrointestinal, genitourinary, sudomotor)
  • Focal and multifocal neuropathies: this category includes cranial neuropathy, proximal motor neuropathy (amyotrophy), thoracic or lumbar radiculopathies, and focal limb neuropathies (entrapment neuropathies)
  • Superimposed chronic inflammatory demyelinating polyneuropathy (CIDP)

Symmetrical versus asymmetrical neuropathies

Another generally accepted classification of diabetic neuropathies divides them broadly into symmetrical and asymmetrical neuropathies.

Symmetrical polyneuropathies involve multiple nerves diffusely and symmetrically. Distal symmetrical sensorimotor polyneuropathy is the most common manifestation of diabetic neuropathy. The syndrome has been defined in many ways, but 3 key criteria are commonly accepted:

  • The patient must have diabetes mellitus by one of the widely accepted definitions such as those outlined by the American Diabetes Association or World Health Organization [50, 51]
  • The severity of polyneuropathy should be commensurate with the duration and severity of the diabetes
  • Other causes of sensorimotor polyneuropathy must be excluded

Distal symmetrical sensorimotor polyneuropathy affects sensory, motor, and autonomic functions in varying degrees, with sensory abnormalities predominating. Chronic symmetrical symptoms affect peripheral nerves in a length-dependent pattern, with the longest nerves affected first. Patients commonly present with painful paresthesias and numbness, which begin in the toes and ascend proximally in a stocking-like distribution over months and years.

When sensory symptoms ascend above the knees, similar symptoms develop in the hands, progressing proximally in a glove-like distribution. At a very late stage, the anterior aspect of the trunk and vertex of the head may be affected. The loss of sensation in the feet predisposes to development of foot ulcers and gangrene.[52] In addition, mild weakness of foot muscles and decreased ankle and knee reflexes occur commonly. With impaired proprioception and vibratory perception, gait may be affected (sensory ataxia).

Small-fiber neuropathy is a distal symmetrical neuropathy involving predominantly small-diameter sensory fibers (A delta and C fibers). It manifests as painful paresthesias that patients perceive as burning, stabbing, crushing, aching, or cramplike, with increased severity at night. There is loss of pain and temperature sensation with relative sparing of distal reflexes and proprioception.

Although some degree of autonomic involvement is present in most patients with distal symmetrical diabetic polyneuropathy, patients may not notice autonomic problems, and pure autonomic diabetic neuropathy is rare. Manifestations of autonomic neuropathy may include orthostatic hypotension, resting tachycardia, loss of normal sinus arrhythmia ratio, anhidrosis, bowel or bladder dysfunction, and small pupils sluggishly reactive to light.

In diabetic neuropathic cachexia, the patient experiences a precipitous and profound weight loss followed by severe and unremitting cutaneous pain, small-fiber neuropathy, and autonomic dysfunction. This condition occurs more often in older men; impotence is common. Muscle weakness is uncommon. The condition usually improves with prolonged glycemic control; however, symptoms are often refractory to other pharmacologic treatment. Limited anecdotal improvement is reported with nonpharmacologic treatments such as sympathectomy, spinal cord blockade, and electrical spinal cord stimulation. Recovery may be incomplete and prolonged over many months

Asymmetrical neuropathies include single or multiple cranial or somatic mononeuropathies. Syndromes include the following:

  • Median neuropathy of the wrist (carpal tunnel syndrome)
  • Other single or multiple limb mononeuropathies
  • Thoracic radiculoneuropathy
  • Lumbosacral radiculoplexus neuropathy
  • Cervical radiculoplexus neuropathy

These syndromes are distinguished from typical distal diabetic polyneuropathy by the following characteristics:

  • They often have a monophasic course
  • Some are associated with inflammatory angiitis and ischemia (eg, lumbosacral radiculoplexus neuropathy) and may appear acutely or subacutely
  • They have a weaker association with total hyperglycemic exposure than symmetrical polyneuropathies

Cranial mononeuropathy most often involves cranial nerves (CN) III, IV, VI, VII, or II. Disease of CN III, IV, and VI manifests as acute or subacute periorbital pain or headache followed by diplopia. Muscle weakness is typically in the distribution of a single nerve, and pupillary light reflexes are usually spared. Complete spontaneous recovery usually occurs within 3 months.

Facial neuropathy manifests as acute or subacute facial weakness (taste is not normally affected) and can be recurrent or bilateral. Most patients recover spontaneously in 3-6 months.

Anterior ischemic optic neuropathy manifests as acute visual loss or visual-field defects (usually inferior altitudinal). The optic disc appears pale and swollen; flame-shaped hemorrhages may be present.

For more information, see Macular Edema, Diabetic.

Somatic mononeuropathies include focal neuropathies in the extremities caused by entrapment or compression at common pressure points or by ischemia and subsequent infarction. Entrapment and compression tend to occur in the same nerves and at the same sites as in individuals without diabetes. Median nerve entrapment at the wrist (carpal tunnel syndrome) is more common in patients with diabetes and can be treated in the same manner as in patients without diabetes. Symptoms are often bilateral. The susceptibility to ulnar nerve entrapment at the elbow or common peroneal nerve entrapment at the fibular head is not definitely increased among patients with diabetes.

Neuropathy secondary to nerve infarction presents acutely, usually with focal pain associated with weakness and variable sensory loss in the distribution of the affected nerve. Multiple nerves may be affected (mononeuritis multiplex).

Diabetic thoracic radiculoneuropathy presents as burning, stabbing, boring, beltlike, or deep aching pain that usually begins unilaterally and may subsequently become bilateral. Skin hypersensitivity and allodynia (pain with normally innocuous touch) may occur. Numbness follows a dermatomal distribution, most prominent in distal distribution of intercostal nerves. Single or multiple spinal roots are involved. Contiguous territorial extension of symptoms may occur in a cephalad, caudal, or contralateral direction. In the trunk, thoracoabdominal neuropathy or radiculopathy may cause chest and/or abdominal pain in the distribution of thoracic and/or upper lumbar roots. Weakness presents in the distribution of the affected nerve root, such as bulging of the abdominal wall from abdominal muscle paresis (thoracic root). Patients older than 50 years are affected most often; it is more common in diabetes mellitus type 2 and is often associated with significant weight loss. There isoftencoexistingdiabeticdistalsymmetrical polyneuropathy.

Diabetic radiculoplexus neuropathy may occur in the cervical or lumbosacral distributions and is referred to in the literature by various designations, including diabetic amyotrophy, Bruns-Garland syndrome, and diabetic plexopathy. The most frequent initial symptom is sudden, severe, unilateral pain in the hip/lower back or shoulder/neck. Weakness then develops days to weeks later. Atrophy of the limb musculature may occur. Allodynia, paresthesias, and sensory loss are common.

Symptoms usually begin unilaterally and may later spread to the opposite side. Reflexes in the affected limb may be depressed or absent. This condition often occurs in patients older than 50 years with poorly controlled diabetes. It is more common in men than in women. Significant weight loss occurs in 50% of patients. The course is generally monophasic, with improvement over many months; however, some residual deficits often remain.

For more information, see Diabetic Lumbosacral Plexopathyhere.

Previous
Next

Staging

Different clinical neurologic scales can be used to assess the severity of diabetic polyneuropathy.[48]

A common staging scale of diabetic polyneuropathy is as follows[53] :

  • NO - No neuropathy
  • N1a - Signs but no symptoms of neuropathy
  • N2a - Symptomatic mild diabetic polyneuropathy; sensory, motor, or autonomic symptoms; patient able to heel walk
  • N2b - Severe symptomatic diabetic polyneuropathy (as in N2a, but patient unable to heel walk)
  • N3 - Disabling diabetic polyneuropathy
Previous
 
 
Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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

References
  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 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149533.htm. 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 http://www.medscape.com/viewarticle/813976. Accessed: November 12, 2013.

 
Previous
Next
 
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
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.