Nervous system

Diabetic neuropathy - or more correctly, neuropathies - are the commonest complication of diabetes, although their natural history and the underlying pathogenic mechanisms are still not well understood. The multiple manifestations of neuropathy make it particularly difficult to evaluate and treat, both in clinical care and in clinical research. The greatest morbidity from this complication is attributable to diabetic peripheral neuropathy and diabetic autonomic neuropathy, and this section will focus upon these two manifestations. Areas to be covered include classification , natural history, pathogenesis, recommended current assessments and treatment.


Diabetic neuropathy is the most common chronic complication of diabetes [1][2][3][4][5][6], and represents a clinically diverse group of disorders having differing anatomic distribution, clinical course, and underlying pathophysiology. Diabetic neuropathy is diagnosed after the exclusion of other causes, and it is ultimately thought to reflect metabolic and microvascular factors that result in axonal degeneration of large and small nerve fibers.

The specific presentation of diabetic neuropathy reflects the distribution and size of nerve fibers involved, most commonly presenting as a distal symmetric sensory or sensorimotor neuropathy (diabetic peripheral neuropathy, DPN) and autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN). Diabetic neuropathies are a major cause of disability[1], associated with reduced quality of life [7][8], and high mortality [9][10].

Pain is the outstanding complaint in most patients, but many patients may be completely asymptomatic. Painful symptoms are frequently refractory to treatment, and loss of protective sensation heightens the risk for foot ulceration and lower extremity amputations [3][11][12][13][14].

The late sequelae of neuropathy are well recognized, with foot problems including ulceration [15] and Charcot neuroarthropathy [13], or severe manifestations of autonomic neuropathy [16][17] representing the most common cause of hospitalization amongst diabetic patients in most western countries.

Treatment has traditionally focused on control of hyperglycemia as a means of slowing progression or delaying onset, on targeting potential pathogenetic mechanisms, and on pain reduction.

Definition of Diabetic Neuropathy

Diabetic neuropathy (DN) is a common chronic complication of diabetes (type 1 or type 2), characterized by the presence of a broad spectrum of symptoms and/or signs of peripheral nerve dysfunction and/or autonomic nerve dysfunction. It is diagnosed after the exclusion of other causes. Frequently, however, people with DN are asymptomatic.

Although there are no major structural differences in nerve pathology between the 2 main types of diabetes, type 1 diabetes (T1DM) and type 2 diabetes (T2DM), clinical differences do exist.

Classification of Diabetic Neuropathies

Many classification systems for the neuropathies have been proposed over the years: some are based on presumed etiology whereas others refer to topographic features or disease pathogenesis. Recently, the International Toronto Expert Panel on Diabetic Neuropathy has provided an update on polyneuropathies associated with diabetes. While this panel endorsed the classifications previously published [18], it also provided evidence that generalized diabetic peripheral neuropathy (DPN) can be further classified into 2 major subgroups [19]:

  • Typical DPN - a chronic, symmetrical, length-dependent (longer nerves affected first in the most distal segments) sensorimotor polyneuropathy. It is thought to be the commonest variety of DPN from cohort and population-based epidemiologic studies.
  • Atypical DPN - may develop at any time during the course of a patient's diabetes mellitus. Onset of symptoms may be acute, subacute, or chronic, but the course is usually monophasic or fluctuating over time, tending to preferentially involve small sensory and autonomic nerve fibers.

The classification shown below was adopted by the American Diabetes Association [1][3].

Classification of Diabetic Neuropathies

Polyneuropathy Mononeuropathy
Sensory: Acute sensory, Chronic sensorimotor Isolated peripheral, Mononeuritis multiplex, Truncal
Autonomic: Cardiovascular, Gastrointestinal, Genitourinary, Other
Proximal motor (amyotrophy)


  1. ^ Tesfaye S, et al. Diabetic update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010;2285-2293

  2. ^ Boulton AJ, et al. The Diabetic Neuropathies: Reports from the Diabetic Neuropathy Expert Panel Meeting on Neuropathy, Toronto, October Introduction. Diabetes Metab Res Rev 2011;27:617-619

  3. ^ Boulton AJ, et al. Diabetic a statement by the American Diabetes Association. Diabetes Care 2005;956-962

  4. ^ Pirart J: Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (3rd and last part). Diabetes & metabolism 1977;3:245-256

  5. ^ Dyck PJ, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based the Rochester Diabetic Neuropathy Study. Neurology 1993;817-824

  6. ^ Dyck PJ et al. The Rochester Diabetic Neuropathy SDesign, criteria for types of neuropathy, selection bias, and reproducibility of neuropathic tests. Neurology 1991;799-807

  7. ^ Vileikyte L: Diabetic foot ulcers: a quality of life issue. Diabetes Metab Res Rev 2001;17:246-249

  8. ^ Vileikyte L et al. Diabetic peripheral neuropathy and depressive the association revisited. Diabetes Care 2005;2378-2383

  9. ^ Maser RE et al. The association between cardiovascular autonomic neuropathy and mortality in individuals with a meta-analysis. Diabetes Care 2003;1895-1901

  10. ^ Pop-Busui R et al. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010;1578-1584

  11. ^ Boulton AJ et al. Clinical practice. Neuropathic diabetic foot ulcers. N Engl J Med 2004;48-55

  12. ^ Boulton AJ et al. Diabetic somatic neuropathies. Diabetes Care 2004;1458-1486

  13. ^ Boulton AJ et al. The global burden of diabetic foot disease. Lancet 2005;1719-1724

  14. ^ Bril V et al. Evidence-based Treatment of painful diabetic report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. PM R 2011;345-352, 352 e341-321

  15. ^ Partanen J et al. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. NEnglJMed 1995;89-94

  16. ^ Kempler P et al. Gastrointestinal autonomic neuropathy, erectile-, bladder- and sudomotor dysfunction in patients with diabetes clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 2011;665-677

  17. ^ Pop-Busui R: What do we know and we do not know about cardiovascular autonomic neuropathy in diabetes. J Cardiovasc Transl Res 2012;5:463-478

  18. ^ Boulton AJ et al. Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy. Diabet Med 1998;508-514

  19. ^ Dyck PJ et al. Diabetic PUpdate on Research Definition, Diagnostic Criteria and Estimation of Severity. Diabetes Metab Res Rev 2011;


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