-
If you are citizen of an European Union member nation, you may not use this service unless you are at least 16 years old.
-
You already know Dokkio is an AI-powered assistant to organize & manage your digital files & messages. Very soon, Dokkio will support Outlook as well as One Drive. Check it out today!
|
Diabetic Neuropathies
This version was saved 15 years, 8 months ago
View current version Page history
Saved by Robert Rushakoff, MD
on July 8, 2008 at 10:40:30 pm
Diabetic Neuropathies
Aaron Vinik, MD
Carolina Casellini, M.D.
Abhijeet Nakave, MBBS.
Chhaya Patel, MBBS.
Diabetic neuropathy (DN) is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care . It is the most common form of neuropathy in the developed countries of the world, accounts for more hospitalizations than all the other diabetic complications combined, and is responsible for 50-75% of non-traumatic amputations . DN is a set of clinical syndromes that affect distinct regions of the nervous system, singly or combined. It may be silent and go undetected, while exercising its ravages or it may present with clinical symptoms and signs that although nonspecific and insidious with slow progression but also mimic those seen in many other diseases. It is, therefore, diagnosed by exclusion. Unfortunately both endocrinologists and non endocrinologists have not been trained to recognize the condition , and even when symptomatic less than one third of physicians recognize the cause or discuss this with their patients
The true prevalence is not known and reports vary from 10% to 90% in diabetic patients, depending on the criteria and methods used to define neuropathy . Twenty five percent of patients attending a diabetes clinic volunteered symptoms; 50 % were found to have neuropathy after a simple clinical test such as the ankle jerk or vibration perception test; almost 90% tested positive to sophisticated tests of autonomic function or peripheral sensation . Neurologic complications occur equally in type 1 and type 2 diabetes mellitus and additionally in various forms of acquired diabetes . The major morbidity associated with somatic neuropathy is foot ulceration, the precursor of gangrene and limb loss. Neuropathy increases the risk of amputation 1.7 fold; 12 fold, if there is deformity (itself a consequence of neuropathy), and 36 fold, if there is a history of previous ulceration . Each year 96,000 amputations are performed on diabetic patients in the United States, yet up to 75% of them are preventable . Globally there is an amputation every 30 seconds. Diabetic neuropathy also has a tremendous impact on patients’ quality of life predominantly by causing weakness, ataxia and incoordination predisposing to falls and fractures Once autonomic neuropathy sets in, life can become quite dismal and the mortality rate approximates 25-50% within 5-10 years .
DN is defined as the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes. A careful clinical examination is needed for the diagnosis, since asymptomatic neuropathy is common . A minimum of two abnormalities (symptoms, signs, nerve conduction abnormalities, quantitative sensory tests or quantitative autonomic tests) is required for diagnosis and, for clinical studies, one of theses two abnormalities should include quantitative tests or electrophysiology . Standardized testing using nerve symptom scores and nerve impairment scores to quantify weakness, loss of reflexes and sensory deficits has proved invaluable in diagnosis and monitoring of progress and is indispensable for clinical trials.
Box 1 describes the classification proposed by Thomas and modified by us . It is important to note that different forms of DN often coexist in the same patient (e.g. distal polyneuropathy and carpal tunnel syndrome)
Table A. Classification of diabetic neuropathies.
Rapidly reversible
|
Generalized symmetric polyneuropathy
-
Acute sensory neuropathy
-
Chronic sensorimotor neuropathy or distal symmetric polyneuropathy (DPN)
-
Small-fiber neuropathy
-
Large-fiber neuropathy
-
Autonomic neuropathy
|
Focal and multifocal neuropathies
-
Focal-limb neuropathy
-
Cranial neuropathy
-
Proximal-motor neuropathy (amyotrophy)
-
Truncal radiculoneuropathy
-
Coexisting chronic inflammatory demyelinating neuropathy (CIDP)
|
The epidemiology and natural history of DN remain poorly defined, in part because of variable criteria for the diagnosis, failure of many physicians to recognize and diagnose the disease and lack of standardized methodologies used for the evaluation of these patients .It has nonetheless been estimated that 50% of patients with diabetes have DN and 2.7 million have painful neuropathy in the US. DN is grossly under diagnosed and under treated The natural history of neuropathies separates them into two very distinctive entities, namely those which progress gradually with increasing duration of diabetes, and those which remit usually completely. Sensory and autonomic neuropathies generally progress, while mononeuropathies, radiculopathies, and acute painful neuropathies, although symptoms are severe, are short-lived and tend to recover . Progression of DN is related to glycemic control in both type 1 and type 2 diabetes . It appears that the most rapid deterioration of nerve function occurs soon after the onset of type 1 diabetes and within 2-3 years there is a slowing of the progress with a shallower slope to the curve of dysfunction. In contrast, in type 2 diabetes, slowing of nerve conduction velocities (NCVs) may be one of the earliest neuropathic abnormalities and often is present even at diagnosis . After diagnosis, slowing of NCV generally progresses at a steady rate of approximately 1 m/sec/year, and the level of impairment is positively correlated with duration of diabetes. Although most studies have documented that symptomatic patients are more likely to have slower NCVs than patients without symptoms, these do not relate to the severity of symptoms. In a long term follow up study of type 2 diabetes patients , electrophysiologic abnormalities in the lower limb increased from 8% at baseline to 42% after 10 years, with a decrease in sensory and motor amplitudes, indicating axonal destruction, was more pronounced than the slowing of the NCVs. Using objective measures of sensory function such as the vibration perception threshold test, the rate of decline in function has been reported as 1-2 vibration units/year. However, there now appears to be a decline in this rate of evolution. It appears that host factors pertaining to general health and nerve nutrition are changing. This is particularly important when doing studies on treatment of DN, which have always relied on differences between drug treatment and placebo and have apparently been successful because of the decline in placebo-treated patients . Recent studies have pointed out the changing natural history of DN with the advent of therapeutic lifestyle change, and the use of statins and ACE inhibitors, which have slowed the progression of DN and drastically changed the requirements for placebo-controlled studies. . It is also important to recognize that DN is a disorder wherein the prevailing abnormality is loss of axons that electrophysiologically translates to a reduction in amplitudes and not conduction velocities, and changes in NCV may not be an appropriate means of monitoring progress or deterioration of nerve function. Small, unmyelinated nerve fibers are affected early in DM and are not reflected in NCV studies. Other methods, that do not depend on conduction velocities, such as quantitative sensory testing, autonomic function testing or skin biopsy with quantification of intraepidermal nerve fibers (IENF), are necessary to identify these patients
Causative factors include persistent hyperglycemia, microvascular insufficiency, oxidative and nitrosative stress, defective neurotrophism, and autoimmune-mediated nerve destruction Figure 1 summarizes our current view of the pathogenesis of DN . Detailed discussion of the different theories is beyond the scope of this review and the reader is referred to several excellent recent reviews. However, DN is a heterogeneous group of conditions with widely varying pathology, suggesting differences in pathogenic mechanisms for the different clinical syndromes. Recognition of the clinical homologue of these pathologic processes is the first step in achieving the appropriate form of intervention.
Diabetic Neuropathies
|
Tip: To turn text into a link, highlight the text, then click on a page or file from the list above.
|
|
|
|
|
Comments (0)
You don't have permission to comment on this page.