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Literature review current through: Apr 2018. | This topic last updated: Dec 15, 2016.
Symptoms and signs — The earliest signs of diabetic polyneuropathy probably reflect the
gradual loss of integrity of both large myelinated and small myelinated and unmyelinated
nerve fibers:
● Impairment of pain, light touch, and temperature is secondary to loss of small fibers
Decreased or absent ankle reflexes occur early in the disease, while more widespread
loss of reflexes and motor weakness are late findings.
Distal motor axonal loss results in atrophy of intrinsic foot muscles and an imbalance
between strength in toe extensors and flexors. This ultimately leads to chronic
metatarsal-phalangeal flexion (claw-toe deformity) which shifts weight to the metatarsal
heads [3]. This weight shift results in formation of calluses that can fissure, become
infected and ulcerate. There may also be other arthropathic changes including collapse
of the arch of the midfoot and bony prominences, leading to Charcot arthropathy,
fragmentation and sclerosis of bone, new bone formation, subluxation, dislocation, and
stress fractures. (See "Diabetic neuropathic arthropathy".)
Natural history — The rationale for regular monitoring (see 'Monitoring' below) is the
observation that the incidence of diabetic neuropathy (and other microvascular and
macrovascular complications) increases over time. This was illustrated by a study from
Finland that evaluated the natural history of peripheral neuropathy in patients with newly
diagnosed type 2 diabetes [3]. Polyneuropathy was diagnosed on the basis of both
clinical (pain and paresthesia) and electrodiagnostic (nerve conduction velocity and
response-amplitude values) criteria. The prevalence of definite or probable
polyneuropathy progressively increased from 8.3 percent at baseline to 41.9 percent at
10 years; comparable values in normal subjects were 2.1 and 5.8 percent, respectively.
In a later population-based study from Australia that evaluated patients with type 2
diabetes who had an average disease duration of about eight years, the prevalence of
painful diabetic polyneuropathy was 26.4 percent [4].
A third consensus panel convened in Toronto in 2009 and advocated that, for controlled
clinical trials and epidemiologic studies of diabetic neuropathy, nerve conduction studies
are needed for accurate assessment, and are coupled with assessments of symptoms
and signs [8].
Screening tests — The San Antonio Consensus [6], the Mayo Clinic criteria and the
Toronto criteria [8] are thorough and appropriate for research purposes. However, they
are not practical in routine clinical practice. The need to identify simplified criteria has
resulted in the development of several simple screening tests. Two will be discussed:
one from the United Kingdom [9] and one which we developed at Michigan [10]. These
simple tools used to diagnose diabetic neuropathy do not include electrodiagnostic
assessments with nerve conduction studies or quantitative sensory testing. These are
discussed later. (See 'Electrodiagnostic tests' below.)
● What is the timing of symptoms? Worse at night (2 points); present day and night (1
point); present only during the day (0 points). Maximum is 2 points.
● How are symptoms relieved? Walking around (2 points); standing (1 point); sitting or
lying or no relief (0 points). Maximum is 2 points.
● 0 to 2 points: Normal
● What is the Achilles tendon reflex? Absent (2 points for each foot); present with
reinforcement (1 point for each foot).
● What is pin prick sensation? Absent or reduced (1 point for each foot).
● 0 to 2 points: Normal
● Do the feet show dry skin, callus, fissure, infection or deformities? The presence of
any of these indicators of neuropathy is scored as one point and an additional point
is added if an ulcer is present.
● What is the vibration sense on the dorsum of the great toes? Reduced (0.5 points);
absent (1 point).
● What is the Achilles tendon reflex? Absent (1 point); present with reinforcement (0.5
points).
This test was standardized against the San Antonio Consensus criteria. A score greater
than 2 indicated neuropathy with both a high specificity (95 percent) and sensitivity (80
percent) [10]. The Michigan Neuropathy Screening Instrument can be administered by
any health care professional involved in the treatment of diabetic patients.
Tuning fork test — A simple test using a 128 Hz tuning fork to examine vibration
perception can be used to screen for diabetic polyneuropathy [12]. (See "The detailed
neurologic examination in adults".)
A 128 Hz tuning fork is placed on the interphalangeal joint of the right hallux.
When the patient feels vibration at the hallux, the still vibrating tuning fork is
immediately placed at the dorsal wrist, and the patient is asked to compare the
strength of vibration at the two sites.
This tuning fork test has widespread utility in clinical practice because it is simple, brief,
valid, and reliable [12,13].
A patient with any constellation of these atypical presenting symptoms or signs requires
electrodiagnostic testing for an accurate diagnosis.
Staging test
● 41 percent had mild neuropathy: Score ≤12 and abnormal conduction in two nerves.
● 29 percent had moderate neuropathy: Score ≤29 and abnormal conduction in three
or four nerves.
Certain forms of neuropathy (other than diabetic neuropathy) occur more frequently in
patients with diabetes than in the general population and should be excluded. These
include chronic inflammatory demyelinating polyneuropathy (CIDP) and neuropathy due
to vitamin B12 deficiency, hypothyroidism, and uremia [14].
Although uncommon, there are several types of acute painful diabetic neuropathy
syndromes. These are:
● Treatment-induced diabetic neuropathy that presents in the setting of rapid glycemic
control (see "Epidemiology and classification of diabetic neuropathy", section on
'Treatment-induced neuropathy of diabetes')
● Diabetic anorexia, a diabetic neuropathy that is seen with intentional weight loss
● All patients with diabetes should be screened for neuropathy at diagnosis of type 2
diabetes and five years after diagnosis of type 1 diabetes.
● After initial screening, all patients should be screened at least annually by examining
sensory function in the feet and checking ankle reflexes. One or more of the
following tests can be used to assess sensory function:
• Pinprick
• Temperature
● At each diabetes care clinic visit, the feet should be examined for neuropathic
deformities, infection and ulceration, and the footwear should be inspected. (See
"Evaluation of the diabetic foot".)
● The patient should carefully inspect his or her feet daily [10].
● All patients with neuropathy, including those who are asymptomatic, should receive
foot care education and consideration for podiatric referral.
Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword(s) of
interest.)
● Basics topics (see "Patient education: Nerve damage caused by diabetes (The
Basics)")
● Beyond the Basics topics (see "Patient education: Diabetic neuropathy (Beyond the
Basics)")
● For the diagnosis of diabetic polyneuropathy, both the San Antonio Consensus and
the Mayo Clinic criteria are thorough and appropriate for research purposes.
However, they are not practical in routine clinical practice. Simplified criteria have
been developed for clinical use (see 'Criteria for diagnosis' above):
● Diabetic neuropathy should be suspected in any patient with type 1 diabetes of more
than five years duration and in all patients with type 2 diabetes. In addition,
neuropathy due to prediabetes should be suspected in any patient presenting with
"idiopathic" painful neuropathy. Because of the potentially severe complications,
including amputation for infected, nonhealing ulcers, early detection of diabetic
polyneuropathy is important. (See 'Monitoring' above.)
REFERENCES
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types of diabetic neuropathy, retinopathy, and nephropathy in a population-
based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993;
43:817.
2. Franse LV, Valk GD, Dekker JH, et al. 'Numbness of the feet' is a poor indicator
for polyneuropathy in Type 2 diabetic patients. Diabet Med 2000; 17:105.
3. Partanen J, Niskanen L, Lehtinen J, et al. Natural history of peripheral
neuropathy in patients with non-insulin-dependent diabetes mellitus. N Engl J
Med 1995; 333:89.
4. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of
painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006;
29:1518.
5. MULDER DW, LAMBERT EH, BASTRON JA, SPRAGUE RG. The neuropathies
associated with diabetes mellitus. A clinical and electromyographic study of
103 unselected diabetic patients. Neurology 1961; 11(4)Pt 1:275.
6. Consensus statement: Report and recommendations of the San Antonio
conference on diabetic neuropathy. American Diabetes Association American
Academy of Neurology. Diabetes Care 1988; 11:592.
7. England JD, Gronseth GS, Franklin G, et al. Distal symmetric polyneuropathy: a
definition for clinical research: report of the American Academy of Neurology,
the American Association of Electrodiagnostic Medicine, and the American
Academy of Physical Medicine and Rehabilitation. Neurology 2005; 64:199.
8. Dyck PJ, Albers JW, Andersen H, et al. Diabetic polyneuropathies: update on
research definition, diagnostic criteria and estimation of severity. Diabetes
Metab Res Rev 2011; 27:620.
9. Young MJ, Boulton AJ, MacLeod AF, et al. A multicentre study of the prevalence
of diabetic peripheral neuropathy in the United Kingdom hospital clinic
population. Diabetologia 1993; 36:150.
10. Feldman EL, Stevens MJ, Thomas PK, et al. A practical two-step quantitative
clinical and electrophysiological assessment for the diagnosis and staging of
diabetic neuropathy. Diabetes Care 1994; 17:1281.
11. Dyck PJ, Kratz KM, Lehman KA, et al. The Rochester Diabetic Neuropathy Study:
design, criteria for types of neuropathy, selection bias, and reproducibility of
neuropathic tests. Neurology 1991; 41:799.
12. Meijer JW, Smit AJ, Lefrandt JD, et al. Back to basics in diagnosing diabetic
polyneuropathy with the tuning fork! Diabetes Care 2005; 28:2201.
13. Kanji JN, Anglin RE, Hunt DL, Panju A. Does this patient with diabetes have
large-fiber peripheral neuropathy? JAMA 2010; 303:1526.
14. Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the
American Diabetes Association. Diabetes Care 2005; 28:956.
15. Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy:
mechanisms to management. Pharmacol Ther 2008; 120:1.
16. Singleton JR, Smith AG, Russell J, Feldman EL. Polyneuropathy with Impaired
Glucose Tolerance: Implications for Diagnosis and Therapy. Curr Treat Options
Neurol 2005; 7:33.