Practice Essentials
Diabetic neuropathy is the most common complication of diabetes mellitus (DM), affecting as many as 50% of patients with type 1 and type 2 DM. Diabetic peripheral neuropathy involves the presence of symptoms or signs of peripheral nerve dysfunction in people with diabetes after other possible causes have been excluded.
In some cases, patients are symptomatic long before routinely performed clinical examination reveals abnormalities. Of all treatments, tight and stable glycemic control is probably the most important for slowing the progression of neuropathy.
Signs and symptoms of diabetic neuropathy
In type 1 DM, distal polyneuropathy typically becomes symptomatic after many years of chronic prolonged hyperglycemia, whereas in type 2, it may be apparent after only a few years of known poor glycemic control or even at diagnosis. Symptoms include the following:
Sensory – Negative or positive, diffuse or focal; usually insidious in onset and showing a stocking-and-glove distribution in the distal extremities
Motor – Distal, proximal, or more focal weakness, sometimes occurring along with sensory neuropathy (sensorimotor neuropathy)
Autonomic – Neuropathy that may involve the cardiovascular, gastrointestinal, and genitourinary systems and the sweat glands
Physical examination should include the following assessments:
Peripheral neuropathy testing – Gross light touch and pinprick sensation; vibratory sense; deep tendon reflexes; strength testing and muscle atrophy; dorsal pedal and posterior tibial pulses; skin assessment; Tinel testing; cranial nerve testing
Autonomic neuropathy testing – Objective evaluation of cardiovagal, adrenergic, and sudomotor function in a specialized autonomic laboratory; may be preceded by bedside screening to assess supine and upright blood pressure and heart rate, with measurement of sinus arrhythmia ratio
Two classification systems for diabetic neuropathy are the Thomas system and the symmetrical-versus-asymmetrical system. The Thomas system (modified) is as follows:
Hyperglycemic neuropathy
Generalized symmetrical polyneuropathies
Sensory neuropathy
Sensorimotor neuropathy
Autonomic neuropathy
Focal and multifocal neuropathies
Superimposed chronic inflammatory demyelinating polyneuropathy
Distal symmetrical sensorimotor polyneuropathy is commonly defined according to the following 3 key criteria:
The patient must have diabetes mellitus consistent with a widely accepted definition
Severity of polyneuropathy should be commensurate with duration and severity of diabetes
Other causes of sensorimotor polyneuropathy must be excluded
Pure autonomic diabetic neuropathy is rare.
Asymmetrical neuropathies 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
Diabetic polyneuropathy is commonly staged as follows:
NO – No neuropathy
N1a – Signs but no symptoms of neuropathy
N2a – Symptomatic mild diabetic polyneuropathy; sensory, motor, or autonomic symptoms; patient is able to heel-walk
N2b – Severe symptomatic diabetic polyneuropathy; patient is unable to heel-walk
N3 – Disabling diabetic polyneuropathy
See Clinical Presentation for more detail.
Diagnosis of diabetic neuropathy
Laboratory tests that may be helpful include the following:
Fasting plasma glucose
Hemoglobin A1c
Complete blood 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 (for anemia)
Sequential multiple analysis-7 (renal function and electrolyte imbalances)/complete metabolic panel (CMP)
Other diagnostic modalities that may be considered are as follows:
Electromyography and nerve conduction velocity testing
Electrophysiologic studies
Magnetic resonance imaging
Computed tomography (including single-photon emission computed tomography)
Nuclear imaging
Doppler imaging
Microdialysis
Electrocardiography
Nerve and skin biopsy (now rarely recommended for clinical purposes)
See Workup for more detail.
Management of diabetic neuropathy
Key components of the management of diabetic neuropathy include the following:
Foot care, including regular follow-up, patient education, and referral as appropriate
Tight, stable glycemic control (most important for slowing progression of neuropathy)
Pain management (eg, with pregabalin, gabapentin, sodium valproate, dextromethorphan, morphine sulfate, tramadol, oxycodone, duloxetine, topical capsaicin, transdermal lidocaine)
Treatment of diabetic gastroparesis (eg, with erythromycin, cisapride [not available in the United States], metoclopramide, polyethylene glycol 3350, tegaserod [currently available only on an emergency basis])
Experimental therapies include aldose reductase inhibitors, alpha-lipoic acid, actovegin, and spinal cord stimulators.
Treatment of autonomic dysfunction must address the following:
Erectile dysfunction
Orthostatic hypotension
Gustatory sweating
Surgical treatment may be considered as follows:
Aggressive debridement or amputation for recalcitrant foot necrosis or infection
Jejunostomy for intractable gastroparesis
Implantation of a penile prosthesis for ongoing impotence
Bracing, special boots, or, in some cases, surgery for Charcot foot
Pancreatic transplantation for diabetes with end-stage renal disease
See Treatment and Medication for more detail.