The Diabetic Neuropathies

Practical and Rational Therapy

J. Robinson Singleton, M.D.; A. Gordon Smith, M.D.


Semin Neurol. 2012;32(3):196-203. 

In This Article

Clinical Features of Diabetic Neuropathy

Distal symmetric polyneuropathy (DSP) is the most common neuropathic complication of diabetes; 50% or more of patients develop DSP, and up to 20% have clinical features of neuropathy at the time of diabetes diagnosis. Distal symmetric polyneuropathy causes "positive" and "negative" sensory symptoms in a length-dependent pattern, affecting the toes and distal foot, spreading over time to the ankle and proximally. Patients may describe numbness, or may be unaware of their sensory loss until demonstrated on exam. Positive symptoms consist of abnormal spontaneous "paresthesias" such as pricking, tingling, or burning; "allodynia," perception of nonpainful stimuli as painful; or "hyperalgesia," inappropriate exaggeration of painful sensation. Two in five diabetic patients with DSP experience neuropathic pain, which is often the principal source of disability. The pain is often described as "deep aching," "burning," "electric," "tingling," or "sharp." Although pain frequently limits activities and is worse with walking, it is most severe at nighttime and sometimes inhibits sleep. Pain is typically moderate to severe. The average pain intensity in a survey of 105 painful DSP patients was 5.8/10.[1]

Distal symmetric polyneuropathy is a major cause of disability and reduced quality of life. Those with severe neuropathy may suffer painless injury. With more advanced disease, motor denervation can result in foot intrinsic muscle atrophy, exaggerated foot arch, and hammer toes. Foot and ankle instability due to weakness and reduced proprioception leads to falls, sprains, foot bone fractures, and other orthopedic injuries. Loss of protective sensation combined with altered sweating and poor wound healing predispose patients with DSP to foot ulcers, Charcot foot abnormalities, and amputation.

Evaluation should proceed from focused questions about pain, paresthesias, sensory loss, and weakness to an exam tailored to detection of length-dependent nerve injury. Strength is often normal, but there may be atrophy of foot muscles. Atrophy of hand muscles is more often due to focal compressive mononeuropathies of ulnar or median nerves. Deep tendon reflexes are characteristically reduced or absent at the ankles and well-preserved distal reflexes in the face of other neuropathic features should prompt consideration of a structural myelopathy or a dorsal column neuropathy, such as B12 deficiency. Sensory testing should evaluate the severity (absence vs reduced) and distribution of sensory loss to modalities associated with small unmyelinated (pain and autonomic) and large myelinated (proprioceptive, touch, and motor) fibers. Pin sensation can be rapidly mapped to establish the proximal extent of sensory deficit. Timed vibration with a 128 Hz tuning fork provides a semiquantitative measure with a broad dynamic range. Nerve conduction studies and electromyography should be considered in patients who present with rapidly progressive symptoms or significant asymmetry or motor involvement.

Diabetic autonomic neuropathy is common, but underrecognized. Most patients with diabetic autonomic neuropathy do not have symptoms of a generalized dysautonomia. Instead, many are asymptomatic, or present with vague symptoms of dizziness, poor balance, nausea, abdominal pain, or sexual dysfunction. Thus, a high index of suspicion for diabetic autonomic neuropathy is required. Diabetic autonomic neuropathy significantly increases risk for cardiac death and causes disability due to orthostatic hypotension, syncope, erectile dysfunction, gastroparesis, diarrhea, and hypoglycemia. Coronary artery disease is often evaluated because it predicts greater all-cause mortality and can be detected using simple tests of vagal heart rate response to deep breathing or Valsalva. Erectile dysfunction is reported by 27% of men with newly diagnosed diabetes, and in 20 to 40% of men with metabolic syndrome and prediabetes.[2] Sensitive tests for defects in peripheral sweat generation in response to acetylcholine find reduced responsiveness in a quarter of newly diagnosed diabetic patients.