Diabetic Polyneuropathy


Diabetic polyneuropathy is a neurological disease of the peripheral nerves due to diabetes. Diabetic polyneuropathy is accompanied by pain and/or deficits based on dysfunction of the peripheral nerves.


Diabetic polyneuropathy can be the result of a direct toxic effect of glucose on the nerve cells.  Damage to the neural structures (central and peripheral) is accompanied by microvascular dysfunction affecting the vasa nervorum. The latter is secondary to oxidative stress due to hyperglycaemia and other disturbances of the metabolic balance. Therefore, diabetic patients whose anti-diabetic medication is insufficiently regulated, have a greater chance of developing a neuropathy and/or of neuropathic pain. Moreover, other cardiovascular factors, such as hypertension and, more importantly, hyper- and dyslipidemia (high level triglycerides and low level HDL-cholesterol) can play a role.

Diabetic polyneuropathy is seen in various forms:

  • Distal and symmetric sensory neuropathy. Depending on the nerve fibres affected, this form is found in the small C fibres, thick Aδ fibres and Aβ fibres.
  • Motor neuropathy with damage to the Aδ fibres (mono-neuropathy and multiplex neuropathy).
  • Autonomic neuropathy (digestive, urogenital, cardiac, cutaneous affection related to distal sensory neuropathy due to damage to the C fibres).
  • Inflammatory neuropathy (due to infiltration of lymph and plasma cells with damage to the vasa nervorum and myelin).

Signs and symptoms

More than 80% of diabetes patients with polyneuropathy have a distal symmetric form of this affection. The symptoms usually start in the feet and gradually move higher up the legs. The longest nerves are affected first, which points to a Length-Dependent Diabetic Polyneuropathy (LDDP). The short nerves will follow later and, in extreme cases, the trunk may become affected.

As soon as the polyneuropathy reaches the level of the knees, the hands are frequently involved.  Although an interval can exist between the occurrence of diabetes and the first manifestations of this LDDP, polyneuropathy can be the first symptom of diabetes.

The first signs and symptom are hypoalgesia, burning feet particularly during the night increasing with touch, and paraesthesia of the feet. Paroxysmal shooting pains also occur.

Despite the existence of moderate pain, sensory changes can be present. Together with trophic disorders and bad wound healing, sensory changes make the diagnosis of diabetic polyneuropathy likely.  When there is LDDP, recovery of the polyneuropathy is unlikely.


Physical Examination

A general physical examination and extensive neurological examination are very important. The following tests should definitely be included in the neurological examination: (1) testing of all sensory qualities of the arms and legs (attention should be paid to symmetry and to the distal proximal gradient); (2) reflexes; and (3) strength tests.

One of the characteristics of the neurological examination is a reduced sense of touch and pinprick, together with a decreased sense of temperature (vital sensibility). Reduction of the gnostic sensibility can result in a diminished sense of position of the joints, in particular of the feet, with a consequent inclination to fall down. Allodynia and hyperalgesia may be present.

Additional Somatic Diagnostics

  • Electrophysiology (sensory and motor nerve conduction) evaluation in diabetic polyneuropathy is mandatory in order to demonstrate axonal degeneration and demyelinisation. However, a normal result does not exclude polyneuropathy and must always be combined with a good clinical assessment.
  • Small non-myelinated fibres should be included in nerve conduction examination. Laser-evoked potentials can have an additional diagnostic value.
  • In addition, vascular evaluation at a micro-level is indicated in order to demonstrate a micro-angiopathy.
  • In diabetes, autonomic disorders, such as orthostatic hypotension, cardiac arrhythmia, gastric paresis, intestinal and urinary bladder disorders, pupil abnormalities, etc., can occur, making further evaluation necessary.
  • An abnormality of the spinal cord diameter can be indicative of generalisation of the polyneuropathy.
  • RAND-36 (quality of life)
  • VAS-Pain (maximal, minimal, actual, average/week)
  • PCS (catastrophising)
  • HADS (fear and depression)

Additional Psycho-cognitive Diagnostics

Multidisciplinary Treatment

Whether or not somatic treatment is indicated is based on the pain diagnosis. Based on the findings of the pain questionnaires, additional diagnostics and/or multidisciplinary treatment consisting of various non-somatic treatments may be necessary.

Non-somatic Treatment

Somatic Treatment

Pharmacological treatment:

  • Tricyclic antidepressants
  • Anticonvulsives: carbamazepine, oxcarbazepine, gabapentine and pregabaline.
  • Meticulous regulation of blood glucose levels

Other Treatments

Interventional Pain Treatment


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