Diabetic polyneuropathy: an update

To examine current issues in the diagnosis and treatment of diabetic polyneuropathy.

Diabetic neuropathies are common and rising in prevalence with the global burden of type 2 diabetes. Polyneuropathy is also emerging as a complication of impaired glucose tolerance, without frank diabetes. Ideas about the pathogenesis of diabetic polyneuropathy have evolved, and some new pathogenic mechanisms are being considered. These include roles for direct insulin signaling on neurons and axons that transduce growth signals, actions of the cleaved C-peptide product of the insulin prohormone, abnormal signaling by advanced glycation endproducts on neuronal and glial receptors and activation of poly (ADP-ribose) polymerase in microvessels and neurons. Manipulation of these pathways may offer new therapeutic approaches. Ideas about neuronal targets in the treatment of neuropathic pain have also advanced emphasizing abnormal sodium and calcium channel signaling.

Consideration of diabetic polyneuropathy as a unique neurodegenerative condition has generated interest in new pathways involved in its development. A new round of clinical trials that address its pathogenesis may be welcome, as recent attempts have been largely disappointing. In the interim, several forms of therapy for neuropathic pain are available.