title: Foot temperature in diabetic polyneuropathy: innocent bystander or unrecognized accomplice?
abstract: OBJECTIVE
  To explore mechanisms by which temperature could influence the pathogenesis and symptoms of diabetic polyneuropathy.
  
  
  METHODS
  We conducted a literature review attempting to identify mechanisms by which diabetic polyneuropathy could be affected by temperature.
  
  
  RESULTS
  Cooling can theoretically hasten the progression of diabetic polyneuropathy through several different mechanisms. Specifically, cooling can enhance neuronal ischaemia, increase formation of reactive oxygen species, slow axonal transport, increase protein kinase C activity, and interfere with immune function. Short-term temperature fluctuations (both warming and cooling) can initiate and exacerbate neuropathic pain by causing neuronal hyperexcitability and functional deafferentation. Although normal fluctuations of distal extremity temperature may be sufficient for these effects, impaired thermoregulation may make the distal extremities more susceptible to temperature extremes. Eventually, a 'vicious cycle' may ensue, resulting in neuronal deterioration with further disruption of temperature regulation. Limited epidemiological data suggest a higher prevalence of diabetic polyneuropathy in populations living in colder locations, supporting our hypothesis.
  
  
  CONCLUSIONS
  Variations in foot temperature may play an important but as yet unrecognized role in the development and symptoms of diabetic polyneuropathy. Further basic and clinical research exploring this concept could help elucidate the natural history of diabetic polyneuropathy and lead to novel therapeutic strategies.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. srutkove@bidmc.harvard.edu
authors.forename: S B
authors.initials: SB
authors.lastname: Rutkove
authors.forename: K M
authors.initials: KM
authors.lastname: Chapman
authors.forename: J A
authors.initials: JA
authors.lastname: Acosta
authors.forename: J E
authors.initials: JE
authors.lastname: Larrabee
mesh_terms: D001831:Body Temperature; D001833:Body Temperature Regulation; D003080:Cold Temperature; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D018450:Disease Progression; D005528:Foot / Q000098:blood supply / Q000503:physiopathology*; D006801:Humans; D007511:Ischemia / Q000150:complications / Q000503:physiopathology; D010146:Pain / Q000209:etiology; D017933:Peripheral Nervous System / Q000098:blood supply