title: Axonal dysfunction prior to neuropathy onset in type 1 diabetes.
abstract: BACKGROUND
  The present study was undertaken to determine whether there were changes evident in axonal membrane function prior to the onset of neuropathy in patients with type 1 and type 2 diabetes.
  
  
  METHODS
  From a cohort of 110 consecutive referrals, nerve excitability was investigated in 40 diabetic patients without clinical evidence of neuropathy (20 type 1 diabetic patients and 20 type 2 diabetic patients). Groups were matched for gender, disease duration and HbA(1c). Studies were also undertaken in two control groups, younger controls and older controls, matched for age and gender with the diabetic cohorts.
  
  
  RESULTS
  Subjects with type 1 diabetes demonstrated significant nerve excitability abnormalities when compared with younger normal controls. Specifically, type 1 subjects showed a significant reduction at multiple time points in both depolarising and hyperpolarising threshold electrotonus. Additionally, the relative refractory period was prolonged (type 1, 3.19 ms; younger normal controls, 3.0 ms; p < 0.05) and superexcitability was reduced (type 1, -23.12%; younger normal controls, -26.37%; p < 0.05), consistent with axonal membrane depolarisation. Correlations were identified in type 1 patients between disease duration and nerve excitability parameters, including the relative refractory period (r = -0.533, p < 0.05). In contrast, only minor non-specific changes were noted in the type 2 group.
  
  
  CONCLUSIONS
  This study provides clear evidence of altered axonal function in patients with type 1 diabetes in the absence of clinical neuropathy. These findings suggest that altered axonal membrane potential may precede neuropathy onset in type 1 diabetes and as such may indicate a window of opportunity to intervene and potentially reverse axonal membrane dysfunction before the development of irreversible neuropathy.
authors.affiliation: Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Ria
authors.initials: R
authors.lastname: Arnold
authors.forename: Natalie
authors.initials: N
authors.lastname: Kwai
authors.forename: Cindy S-Y
authors.initials: CS
authors.lastname: Lin
authors.forename: Ann M
authors.initials: AM
authors.lastname: Poynten
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000368:Aged; D001369:Axons / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*