title: Progressive axonal dysfunction precedes development of neuropathy in type 2 diabetes.
abstract: To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA(1c) levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0-1 [n = 35]), grade 1 (TNS 2-8 [n = 42]), and grade 2/3 (TNS 9-24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA(1c) level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction.
authors.affiliation: Department of Neurology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Sung
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Liu
authors.forename: Natalie
authors.initials: N
authors.lastname: Kwai
authors.forename: Ria
authors.initials: R
authors.lastname: Arnold
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.forename: Cindy S-Y
authors.initials: CS
authors.lastname: Lin
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000368:Aged; D001369:Axons / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology; D011115:Polyneuropathies / Q000503:physiopathology*; D012720:Severity of Illness Index