Altered nerve excitability in subclinical/early diabetic neuropathy: Evidence for early neurovascular process in diabetes mellitus?

We sought to investigate the peripheral nerve excitability property of early diabetic neuropathy (DN) and provide a logical hypothesis regarding the pathophysiology of subclinical/early stage of DN. The automated nerve excitability test (NET) utilizing the threshold tracking technique (TTT) was performed to measure multiple excitability indices in 30 early DN and 30 normal subjects. Early DN was defined as N0 or N1 stage of Dyck's staging method. The protocols calculated strength-duration time constant (SDTC) from duration–charge curve, parameters of threshold electrotonus (TE) and current–threshold relationship (CTR) from sequential sub-threshold current, and recovery cycle (RC) from double supra-threshold stimulation. Each parameter of test was co-analyzed with clinical and laboratory data including age, sex, BMI, HgbA1c, lipid profile, and estimated glomerular filtration rate (eGFR). Compared to normal or N0 groups, N1 group had ‘fanning-in’ phenomenon in TE, increased refractory period, and decreased supernormality/subnormality. Linear regression showed that parameters associated with vascular factor were significantly related with STDC: absolute TG values were positively associated with STDC, whereas eGFR values were inversely related with STDC. Nerve excitability can be altered even in the early mild DN. The pattern of alteration suggests depolarizing nerve or nerve ischemia in pathophysiology of subclinical/early DN.