Strength-duration properties and glycemic control in human diabetic motor nerves

Objective To investigate the influences of hyperglycemia on axonal excitability in human diabetic nerves. Hyperglycemia results in decreased Na+–K+ pump function, presumably leading to intra-axonal Na+ accumulation and thereby, reduced Na+ currents. Methods The strength-duration time constant (τSD), which partly depends on persistent Na+ conductance active at the resting membrane potential, was measured in median motor axons of 79 diabetic patients. The relationship of τSD with the state of glycemic control (hemoglobin A1c [HbA1c] levels) was analyzed. Results The mean τSD was longer for diabetic patients than for normal controls, but the difference was not significant. Among diabetic patients, the subgroup of patients with good glycemic control (HbA1c<7%) had significantly longer τSD than the patient group with poor control (HbA1c>9%; P=0.04). The mean τSD was longest at the HbA1c level of 5–6%, gradually decreasing and reaching a plateau around the HbA1c level of 9%. There was an inverse relationship between HbA1c levels and τSD, when the HbA1c levels ranged from 5 to 9% (P=0.04). Conclusions In diabetic nerves, τSD is generally longer than normal, but hyperglycemia is associated with paradoxically shortened τSD, because of a decrease in axonal persistent Na+ conductance, possibly related to reduced membranous Na+ gradient, tissue acidosis, or other metabolic factors. Significance Measurements of τSD could provide a new insight into changes in ionic conductance in human diabetic nerves.