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 (tau(SD)), 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 tau(SD) with the state of glycemic control (hemoglobin A1c [HbA1c] levels) was analyzed.
Results: The mean tau(SD) 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 tau(SD) than the patient group with poor control (HbA1c>9%; P=0.04). The mean tau(SD) 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 tau(SD), when the HbA1c levels ranged from 5 to 9% (P=0.04).
Conclusions: In diabetic nerves, tau(SD) is generally longer than normal, but hyperglycemia is associated with paradoxically shortened tau(SD), 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 tau(SD) could provide a new insight into changes in ionic conductance in human diabetic nerves.