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

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.

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.

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).

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.

Measurements of tau(SD) could provide a new insight into changes in ionic conductance in human diabetic nerves.