OBJECTIVE: To investigate the effects of hyperglycemia on axonal excitability in human diabetics. Diabetic nerve dysfunction is partly associated with the altered polyol pathway and Na+-K+ ATPase activity, probably resulting in a decrease in the trans-axonal Na+ gradient and reduced nodal Na+ currents. METHODS: Threshold tracking was used to measure the relative refractory periods (RPs) of median motor axons in 58 diabetic patients, 45 normal subjects, and 12 patients with non-diabetic axonal neuropathy. In diabetic patients, the relationship of RPs with hemoglobin A1c (HbA1c) levels was analyzed. RESULTS: The mean RP was similar for diabetics and normal controls as a group, but was longer in patients with non-diabetic neuropathy than in normal controls (P=0.02). Diabetic patients with good glycemic control (HbA1c levels <7%) had longer RPs than patients with poorer glycemic control and normal controls (P=0.01). RP was longest at the HbA1c level of 6%, gradually decreasing and reaching a plateau at the HbA1c level of 8-9%. CONCLUSIONS: Hyperglycemia shortens RPs, possibly because metabolic abnormalities lead to reduced nodal Na+ currents, and thereby to a lower inactivation of Na+ channels when generating an action potential. SIGNIFICANCE: RP measurements could provide new insights into the ionic pathophysiology of human diabetic neuropathy.
OBJECTIVE: To investigate the effects of hyperglycemia on axonal excitability in humandiabetics. Diabetic nerve dysfunction is partly associated with the altered polyol pathway and Na+-K+ ATPase activity, probably resulting in a decrease in the trans-axonal Na+ gradient and reduced nodal Na+ currents. METHODS: Threshold tracking was used to measure the relative refractory periods (RPs) of median motor axons in 58 diabeticpatients, 45 normal subjects, and 12 patients with non-diabetic axonal neuropathy. In diabeticpatients, the relationship of RPs with hemoglobin A1c (HbA1c) levels was analyzed. RESULTS: The mean RP was similar for diabetics and normal controls as a group, but was longer in patients with non-diabetic neuropathy than in normal controls (P=0.02). Diabeticpatients with good glycemic control (HbA1c levels <7%) had longer RPs than patients with poorer glycemic control and normal controls (P=0.01). RP was longest at the HbA1c level of 6%, gradually decreasing and reaching a plateau at the HbA1c level of 8-9%. CONCLUSIONS:Hyperglycemia shortens RPs, possibly because metabolic abnormalities lead to reduced nodal Na+ currents, and thereby to a lower inactivation of Na+ channels when generating an action potential. SIGNIFICANCE: RP measurements could provide new insights into the ionic pathophysiology of humandiabetic neuropathy.
Authors: Jorge R Miranda-Massari; José R Rodríguez-Gómez; Michael J González; Carlos Cidre; Jorge Duconge; Heriberto Marín; Kazuko Grace; Howard L McLeod Journal: Int J Diabetes Res Date: 2016
Authors: Natalie C G Kwai; Ria Arnold; Chathupa Wickremaarachchi; Cindy S-Y Lin; Ann M Poynten; Matthew C Kiernan; Arun V Krishnan Journal: Diabetes Care Date: 2013-02-12 Impact factor: 19.112