Hyperglycemia alters refractory periods in human diabetic neuropathy.
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.


CONCLUSIONS
RP measurements could provide new insights into the ionic pathophysiology of human diabetic neuropathy.
Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. sonoko.m@mb.infoweb.ne.jp
Sonoko
S
Misawa
Satoshi
S
Kuwabara
Kazue
K
Ogawara
Yukiko
Y
Kitano
Kazuo
K
Yagui
Takamichi
T
Hattori
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons; D016022:Case-Control Studies; D003929:Diabetic Neuropathies / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000503:physiopathology; D012032:Refractory Period, Electrophysiological; D013997:Time Factors
D006442:Glycated Hemoglobin