The Effect of Hyperglycemia on Nerve Conduction and Structure Is Age Dependent

The nerve conduction velocity (NCV) of nondiabetic male Wistar rats continues to increase until ∼ 26 weeks of age. Rats made hyperglycemic at 6 weeks of age manifest reduced NCV by 10 weeks of age and show morphological differences in the sciatic tibial nerve after 5 months of hyperglycemia when compared with age-matched controls. Fiber diameter, myelin width, and the number of large myelinated fibers were decreased in the tibial nerves of the hyperglycemic animals. Rats made hyperglycemic at 26 weeks of age had elevated glycosylated hemoglobin and sciatic nerve sorbitol levels but maintained normal NCVs and had little change in morphology after 7 months of hyperglycemia. Thus, animals with maturing peripheral nerve structure and function exposed to chronic hyperglycemia manifest greater pathological alterations than those that occur when more matured nerves are exposed to similarly elevated glucose concentrations for an even greater duration. We suggest that immature animal models commonly used to study diabetic peripheral neuropathy may not be appropriate for understanding a process that commonly develops in humans who become hyperglycemic after maturation of the peripheral nerves.