Peripheral nerve axonal dwindling with concomitant myelin sheath hypertrophy in experimentally induced diabetes

Axons of the peripheral nervous system (PNS) are reduced in caliber in response to the experimental diabetic state. The cause of this reduced axonal size is disputed. Various theories include (a) axonal dwindling, (b) inhibition of growth, and (c) shrinkage due to serum hyperosmolarity. This study was designed to directly address these conflicting theories and to provide additional information on the character of the peripheral neuropathy resulting from an experimentally induced diabetic state. Four weeks, 6 and 12 months after establishing a streptozotocin-induced diabetic condition in rats, a morphometric evaluation of randomly selected cross sections of myelinated nerve fibers in the common peroneal nerve was performed on diabetic and age and weight-matched control animals. A reduction in the cross-sectional area of axons with a concomitant increase in the width of myelin sheaths was detected following 6 months of exposure to the diabetic state. Axons in rats diabetic for 12 months showed smaller cross-sectional areas than those seen in rats diabetic for only 6 months; hence, a dwindling in axonal caliber had occurred during this period. These findings indicate the presence of an axonopathy, associated with a myelin sheath alteration in the common peroneal nerve of the chronically diabetic rat.