Pathogenesis of diabetic neuropathy

TLDR

The study examined lumbosacral trunk, posterior tibial, and sural nerves from diabetic and nondiabetic autopsies using thin epoxy sections and teased fiber preparations. Diabetic nerves showed focal fascicular lesions with reduced myelinated axon density, especially in the posterior tibial nerve and lumbosacral trunk, causing ischemic damage and a proximal–distal loss of fibers that correlated with lesion density, while similar lesions appeared in vasculitic nondiabetic nerves, indicating that microangiopathy‑related focal lesions contribute to diabetic neuropathy.

Abstract

Abstract Samples of lumbosacral trunk, posterior tibial nerve, and sural nerve obtained at autopsy from diabetic and nondiabetic patients without mononeuropathy multiplex were evaluated using 1‐μ‐thick epoxy sections and teased nerve fiber preparations. Focal fascicular lesions characterized by reduced density of myelinated axons within fascicles were found predominantly in the specimens from diabetics, mainly in the posterior tibial nerve and lumbosacral trunk. In severe examples, the perineurium and even surrounding epineurium were damaged, stamping the lesions as ischemic. In addition, identical lesions were found in biopsies of nerves of nondiabetics with vascultis. Density of myelinated fibers at the three sites demonstrated a proximal–distal graded loss that was significantly greater in the diabetic samples. The loss from the lumbosacral trunk to the posterior tibial nerve was correlated with the density of focal lesions in the lumbosacral trunk in the diabetic ( p = 0.025), indicating that distal fiber loss was partly due to the focal lesions. Teased nerve fiber abnormalities were common only in sural nerves of diabetics, suggesting that they are secondary. We conclude that beyond the possible metabolic abnormalities involved in the genesis of diabetic polyneuropathy, focal fascicular lesions, likely due to diabetic microangiopathy, are also important in the development of diabetic neuropathy.