Bioenergetics in diabetic neuropathy: what we need to know

Abstract

Progress in developing treatments for diabetic neuropathy is slowed by our limited understanding of how disturbances in metabolic substrates- glucose and fatty acids- produce nerve injury. In this review, we present the current oxidative stress hypothesis and experimental data that support it. We identify weaknesses in our understanding of diabetes-disordered metabolism in the neurovascular unit; i.e. in critical cell types of the microvascular endothelium, peripheral sensory neurons, and supporting Schwann cells. Greater understanding of peripheral nervous system bioenergetics may provide insight into new drug therapies or improvements in dietary interventions in diabetes or even pre-diabetes.

Mitotoxicity in distal symmetrical sensory peripheral neuropathies

“…56 In addition, long-term exposure to excess glucose produces many effects that might impair mitochondrial function: hypoxia secondary to intraneural microvascular disease, accumulation of advanced glycation end products, exposure to elevated levels of methylglyoxal, polyol pathway hyperactivity, disruption of metabolic support from Schwann cells, and abnormal calcium homeostasis. 57–60 A full discussion of this complex picture is outside the scope of this Review, but we propose that a toxic effect of excess glucose on axonal mitochondria may be the fundamental precipitating factor, and that the other phenomena are contributors to an evolving pathological process.…”

Is type 2 diabetes mellitus associated with alterations in hearing? A systematic review and meta‐analysis

“…Oxidative stress has equally been implicated in the pathogenesis of diabetic neuropathy. 71 The presence of high glucose leads to the formation of free radicals through the defective functioning of the inner membrane of the mitochondria. This eventually results in excessive production of reactive oxygen species leading to neuronal cell death.…”

Exploring the association between diabetes mellitus and hearing loss: Genetic mutation, neuropathy and microangiopathy

“…In various literature reviews, there are some histopathological lesions, including neural destruction and microglial activation, in vestibulocochlear nerves due to hyperglycemia. These changes resulted from oxidative stress and dendritic damage, which ultimately resulted in an elevated level of reactive oxygen species (ROS) (Brownlee, 2001;Sonneville et al, 2012;Hinder et al, 2012;Helzner and Contrera, 2016). This evidence is a proof that there is a reduction of neurological transmission in affected neurons.…”