Diabetic Autonomic Neuropathy: Pathogenesis to Pharmacological Management

Abstract

Diabetic autonomic neuropathy is a debilitating complication of diabetes which can cause heart disease, gastrointestinal symptoms, genitourinary disorders and metabolic diseases. Hyperglycemia induces glucose flux through the polyol pathway; excess/inappropriate activation of Protein Kinase C (PKC) isoforms; accumulation of Advanced Glycation End products (AGE’s) and these pathways are associated with metabolic and/or redox state of the cell. Activation of these metabolic pathways leads to oxidative stress which is a mediator of hyperglycemia induced cell injury and is a unifying theme for all mechanisms of diabetic autonomic neuropathy. Glycemic control can slow the onset of diabetic autonomic neuropathy and may reverse it. Pharmacologic and non-pharmacologic therapies are available to treat various symptoms of diabetic autonomic neuropathy. This review focuses on the pathology, animal models and therapeutic approaches available for the management of diabetic autonomic neuropathy.