Metabolic Mechanisms in Diabetic Neuropathy

Abstract

According to the American Diabetes Association, in 2015, 9.4% of the United States population had diabetes and about 50% of these patients will or already have developed peripheral neuropathy. Furthermore, peripheral neuropathy is detectable in about 30% of subjects with pre-diabetes and impaired glucose tolerance. The only treatment recognized for diabetic peripheral neuropathy is glycemic control, which slows progression in patients with type 1 diabetes but is less effective in subjects with type 2 diabetes. With the occurrence of obesity and type 2 diabetes at epidemic levels there is a critical need of a treatment. Diabetic peripheral neuropathy has a complex etiology with at least six major pathways involved in its development: metabolic, vascular, immunologic, neurohormonal growth factor deficiency, genetic, and extracellular matrix remodeling. In light of this complicated etiology any effective treatment for diabetic peripheral neuropathy will likely require a combination of lifestyle and therapeutic interventions. However, before an effective treatment strategy can be developed a more comprehensive understanding of the factors contributing to neurovascular and neural dysfunction in diabetes is needed. This article will address some of the major mechanisms including aldose reductase pathway, non-enzymatic glycation, hexosamine and protein kinase C pathways, oxidative and nitrosative stress, inflammatory stress, and proteases thought to contribute to the development and progression of diabetic peripheral neuropathy.