Pathogenesis and Treatment of Diabetic Peripheral Neuropathy

Abstract

Diabetic neuropathy is the most common chronic complication of both type 1 and type 2 diabetes mellitus. Diabetic peripheral neuropathy (DPN), especially, distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Pathogenesis of the DPN is associated with glycemic dysregulation, which results in activation of polyol, aldose reductase, hexosamine, and protein kinase C pathway and leads to downstream inflammation, generation of reactive oxygen species, and decreased blood flow to peripheral nerves. Furthermore, metabolic syndrome components such as obesity, insulin resistance, and dyslipidemia result in mitochondrial dysfunction and endoplasmic reticulum stress, eventually contributing to axonal failure and apoptosis of nerve cells. Despite its high prevalence, DPN is still underdiagnosed. Among DPN symptoms, neuropathic pain is challenging to manage, resulting in increased risk of associated problems such as sleep disturbance, reduced quality of life, and socioeconomic consequences. Therefore, early diagnosis and active multidisciplinary treatment of DPN is needed.