The Role of Inflammation in the Pathogenesis of Diabetic Peripheral Neuropathy: New Lessons from Experimental Studies and Clinical Implications

Abstract

Diabetic peripheral neuropathy (DPN) is one of the most frequent complications of diabetes mellitus (DM). Its pathogenesis is still not entirely clear. Inflammation is increasingly being appreciated as a key factor in its development and progression. The aim of this review was to outline current evidence from experimental research on the role of inflammation in the pathogenesis of DPN and to suggest emerging clinical implications. Beyond commonly assessed interleukins, chemokines and tumour necrosis factor alpha (TNFα), several novel underlying mechanisms and potential therapeutic targets have been unravelled. Pathogenesis is also influenced by dietary patterns, such as iron supplementation. Furthermore, the impact of the inflammasome nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein 3 (NLPR3) is gaining importance. The same holds true for inflammatory pathways, such as the Toll-like receptor (TLR)-associated pathways or the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. SIRTuins are also of importance. DPN is associated with changes in macrophage polarisation. In addition, several metalloproteinases are emerging as contributors, although data is still limited. Finally, miRNAs (e.g. miR146a) are strongly linked with DPN by acting in several inflammatory pathways. However, we still need confirmation of preliminary research findings. It is hoped that new knowledge will lead to new therapeutic approaches, including stem cell-based or exosome-based therapies.

Keywords: Diabetes mellitus; Diabetic peripheral neuropathy; Distal symmetric polyneuropathy; Inflammation; Type 1 diabetes mellitus; Type 2 diabetes mellitus.