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[DOI] [PMC free article] [PubMed] [Google Scholar] Reynolds IJ, Hastings TG

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3 Definition, pathophysiology, risk factors of DPN 3.1 Definition DPN is considered a symmetrical, length-dependent sensorimotor polyneuropathy attributable to metabolic and microvascular alterations due to chronic hyperglycemia exposure (diabetes) and cardiovascular risk covariates ( DPN progresses gradually with increasing duration of diabetes and in relation to glycemic control in both T1D and T2D ( 3.2 Pathophysiology Although the exact pathophysiology of DPN remains unknown, the role of various signaling cascades has been proposed such as advanced glycation end-product (AGE) pathway, polyol pathway, protein kinase C (PKC) pathway, hexosamine pathway and poly (ADP ribose) polymerase (PARP) pathway ( Nonetheless, chronic hyperglycemia is the main underlying cause of DPN, which leads to damage at the vascular level and the free passage of glucose to neurons and Schwann cells, resulting in an imbalance between nerve damage and nerve fiber repair ( The causes of DPN are thought to be a multi-factorial metabolic process that increasingly deteriorates tissues