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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 (29)

In addition to hormones, various small molecules such as cytokine inhibitors including TNF inhibitors (infliximab, etanercept, ardamuzumab) and IL-6 receptor antagonists (toximab), T cell activation modulators, and abbasiprol are now utilized clinically to treat RA (101)

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