Impact of Glycemic Trajectory and Variability on Ischemic Stroke Prognosis and Exploration of Its Mechanisms: A Comprehensive Review.

Type 1 diabetes (T1D) is an autoimmune disorder characterised by auto-reactive immune cell-mediated death of pancreatic beta-cells [–]. The precise triggers that initiate pathogenesis of T1D remain unclear, with both genetic susceptibility and/or environmental triggers reported to prime autoimmune events in affected individuals [–]. Autoimmune events in T1D are characterised by islet infiltration by CD4 and CD8T-cells, in a process known as insulitis [–, ]. Cytotoxic CD4 and CD8T-cells secrete pro-inflammatory cytokines (e.g., TNFα, IFNγ) within the intra-islet environment [–], causing autoimmune-mediated death of beta-cells. Several issues surround current T1D treatments, including hypoglycaemia associated with exogenous insulin therapy and poor graft survival following islet transplantation [–]. Teplizumab, an anti-CD3 mAb which can delay development of T1D, was recently approved []. However, no drugs are currently available which can prevent or treat T1D. One candidate as a regulator of islet inflammation and T1D drug target is nicotinamide phosphoribosyltransferase (NAMPT). NAMPT is the rate-limiting enzyme in the NAD salvage pathway, where it catalyses conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD by NMN adenynyltransferase enzymes []. NAD+ metabolism regulates innate and adaptive immune response homeostasis []. However, accumulating evidence indicates that NAMPT activity, potentially mediated via enhanced NAD+ levels, can facilitate dysregulation of immunomodulatory processes and onset of inflammation.