Neutrophil extracellular traps (NETosis) as a factor contributing to the development and progression of diabetes mellitus and its microvascular complications

NETosis, a new form of cell death, has attracted close attention of researchers in recent years due to its dual eff ect on the pathological process. Being initially a defense reaction of the innate immune defenсe aimed at trapping and neutralizing pathogens (bacteria, viruses and fungi) that have invaded the body, NETosis, in case of excessive activation, has an opposite eff ect. It can contribute to the progression of the disease, causing autoimmunization, damage to surrounding tissue, or the occurrence of atherothrombotic events. This review presents data dealing with the formation of extracellular traps of neutrophils, called NETs. NETosis plays an important role in the pathogenesis of diabetes mellitus (DM) and its microvascular complications. For example, in type 1 DM, β-cell death promotes sequestration of neutrophils into the pancreas and is clearly correlated with increased NETosis. In patients with type 2 DM, the release is also signifi cantly increased. High levels of dsDNA, a marker of NETosis, are correlated with the development of cardiovascular disease and DM caused kidney disease, which is also consistent with the contributing role of NETosis in the pathogenesis of diabetic complications such as impaired wound healing and diabetic retinitis. The mechanisms linking NETosis with high glucose levels are not clearly understood, as NETosis is also increased in diabetic patients strictly controlling glucose levels. One can only assume that NETosis is not a consequence of impaired glycemic control. On the contrary, it causes hyperglycemia, which further increases the initially high level of NETosis in patients with DM.