Neutrophils and their role in the aetiopathogenesis of type 1 and type 2 diabetes

Abstract

Multiple and complex aetiological processes underlie diabetes mellitus, which invariably result in the development of hyperglycaemia. Although there are two prevalent distinct forms of the disease, that is, type 1 and type 2 diabetes, accumulating evidence indicates that these syndromes share more aetiopathological mechanisms than originally thought. This compels a rethinking of the approaches to prevent and treat the different manifestations of what eventually becomes a hyperglycaemic state. This review aims to address the involvement of neutrophils, the most abundant type of granulocytes involved in the initiation of the acute phase of inflammation, in the aetiopathogenesis of diabetes mellitus, with a focus on type 1 and type 2 diabetes. We review the evidence that neutrophils are the first leucocytes to react to and accumulate inside target tissues of diabetes, such as the pancreas and insulin-sensitive tissues. We then review available data on the role of neutrophils and their functional alteration, with a focus on NETosis, in the progression towards clinical disease. Finally, we review potential approaches as secondary and adjunctive treatments to limit neutrophil-mediated damage in the prevention of the progression of subclinical disease to clinical hyperglycaemia.

A Plasma miR-193b-365 Signature Combined With Age and Glycemic Status Predicts Response to Lactococcus lactis–Based Antigen-Specific Immunotherapy in New-Onset Type 1 Diabetes

“…( 48 ), and Giovenzana et al. ( 49 )). Some studies described diminished peripheral-blood neutrophil counts coinciding with increased migration of these cells in the pancreas, in at-risk participants and those with type 1 diabetes ( 50 , 51 ), whereas other reports revealed increased, circulating platelet–neutrophil aggregates implicated in innate immune activation and migration, in at-risk children and children with new-onset type 1 diabetes ( 52 ).…”

Neutrophils for Revascularization Require Activation of CCR6 and CCL20 by TNFα

“…We additionally evaluated potential off-target effects on pancreatic tissue by our approach, since both elevated numbers of neutrophils and administration of statins have been associated with an accelerated progression of diabetes 32,33 (Figure S19). Compared with untreated and nonligated WT mice, we observed morphological alterations in the pancreas of diabetic mice, reflecting the destruction of insulin-producing β cells following treatment with streptozotocin (Figure S19A).…”

Exploring the Correlation Between the Systemic Immune Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Type 2 Diabetic Retinopathy

“…Research, such as that conducted by Giovenzana et al highlights significantly elevated neutrophil levels in type 2 diabetes patients compared to healthy subjects. 20 Neutrophils can regulate immunity through a variety of mechanisms. In recent years, extra neutrophil traps (NETs) have emerged as a new immune defense mechanism and an important regulator of diabetes and its complications.…”