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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Perspective

Hyperglycemia-Induced Immune System Disorders in Diabetes Mellitus and the Concept of Hyperglycemic Memory of Innate Immune Cells: A Perspective

Author(s): Giuseppe Lisco, Vito Angelo Giagulli, Giovanni De Pergola, Edoardo Guastamacchia, Emilio Jirillo* and Vincenzo Triggiani

Volume 22, Issue 4, 2022

Published on: 20 January, 2022

Page: [367 - 370] Pages: 4

DOI: 10.2174/1871530321666210924124336

Abstract

A wealth of information suggests that hyperglycemia plays a paramount role in diabetes- related chronic complications. Notably, in Type 2 Diabetes Mellitus (T2DM), a persistent condition of hyperglycemia and altered insulin signaling seems to account for a status of chronic low-grade inflammation. This systemic inflammatory condition, in turn, depends on the profound impairment of the immune machinery, especially in some corporeal districts such as the adipose tissue, pancreatic islets, endothelia, and circulating leukocytes. Interestingly, poor glycemic control has been associated with cardiac autoimmunity in patients with Type 1 Diabetes (T1DM), and cardiac autoantibody positivity is associated with an increased risk of Cardiovascular Diseases (CVD) decades later. This condition also suggests a role for autoimmune mechanisms in CVD development in patients with T1DM, possibly through inflammatory pathways. Evidence has been provided for an elevated release of cytokines, such as interleukin (IL)-1 beta and IL-6, as well as chemokines (C-C motif Ligand 2 and IL-8). Of note, these mediators are responsible for abnormal leukocyte trafficking into many tissues, contributing to insulin resistance, reduced insulin secretion, and vascular complications. In fact, hyperglycemia in individuals with diabetes mellitus is associated with higher circulating E-selectin, soluble Cell Adhesion Molecule (sCAM)-1, and vascular CAM-1 compared to normoglycemic healthy volunteers. Therefore, patients with diabetes mellitus exhibit an exaggerated adhesion of leukocytes to endothelia, and this phenomenon is related to hyperglycemia. The increased production of advanced glycosylation end products or AGEs activates a further cascade of noxious events with a massive generation of Reactive Oxygen Radicals (ROS) and enhanced expression of CAMs.

Keywords: Diabetes mellitus, hyperglycemia, hyperglycemic memory, epigenetics, inflammation, trained immunity.

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