Unraveling Leukocyte Dysfunction in Type 2 Diabetes: The Mechanistic Link Between Hyperglycemia, Chronic Systemic Inflammation, and Impaired Host

Abstract

The risks of infection are significantly increased in type 2 diabetes mellitus (T2D) by mechanisms of immune dysregulation. Leukocytes are chronically exposed to excess production of ROS and AGE due to hyperglycemia.This hyper-glycemia induces the over-production of ROS and AGEs in leukocytes. This state of chronic, low-grade systemic inflammation is caused by high levels of pro-inflammatory cytokines like IL-6 and TNF-α.As a result, important functions of leukocytes, such as the ability to chemotaxis, phagocytose, kill intracellular pathogens and undergo NETosis are all severely impaired. Other signaling pathways are also dysregulated leading to exacerbated immune dysfunction and inefficient recruitment of immune cells to sites of infection. These metabolic and inflammatory changes render the body vulnerable to infections and slow down wound healing. These specific biochemical cascades are targets for therapeutic interventions to restore host immune competence in T2D patients.