How dysregulation of the immune system promotes diabetes mellitus and cardiovascular risk complications

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to insulin resistance or failure to produce insulin. Patients with DM develop microvascular complications that include chronic kidney disease and retinopathy, and macrovascular complications that mainly consist in an accelerated and more severe atherosclerosis compared to the general population, increasing the risk of cardiovascular (CV) events, such as stroke or myocardial infarction by 2- to 4-fold. DM is commonly associated with a low-grade chronic inflammation that is a known causal factor in its development and its complications. Moreover, it is now well-established that inflammation and immune cells play a major role in both atherosclerosis genesis and progression, as well as in CV event occurrence. In this review, after a brief presentation of DM physiopathology and its macrovascular complications, we will describe the immune system dysregulation present in patients with type 1 or type 2 diabetes and discuss its role in DM cardiovascular complications development. More specifically, we will review the metabolic changes and aberrant activation that occur in the immune cells driving the chronic inflammation through cytokine and chemokine secretion, thus promoting atherosclerosis onset and progression in a DM context. Finally, we will discuss how genetics and recent systemic approaches bring new insights into the mechanisms behind these inflammatory dysregulations and pave the way toward precision medicine.