Diabetes mellitus (DM) is a pandemics that affects more than 170 million people worldwide, associated with increased mortality and morbidity due to coronary artery disease (CAD). In type 1 (T1) DM, the main pathogenic mechanism seems to be the destruction of pancreatic β-cells mediated by autoreactive T-cells resulting in chronic insulitis, while in type 2 (T2) DM primary insulin resistance, rather than defective insulin production due to β-cell destruction, seems to be the triggering alteration. In our study, we investigated the role of systemic inflammation and T-cell subsets in T1- and T2DM and the possible mechanisms underlying the increased cardiovascular risk associated with these diseases. 1. Introduction Diabetes mellitus (DM) is a pandemics that affects more than 170 million people worldwide [1, 2], associated with increased mortality and morbidity due to coronary artery disease (CAD) [3, 4]. Patients with DM have 2- to 4-fold increase in risk of CAD and up to 3-fold increase in mortality and carry the same level of risk for subsequent acute coronary events as nondiabetic patients with previous myocardial infarction (MI). DM also worsens early and late outcomes in acute coronary syndromes (ACS) [5, 6]. Indeed, DM is a prothrombotic condition, associated with inflammation, altered innate immunity, and impaired endothelial function [7, 8]. However, the mechanisms responsible for the higher cardiovascular risk that accompanies DM are multiple and still largely unknown. In type 1 (T1) DM, the main pathogenic mechanism seems to be the destruction of pancreatic -cells mediated by autoreactive T-cells resulting in chronic insulitis. Thus, the chronic inflammation of pancreatic islets plays a pivotal role in the development of the disease [9]. In type 2 (T2) DM, primary insulin resistance, rather than defective insulin production due to -cells destruction, seems to be the triggering alteration. Insulin resistance leads to a perturbation in the lipid homeostasis, cytokines, and adipokines production, resulting in increased systemic inflammation, with higher levels of inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)- [7, 10–16]. Inflammation and immunity play also a key role in the pathogenesis of atherosclerosis and its complications. Immune responses are a cornerstone in the mechanisms of endothelial activation, plaque development, and rupture, as demonstrated by the correlations between levels of inflammatory markers or certain lymphocyte population and the risk of occurrence of cardiovascular
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