**1. Introduction**

Endothelial dysfunction is one of the major causes for vascular complications, accompanied by oxidative stress and inflammation. In diabetic and obesity/insulin resistance states, the endothelial dysfunction is incremented promoting the development and progression of vascular diseases [1].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Endothelial dysfunction involves reduced endothelium-dependent vasodilatation and a prothrombotic, pro-inflammatory and oxidant milieu [2]. The endothelial nitric oxide (NO) synthase (eNOS), renin-angiotensin-aldosterone and kallikrein-kinin response systems all fail to maintain normal vascular homeostasis in conditions of hyperglycemia, reactive oxidative species (ROS), free fatty acid (FFA) stress, and pro-inflammatory signaling [3, 4].

**2.2. Inflammation**

A state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes. The inflammation can be monitored by inflammatory markers such as high sensitivity C-reactive protein (hsCRP) and the inflammatory score derived from the pro-inflammatory plasma cytokines, interleukin (IL)-6, tumor necrosis factor α (TNFα), osteopontin, fractalkine, chemokine (C-C motif) ligand 2 (CCL2) and anti-inflammatory adiponectin, that inversely relate to insulin sensitivity (**Table 1**). The inflammatory score independently predicted fasting plasma glucose and insulin resistance in type 2 diabetic patients with high sensibility and specificity [9–12]. Moreover, other inflammatory biomarkers [i.e., growth differentiation factor-15 (GDF15), myeloid-related protein 8/14, pentraxin 3, lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1)] have been considered surrogate markers of cardiovascular disease and atherosclerosis in type 2 diabetes patients [13–16].

Endothelial Dysfunction in Type 2 Diabetes: Targeting Inflammation

http://dx.doi.org/10.5772/intechopen.76994

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GDF15 is a member of the transforming growth factor beta family, secreted from cells such as adipocytes and myocytes in response to cellular ischemia and oxidative stress both present in diabetes. GDF15 is a marker of oxidative stress and inflammation and provides independent

**Figure 1.** Major functions of endothelial cells: regulation of vascular tone, control of VSMC proliferation, inflammation, permeability, angiogenesis, metabolism and hemostasis. Ang II, angiotensin II; CAMs, cell adhesion molecules; CCL; chemokine (C-C motif) ligand; EC, endothelial cell; EDHF, endothelium derived hyperbolizing factor; EGF,

sulfate proteoglycans; ICAM, intercellular adhesion molecule; NO, nitric oxide; PAF, platelet-activating factor; PAI-1,

ROS, reactive oxygen species; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TGF-β, transforming growth

; thromboxane A2

vascular endothelial growth factor; VSMC, vascular smooth muscle cells; vWF, von Willebrand factor.

S; hydrogen sulfide; HSPG, heparan

; PGI2

, prostacyclin;

, prostaglandin H2

; VCAM, vascular cell adhesion molecule; VEGF,

epidermal growth factor; ET1, endothelin-1; FGF, fibroblast growth factor; H2

Plasminogen activator inhibitor-1; PDGF, platelet-derived growth factor; PGH2

factor-β; t-PA, tissue plasminogen activator; TXA2

prognostic information on cardiovascular events [17].

The aim of this review is to address the role of inflammation and its mechanisms in endothelial dysfunction associated with diabetes, describing the impact of these conditions on vascular function. We searched PubMed and Google Scholar primarily for original research articles published up to 2017 that were focused on the pathophysiology of endothelial dysfunction associated with type 2 diabetes. The main search terms used were "type 2 diabetes," "inflammation and endothelial dysfunction," "insulin resistance," and "therapies". We identified primarily full-text manuscripts written in English. We also searched Clinicaltrials.gov for information on ongoing clinical trials in endothelial dysfunction associated with type 2 diabetes.
