Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease

Abstract

Metabolic syndrome (MetS) is considered a metabolic disorder that has been steadily increasing globally and seems to parallel the increasing prevalence of obesity. It consists of a cluster of risk factors which traditionally includes obesity and hyperlipidemia, hyperinsulinemia, hypertension, and hyperglycemia. These four core risk factors are associated with insulin resistance (IR) and, importantly, the MetS is known to increase the risk for developing cerebrocardiovascular disease and type 2 diabetes mellitus. The MetS had its early origins in IR and syndrome X. It has undergone numerous name changes, with additional risk factors and variables being added over the years; however, it has remained as the MetS worldwide for the past three decades. This overview continues to add novel insights to the MetS and suggests that leptin resistance with hyperleptinemia, aberrant mitochondrial stress and reactive oxygen species (ROS), impaired folate-mediated one-carbon metabolism with hyperhomocysteinemia, vascular stiffening, microalbuminuria, and visceral adipose tissues extracellular vesicle exosomes be added to the list of associated variables. Notably, the role of a dysfunctional and activated endothelium and deficient nitric oxide bioavailability along with a dysfunctional and attenuated endothelial glycocalyx, vascular inflammation, systemic metainflammation, and the important role of ROS and reactive species interactome are discussed. With new insights and knowledge regarding the MetS comes the possibility of new findings through further research.

Fatness but not Fitness Linked to BrainAge: Longitudinal Changes in Brain Aging during an Exercise Intervention

“…For instance, VAT has been linked to reduced immunity secondary to increased levels of inflammation (38) and to increased oxidative stress resulting from upregulated cytokine activation (39). However, potentially most compelling given the observed links between brain insulin resistance and decreased cognitive function and brain structure (32) is the fact that increased VAT contributes to decreased insulin sensitivity systemwide (40). Although these data do not confirm a causal relationship between VAT and insulin (in)sensitivity in the brain, and there is a possibility of shared etiology that affects both independently, they do suggest the possibility of a causal pathway in which increased insulin resistance and visceral adiposity are linked both to each other and to structural brain health.…”

Why Are Perivascular Spaces Important?

“…Because EPVS can now be visualized and identified by MRI, they are currently known to be clinically relevant. In addition to visualizing PVS and EPVS by MRI, PVS and EPVS may also be identified by transmission electron micrographic (TEM) studies ( Figure 4 ) [ 6 ].…”

A Systematic Review and Meta-Analysis of Automated Methods for Quantifying Enlarged Perivascular Spaces in the Brain

“…The relevance of PVS has become increasingly evident in areas not studied before such as in relation to the occlusion of sinonasal cavities (Sáenz de Villaverde Cortabarría et al, 2023; Valdés Hernández et al, 2023), in patients with the metabolic syndrome (Hayden, 2023), or in patients with amyotrophic lateral sclerosis (Schreiber et al, 2023), and, with it, the efforts in improving the accuracy of the currently accepted as state-of-the-art computational methods to assess them in the presence of confounding pathology such as white matter hyperintensities (WMH) or lacunes.…”