Paradigm of Insulin Resistance, Type 2 Diabetes, Obesity, Fatty Liver and Atherosclerosis in Metabolic Syndrome

Abstract

Insulin resistance is the most important characteristic of both metabolic syndrome (MetS) and type 2 diabetes mellitus (T2D). It is estimated that MetS has a prevalence of up to 35% in the general population, rising up to 72% in individuals with T2D. Furthermore, insulin resistance promotes lipotoxicity through an increased free fatty acids flux, leading to both liver and heart disorders. Thus, recent studies have proven the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with MetS and T2D. Interestingly, recent data incriminate the same mechanism for the development of metabolic cardiomyopathy, also known as cardiometabolic heart failure. The aim of this paper is to review the most important data regarding the association of T2D with the classic and the newer elements of the MetS, as well as to emphasize the molecular mechanisms that are accountable for this linkage and the possible therapeutic prospects that could influence these pathologies.