From lipids to glucose: Investigating the role of dyslipidemia in the risk of insulin resistance

Dyslipidemia is recognized as one of the most prevalent metabolic disorders and is frequently associated with other prevalent conditions, particularly diabetes mellitus. There appears to be a bidirectional connection between these two metabolic disorders. While considerable research has focused on how insulin resistance can lead to lipid abnormalities, the reverse relationship specifically, how dyslipidemia could assist in developing insulin resistance and diabetes mellitus has received relatively less attention. This review aims to comprehensively evaluate the mechanisms through which dyslipidemia can induce insulin resistance. Dyslipidemia is primarily classified into three main categories: hypercholesterolemia, hypertriglyceridemia, and low levels of HDL. These conditions may promote insulin resistance across multiple pathways, including the accumulation of lipid metabolites, dysfunction of pancreatic beta-cells, increased reactive oxygen species, endoplasmic reticulum stress and inflammation, endothelial dysfunction, alterations in adiponectin levels, changes in bile acid composition and concentration, and dysbiosis of gut microbiota. However, further investigation is required to fully elucidate the cellular and molecular mechanisms underlying the relationship between lipid disorders and insulin resistance. Emphasizing such research could facilitate the development of therapeutic strategies targeting both conditions simultaneously.