The Role of Advanced Glycation End Products on Dyslipidemia

Abstract

Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs' production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.

Keywords: AGEs; atherogenic dyslipidemia; diabetes; glycated LDL; small, dense LDL.

Figure 1

Main pathways of AGEs formation and major detrimental effects. The figure was composed by using Servier Medical Art templates, licensed under a Creative Common Attribution 3.0 (https://smart.servier.com, accessed on 14 December 2022.).

Figure 2

The effects of glycated LDL particles on vascular cells. The figure was composed by using Servier Medical Art templates, licensed under a Creative Common Attribution 3.0 (https://smart.servier.com, accessed on 14 December 2022.).

Figure 3

Potential applications of AGEs and glycated LDL particles in the prevention and management of cardiometabolic diseases. The figure was composed by using Servier Medical Art templates, licensed under a Creative Common Attribution 3.0 (https://smart.servier.com, accessed on 14 December 2022.).