Abstract
Type 2 diabetes mellitus and insulin resistance feature substantial modifications of the lipoprotein profile, including a higher proportion of smaller and denser low-density lipoprotein (LDL) particles. In addition, qualitative changes occur in the composition and structure of LDL, including changes in electrophoretic mobility, enrichment of LDL with triglycerides and ceramides, prolonged retention of modified LDL in plasma, increased uptake by macrophages, and the formation of foam cells. These modifications affect LDL functions and favor an increased risk of cardiovascular disease in diabetic individuals. In this review, we discuss the main findings regarding the structural and functional changes in LDL particles in diabetes pathophysiology and therapeutic strategies targeting LDL in patients with diabetes.
Highlights
The prevalence of type 2 diabetes mellitus (T2DM) has increased consistently worldwide for several decades, shifting the overall picture of cardiovascular disease (CVD) and its pathophysiological background
After the oxidation process is complete, Ox-low-density lipoproteins (LDL) lose their affinity for LDL receptors (LDLR) and bind to scavenger receptors (SRs) [18], such as class A1 scavenger receptor (SR-A1), CD36, lectin-like oxidized LDL receptor-1 (LOX-1), scavenger receptor expressed by endothelial cell-I (SREC), scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX), and CD68 [54]
A study showed that mice whose gene encoding the very-low-density lipoprotein (VLDL) receptor was invalidated and who were subjected to a fatty diet exhibited better tolerance to glucose and better sensitivity to insulin than wild mice subjected to the same diet [100], suggesting the possibility that VLDL-CER may play a role in modulating the insulin sensitivity of these animals
Summary
The prevalence of type 2 diabetes mellitus (T2DM) has increased consistently worldwide for several decades, shifting the overall picture of cardiovascular disease (CVD) and its pathophysiological background. Several other changes in the lipid profile have been reported, regarding LDL particles, which may influence the cardiovascular risk. An essential factor for the change in LDL phenotype in T2DM is a decline in insulin sensitivity [4]. Elevated Ox-LDL concentration is associated with an increased risk of incident diabetes due to its effects on β-cells [9] and with a higher risk of developing obesity and CVD [7]. This indicates a bidirectional association between Ox-LDL and T2DM. We discuss recent advances in the evidence of biological mechanisms that underlie LDL phenotype changes during T2DM pathology and their clinical and therapeutic implications
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