Impact of the LDL subfraction phenotype on Lp-PLA2 distribution, LDL modification and HDL composition in type 2 diabetes

Abstract

BackgroundQualitative alterations of lipoproteins underlie the high incidence of atherosclerosis in diabetes. The objective of this study was to assess the impact of low-density lipoprotein (LDL) subfraction phenotype on the qualitative characteristics of LDL and high-density lipoprotein (HDL) in patients with type 2 diabetes.MethodsOne hundred twenty two patients with type 2 diabetes in poor glycemic control and 54 healthy subjects were included in the study. Patients were classified according to their LDL subfraction phenotype. Seventy-seven patients presented phenotype A whereas 45 had phenotype B. All control subjects showed phenotype A. Several forms of modified LDL, HDL composition and the activity and distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) were analyzed.ResultsOxidized LDL, glycated LDL and electronegative LDL were increased in both groups of patients compared with the control group. Patients with phenotype B had increased oxidized LDL and glycated LDL concentration than patients with phenotype A. HDL composition was abnormal in patients with diabetes, being these abnormalities more marked in patients with phenotype B. Total Lp-PLA2 activity was higher in phenotype B than in phenotype A or in control subjects. The distribution of Lp-PLA2 between HDL and apoB-containing lipoproteins differed in patients with phenotype A and phenotype B, with higher activity associated to apoB-containing lipoproteins in the latter.ConclusionsThe presence of LDL subfraction phenotype B is associated with increased oxidized LDL, glycated LDL and Lp-PLA2 activity associated to apoB-containing lipoproteins, as well as with abnormal HDL composition.

Relationship between plasma phospholipase A2 concentrations and lipoprotein subfractions in patients with stable coronary artery disease

“…Gazi et al found that plasma Lp-PLA 2 activity was a marker of sdLDL due to the preferential distribution of Lp-PLA 2 in the sdLDL subfraction in patients with dyslipidemia [15]. A recent study demonstrated that the presence of LDL subfraction phenotype B (the predominance of sdLDL) was associated with an increased Lp-PLA 2 activity in patients with type 2 diabetes as well as with abnormal HDL composition [16]. Although both dyslipidemia and diabetes reflected high risk of cardiovascular disease, the pathophysiology of CAD was a more complicated process.…”

“…Hence, understanding the relationship between lipoprotein subfractions and Lp-PLA 2 may provide more evidence regarding the potential risk of Lp-PLA 2 for CAD. Previous data have reported the association between plasma Lp-PLA 2 activity and small dense LDL (sdLDL) in patients with dyslipidemia [15] or type 2 diabetes [16]. However, to the extent of our knowledge, the relationship between lipoprotein subfractions and Lp-PLA 2 has not been revealed in the status of CAD.…”

Effect of intensive insulin treatment on plasma levels of lipoprotein-associated phospholipase A2 and secretory phospholipase A2 in patients with newly diagnosed type 2 diabetes

“…According to this assumption, Lp-PLA 2 is anti-inflammatory when bound to HDL, but pro-inflammatory when bound to LDL [19]. Moreover, an increase in the binding between Lp-PLA 2 and LDL was observed in diabetic patients [20], which could support the pro-atherosclerotic role of Lp-PLA 2 in diabetes. However, studies on sPLA 2 in diabetic patients are lacking in the literature.…”

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

“…Because of this, some researcher raised a hypothesis that when linked to LDL, Lp-PLA 2 would be pro-atherogenic, whereas its action in the HDL particle would be anti--atherogenic (39). Other researchers observed that the greater the LDL/Lp-PLA 2 and HDL/Lp-PLA 2 ratio, the greater the levels of LDL-C, TG, glucose, insulin, and lower the levels of HDL-C in individuals with polycystic ovary syndrome (40).…”