Increased inflammatory effect of electronegative LDL and decreased protection by HDL in type 2 diabetic patients

Abstract Background and aims Type 2 diabetic patients have an increased proportion of electronegative low-density lipoprotein (LDL(−)), an inflammatory LDL subfraction present in blood, and dysfunctional high-density lipoprotein (HDL). We aimed at examining the inflammatory effect of LDL(−) on monocytes and the counteracting effect of HDL in the context of type 2 diabetes. Methods This was a cross-sectional study in which the population comprised 3 groups (n = 12 in each group): type 2 diabetic patients with good glycaemic control (GC-T2DM patients), type 2 diabetic patients with poor glycaemic control (PC-T2DM), and a control group. Total LDL, HDL, and monocytes were isolated from plasma of these subjects. LDL(−) was isolated from total LDL by anion-exchange chromatography. LDL(−) from the three groups of subjects was added to monocytes in the presence or absence of HDL, and cytokines released by monocytes were quantified by ELISA. Results LDL(−) proportion and plasma inflammatory markers were increased in PC-T2DM patients. LDL(−) from PC-T2DM patients induced the highest IL1β, IL6, and IL10 release in monocytes compared to LDL(−) from GC-T2DM and healthy subjects, and presented the highest content of non-esterified fatty acids (NEFA). In turn, HDL from PC-T2DM patients showed the lowest ability to inhibit LDL(−)-induced cytokine release in parallel to an impaired ability to decrease NEFA content in LDL(−). Conclusions Our findings show an imbalance in the pro- and anti-inflammatory effects of lipoproteins from T2DM patients, particularly in PC-T2DM.