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

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 IL1 beta, 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. (C) 2017 Elsevier B.V. All rights reserved.