Is glycation of low density lipoproteins in patients with Type 2 diabetes mellitus a LDL pre-oxidative condition?

Aims The study aimed to evaluate whether low density lipoprotein (LDL) in diabetic patients is more glycated and susceptible to oxidation than in nondiabetic subjects and investigated the hypothesis that LDL glycation is associated with an increased plasma concentration of LDL- (a circulating electronegatively charged LDL), proposed as an index of in vivo oxidation. Methods LDL glycation was measured by a competitive enzyme immunoadsorbent assay, using a monoclonal antibody against glycated apoB in 24 Type 2 diabetic patients and 12 healthy controls. LDL- was separated by ion-exchange HPLC in LDL samples obtained after sequential preparative ultracentrifugation (density range 1.019-1.063). In vitro LDL susceptibility to oxidation was evaluated by following the kinetics of conjugated diene formation and by measuring the lag-phase time in the presence of copper (Cu2+)ions. Results The percentages of glycated apoB (3.33 +/- 2.54% vs. 1.24 +/- 0.71%) and of LDL- (3.88 +/- 1.49% vs. 2.34 +/- 1.03%) in total LDL were significantly higher in diabetic patients (P<0.01 for both). LDL- was positively correlated with glycated apoB (r = 0.68, P < 0.001). LDL isolated from Type 2 diabetic patients showed a significant decrease (P < 0.001) in the resistance to oxidative stress, as indicated by the shorter lag-phase time (91+/-12.6 vs. 120 +/- 24.5 min). The lag-phase time was inversely correlated with glycated apoB (r = -0.65, P < 0.001) and LDL- concentrations (r = -0.69, P < 0.001). Conclusions In this population of Type 2 diabetic patients, LDL were more glycated, more susceptible to in vitro oxidation and had a higher percentage of electronegative LDL. The glycation of apoB is proposed to be associated with a significative increase of in vivo and in vitro LDL oxidation.