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 d iabetic patients is more glycated and susceptible to oxidation than in nond iabetic subjects and investigated the hypothesis that LDL glycation is asso ciated with an increased plasma concentration of LDL- (a circulating electr onegatively 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 diabe tic patients and 12 healthy controls. LDL- was separated by ion-exchange HP LC 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 me asuring 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 signifi cantly higher in diabetic patients (P<0.01 for both). LDL- was positively c orrelated 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 resist ance 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 wit h 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 g lycated, 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.