Association of Plasma Proteins at Multiple Stages of Glycation and Antioxidant Status with Erythrocyte Oxidative Stress in Patients with Type 2 Diabetes

Abstract

This study examines the individual stages of plasma protein glycation, antioxidant status and their association with erythrocyte oxidative stress in patients with type 2 diabetes mellitus (T2DM). Study was carried out on blood from 70 patients with T2DM and 40 healthy age-and gender-matched volunteers. Biomarkers of plasma protein glycation (fructosamine, protein carbonyls, advanced glycation end products [AGEs], amyloid), antioxidant status (thiols, total antioxidant capacity and erythrocyte oxidative parameters), osmotic fragility, lipid peroxidation (LPO), reduced glutathione (GSH) and catalase were determined. Plasma glycation markers were higher in T2DM patients than in healthy volunteers: fructosamine 578 vs. 525 μmol/mL; carbonyl 21.23 vs. 18.84 nmol/mg protein (P<0.01); AGEs 213.94 vs. 178.27 AU/mg protein (P< 0. 05); and amyloid 0.53 vs. 0.40 A530 nm (P<0.01). Plasma antioxidant status was significantly reduced in patients with diabetes compared to the healthy volunteers, with lower plasma protein thiols (1.16 vs. 1.36 nmol/mg protein; P<0.01) and total antioxidant capacity (26 vs. 34 μmol; P<0.01). Erythrocytes from the patient group were found to show greater oxidative damage, with elevated numbers of fragile cells and increased LPO, and reduced GSH level. Among the glycation markers, positive correlations were evident between fructosamine and amyloid (r=0.350, P<0.001) and AGEs and amyloid (r=0.070). Plasma glycation markers showed negative correlation with plasma antioxidant status while positive correlation was demonstrated between erythrocytes fragility and AGEs and amyloid. Erythrocyte LPO levels correlated positively with amyloid. These data suggest that increased levels of multiple plasma protein glycation products in T2DM patients play a key role in reduced plasma antioxidant status and amplified erythrocyte oxidative damage.