A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications

ObjectivesEnhanced formation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions has been linked to diabetes mellitus (DM) associated complications. We investigated the clinical relevance of estimating AGEs and their relationship with oxidative stress (OS) and paraoxonase (PON1) activity in type 2 DM (T2DM) in relation to development of vascular complications.Design and MethodsSerum AGEs along with PON1 activity, protein carbonyl (PCO), advanced oxidation protein products (AOPP), lipid peroxidation (MDA), and total thiol (T-SH) were determined in 157 T2DM patients (DM without complications n = 57, DM micro-vascular complications n = 53, DM macro-vascular complications n = 47) and 40 healthy controls.ResultsSerum AGE level increased significantly in various study groups in following manner: healthy control < DM without complications < DM-macro < DM-micro. Logistic regression analysis using diabetic complications as dependent variable showed significant association with AGE level and PON1 activity even after adjustment for confounding factors. Receiver-operating-characteristics curve analysis showed that 2-fold increased in glycation and 50% decrease in PON1 activity may lead to development of vascular complications in diabetic subjects. PCO, AOPP and MDA were higher and PON1 activity was lower in T2DM with complications than those without complications. Among diabetic patients AGEs showed significant positive correlation with HbA1C, MDA, AOPP, and negative correlation with PON1 activity and T-SH.ConclusionHigh serum AGE concentration and low PON1 activity may be considered as additional risk factor for development of vascular complications in T2DM. AGE formation plays significant role in induction of OS in diabetes.

► AGE level increased significantly in T2DM and more so in T2DM with complications.
► PON1 activity reduced significantly in all T2DM groups.
► An inverse relationship was viewed between PON1 activity and AGE level in T2DM.
► AGEs showed significant and positive correlation with oxidative stress markers in T2DM.
► 2-fold increase in AGE level and low PON1 activity may induce complications in T2DM.