Advanced oxidative and glycoxidative protein damage markers in the elderly with type 2 diabetes.J Proteomics 2013; 92:313-22JP
We aimed to explore the association of advanced oxidation and advanced glycation of proteins, and their interrelations with endothelial nitric oxide synthesis, oxidative stress, metabolic profile as well as other atherosclerotic risk markers in prediabetic and diabetic elderly subjects. Advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), low-density lipoprotein susceptibility to oxidation (oxLDL) and nitric oxide metabolic pathway products (NOx) were assessed in subjects with impaired fasting glucose (prediabetes, IFG; n=90), and type 2 diabetes mellitus (T2DM, n=95) versus control subjects (n=88). Higher levels of AOPPs, AGEs, oxLDL, NOx, atherosclerosis risk markers, and insulin resistance were pointed out in IFG and T2DM groups compared with control. Strong positive associations (p<0.01) of AGEs with fasting glucose and HbA1c were found in both hyperglycemic groups, whereas AOPPs were significantly correlated (p<0.01) only in T2DM. In T2DM, AGEs and AOPPs significantly (p<0.01) correlated with insulin resistance index HOMA-IR, oxLDL and small LDL particle size (TG/HDL-C), and positively with NOx. Direct associations of AGEs and AOPPs with TC/HDL-C and oxLDL/HDL-C, and AGEs-AOPPs interrelations (p<0.01) were identified in IFG and T2DM groups. AGEs and AOPPs in combination with oxLDL and NOx could be important biomarkers for evaluating the association between diabetes and atherosclerotic disorders in aging diabetic patients.
In the present study we have made an attempt to approach the biological and clinical significance of the oxidative and glycoxidative protein damage, in subjects with prediabetes and type-2 diabetes mellitus. AGEs and AOPPs in combination with oxLDL and NOx appear to be important biomarkers for evaluating the association between diabetes and atherosclerotic disorders in aging diabetic patients. More importantly, this cluster of biomarkers that links the short term, "real time" metabolic impairment parameters (NOx, serum glucose, HOMA-IR, serum lipid profile) and the "metabolic memory" markers resulting from the long-term hyperglycemia and hyperlipidemia-induced oxidative stress (HbA1c, AGEs, AOPPs and oxLDL), could be valuable in predicting not only vascular complications in T2DM, but also the onset of diabetes, hence enabling therapeutic interventions from the early stages of diabetes. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine.