Plasma glycation adducts and various RAGE isoforms are intricately associated with oxidative stress and inflammatory markers in type 2 diabetes patients with vascular complications

Abstract

Background: The secondary vascular complications in diabetes mellitus (DM) are contributed by acute as well as inflammatory responses which get activated due to interaction between glycation adducts and respective receptors.

Aim: The present work was performed to understand the relationship between Advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE) interaction with oxidative stress and inflammation in vascular complications.

Methods: For the present work we recruited 103 controls, 200 patients with type 2 DM, and 200 patients with Diabetic complications. Different Plasma glycation adducts (fructosamine, carbonyls, AGEs, β-amyloid content, free amino groups, and free thiol groups); RAGE isoforms, level of antioxidant such as glutathione, catalase activity, nitric oxide level, total antioxidant capacity, and superoxide dismutase activity, as well as oxidative markers, and expression of Nε-carboxymethyl-lysine (CML), different isoforms of RAGE, NF-κB, and inflammatory markers were analyzed.

Results: Glycation adducts were higher in DM patients and more elevated in nephropathy patients where free amino groups and thiol groups lowered as compared to controls. sRAGE levels and expression were increased mainly in nephropathy. CML expression was higher in nephropathy patients. The antioxidant profile indicates a reduced level of different antioxidants while increased lipid peroxidation and intracellular ROS generation in DM and much higher in nephropathy patients. Expression of membrane RAGE, NF-κB, and inflammatory markers showed a remarkably increased level in DM patients with nephropathy.

Conclusion: This work provides the first evidence of four different RAGE isoforms in diabetes and in complications. The glycation via the activation of RAGE, oxidative stress, and resultant inflammation plays a crucial role in the development of diabetic complications.

Keywords: Clinical diabetes; Glycation; Oxidative stress; RAGE isoforms.