Action of metformin therapy against advanced glycation, oxidative stress and inflammation in type 2 diabetes patients: 3 months follow-up study

Background: Persistence hyperglycemia results in the formation of advanced glycation end products (AGEs) by non-enzymatic glycation. AGEs and their receptor RAGE play an important role in generation of inflammatory molecules and oxidative stress. Metformin regulates insulin responsive gene and helps to achieve glycemic control however, no extensive study reported about its role against glycation induced oxidative stress and vascular inflammation. Therefore, present work focused on clinical relevance of three months metformin therapy in type 2 diabetes mellitus patients against glycation induced oxidative stress and vascular inflammation. Methods: Among recruited 40 medicated-naive type 2 diabetes mellitus patients, 31 patients were continued with metformin therapy. Biomarkers of plasma protein glycation (fructosamine, protein carbonyls, beta-amyloid) antioxidants and oxidative stress markers (GSH, catalase, NO, PON-1, AOPP, LPO; RAGE isoforms (sRAGE, esRAGE); inflammatory markers (IL-6, TNF-alpha) were determined at baseline and after 3-months of treatment. The expression profile of membrane RAGE, NF-kappa B, CML was studied in PBMNCs and GLUT-1 in erythrocyte ghost by western blotting. Results: Metformin showed maximum percent declined from baseline to three months therapy in levels of fructosamine, beta-amyloid, sRAGE, inflammatory cytokines (IL-6, TNF-alpha) and percent increment in esRAGE and antioxidants levels. It showed reduced levels of IL-6 and TNF-alpha by declining expression of CML, membrane RAGE and NF-kappa B in type 2 diabetes mellitus patients after three months therapy. Conclusions: First report in Indian diabetes mellitus patients, where metformin showed effective inhibition against glycation and receptor mediated cellular inflammation. However, these findings need to be tested in a randomized trial. (c) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.