Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2023; 14(8): 1146-1162
Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1146
Advanced glycation end products: Key mediator and therapeutic target of cardiovascular complications in diabetes
Savita Bansal, Archana Burman, Asok Kumar Tripathi
Savita Bansal, Department of Biochemistry, Institute of Home Sciences, University of Delhi, New Delhi 110016, India
Archana Burman, Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi 110016, India
Asok Kumar Tripathi, Department of Biochemistry, University College of Medical Sciences, University of Delhi, New Delhi 110095, India
Author contributions: Bansal S frames the review article; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Savita Bansal, PhD, Assistant Professor, Department of Biochemistry, Institute of Home Sciences, University of Delhi, Hauz Khas, New Delhi 110016, India. savita.bansal@ihe.du.ac.in
Received: January 29, 2023
Peer-review started: January 29, 2023
First decision: March 1, 2023
Revised: March 21, 2023
Accepted: May 22, 2023
Article in press: May 22, 2023
Published online: August 15, 2023
Processing time: 193 Days and 22.7 Hours
Abstract

The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns. Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality. The cardiovascular diseases that accompany diabetes include angina, myocardial infarction, stroke, peripheral artery disease, and congestive heart failure. Among the various risk factors generated secondary to hyperglycemic situations, advanced glycation end products (AGEs) are one of the important targets for future diagnosis and prevention of diabetes. In the last decade, AGEs have drawn a lot of attention due to their involvement in diabetic patho-physiology. AGEs can be derived exogenously and endogenously through various pathways. These are a non-homogeneous, chemically diverse group of compounds formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein, lipids, and nucleic acid. AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways. At the cellular level, they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation, inflammation, cellular proliferation, and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics. AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins; altering their structure, stability, and functions. Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities. In the present review, we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications. Furthermore, this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.

Keywords: Type 2 diabetes mellitus; Cardiovascular complications; Hyperglycemia; Advanced glycation end products; Reactive oxygen species; Oxidative stress; Endothelial cells; Receptor of advanced glycation end products; Anti-advanced glycation end products strategies

Core tip: Cardiovascular diseases (CVDs) in type 2 diabetes mellitus impose a clinical and an economic burden on the healthcare system. Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities. The present manuscript reports the clinical relevance of estimating advanced glycation end products (AGEs) in diabetes. The deleterious effects of AGEs include many important biochemical reactions central to the development and progression of cardiovascular complications in diabetes. Therefore, AGEs are one of the important targets for future diagnosis and prevention of diabetes. The epidemiology of CVD in diabetes, AGEs as a crucial mediator of diabetic CVD, and an overview of different strategies for countering the accumulation of AGEs is discussed along with new therapeutic interventions to ameliorate their effects.