Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2023; 14(12): 1754-1765
Published online Dec 15, 2023. doi: 10.4239/wjd.v14.i12.1754
Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients
Dharmsheel Shrivastav, Desh Deepak Singh, Rashid Mir, Pratishtha Mehra, Vimal Mehta, Pradeep Kumar Dabla
Dharmsheel Shrivastav, Desh Deepak Singh, Amity Institute of Biotechnology, Amity University, Jaipur 303002, Rajasthan, India
Dharmsheel Shrivastav, Pradeep Kumar Dabla, Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
Rashid Mir, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, India
Pratishtha Mehra, Vimal Mehta, Department of Cardiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
Co-corresponding authors: Pradeep Kumar Dabla and Desh Deepak Singh.
Author contributions: Dabla PK and Singh DD conceived, designed the study protocol; Shrivastav D, Dabla PK and Mehta V were involved in the data collection; Shrivastav D, Dabla PK, Singh DD, Mir R, Mehta V and Mehra P analyzed the data; Shrivastav D drafted the manuscript; Dabla PK, Singh DD, Mir R, Mehta V and Mehra P refined the manuscript; All authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. The reasons for designating Dabla PK and Singh DD as co-corresponding authors are that they conceived and designed the study protocol, the collaborative effort, the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper and ensuring effective communication post submission. Further, the overall research team encompassed authors with a variety of expertise and skills from different fields with important contributions to complete the study and the resultant paper. This promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Dabla PK, Singh DD as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, contributions, and diversity.
Institutional review board statement: The study was approved by the ethics committee of the Institutional Ethical Committee of Maulana Azad Medical College and associated hospitals, Delhi, India (F1/IEC/MAMC/85/03/21/no.422; Dt-30.08.2021).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. All authors declare no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at pradeep_dabla@yahoo.com.
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: Pradeep Kumar Dabla, MD, Professor, Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, J L N Marg, Delhi 110002, India. pradeep_dabla@yahoo.com
Received: August 21, 2023
Peer-review started: August 21, 2023
First decision: September 29, 2023
Revised: October 11, 2023
Accepted: November 3, 2023
Article in press: November 3, 2023
Published online: December 15, 2023
Processing time: 114 Days and 22.1 Hours
ARTICLE HIGHLIGHTS
Research background

Coronary artery disease (CAD) is a widespread global health issue, responsible for a significant number of deaths. India bears a substantial burden, contributing to approximately one-fifth of CAD-related fatalities. The development of CAD has been closely linked to the accumulation of Nε-carboxymethyl-lysine (CML) in the heart muscle, a phenomenon associated with fibrosis. Understanding the role of CML in CAD development is crucial for combating this life-threatening condition.

Research motivation

This study is motivated by the need to shed light on the factors contributing to CAD, especially in the context of diabetes. CAD is a complex disease, and understanding its underlying mechanisms can help in early diagnosis and more effective management. Diabetes is a significant risk factor for CAD, and investigating the interplay between CML, inflammatory markers, and CAD in individuals with and without diabetes can provide valuable insights into its pathogenesis.

Research objectives

The primary objective of this research was to evaluate the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients, differentiating between diabetic and non-diabetes patients. The study aimed to identify potential links between CML, diabetes, and CAD and to assess if these factors could serve as predictive biomarkers.

Research methods

To achieve these objectives, this study enrolled 200 consecutive CAD patients undergoing coronary angiography. The patients were categorized into two groups based on their serum glycosylated hemoglobin (HbA1c) levels, with diabetic CAD patients (group I) having HbA1c levels of ≥ 6.5 and non-diabetic CAD patients (group II) with HbA1c levels < 6.5. Various parameters, including lipoprotein levels, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nitric oxide levels, were analyzed to assess the differences between the two groups.

Research results

The study revealed several significant findings. Group I, comprising 81 males and 19 females, had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II, consisting of 89 males and 11 females, had a mean age of 53.2 ± 10.3 years. Group I exhibited more severe CAD, with a higher percentage of patients suffering from triple vessel disease and more severe stenosis in the left anterior descending coronary artery compared to group II. Group I patients also had a larger left atrium diameter. Significantly, group I patients displayed higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide compared to group II patients. The study also demonstrated strong correlations between CML and inflammatory markers, with CML showing a significant positive correlation with IL-6 (r = 0.596, P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Odds ratio analysis indicated that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at both unadjusted and adjusted levels when considering various covariates.

Research conclusions

CML and inflammatory markers, particularly IL-6 and TNF-α, may play a significant role in the development of CAD, especially in individuals with diabetes. These findings suggest that CML and inflammatory markers can serve as potential biomarkers for predicting CAD, not only in diabetic patients but also in non-diabetic individuals. Understanding the mechanisms linking CML and inflammation to CAD provides valuable insights for improved CAD diagnosis, risk assessment, and management, which can ultimately contribute to reducing the burden of this life-threatening disease.

Research perspectives

Future studies should explore interventions targeting CML and inflammatory markers to mitigate CAD risk. Investigating therapeutic strategies and diagnostic tools based on these biomarkers can aid in early CAD detection and personalized treatment, potentially reducing CAD-related mortality rates globally.