Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2024; 15(5): 898-913
Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.898
Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients
Su-Su Feng, Si-Jing Wang, Lin Guo, Pan-Pan Ma, Xiao-Long Ye, Ming-Lin Pan, Bo Hang, Jian-Hua Mao, Antoine M Snijders, Yi-Bing Lu, Da-Fa Ding
Su-Su Feng, Si-Jing Wang, Lin Guo, Pan-Pan Ma, Xiao-Long Ye, Ming-Lin Pan, Yi-Bing Lu, Da-Fa Ding, Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
Bo Hang, Jian-Hua Mao, Antoine M Snijders, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
Co-first authors: Su-Su Feng and Si-Jing Wang.
Co-corresponding authors: Da-Fa Ding and Yi-Bing Lu.
Author contributions: Feng SS, Wang SJ, Lu YB, and Ding DF conceived, designed and refined the study protocol; Pan ML, Ye XL, Lu YB, and Ding DF recruited patients; Feng SS, Wang SJ, Guo L, and Ma PP collected the data and processed the samples; Feng SS, Wang SJ, and Snijders AM analyzed and interpreted the data; Hang B, Snijders AM, and Mao JH reviewed the statistical methods of this study; Feng SS and Wang SJ drafted the manuscript; and all authors read and approved the final manuscript; Feng SS and Wang SJ contributed equally to this work as co-first authors; Ding DF and Lu YB contributed equally to this work as co-corresponding authors. The reasons for designating Ding DF and Lu YB as co-corresponding authors are threefold. First, the research presented in our manuscript is the result of a concerted collaborative effort involving a team of researchers with diverse expertise. The designation of co-corresponding authors is essential to accurately reflect the shared responsibilities and contributions of all team members. This approach ensures a fair representation of the collective efforts invested in the research project. Second, our research team encompasses individuals with varied backgrounds and expertise, contributing to a comprehensive and nuanced exploration of the research topic. By appointing co-corresponding authors, we aim to acknowledge and highlight the diversity of skills and perspectives brought to the study. Third, throughout the entirety of the research process, Ding DF and Lu YB have made substantial and equal contributions to the manuscript. Recognizing their co-equal roles through the designation of co-corresponding authors is not only an acknowledgment of their individual efforts but also a testament to the collaborative spirit that defines our research. In summary, we believe that designating Ding DF and Lu YB as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, diversity of expertise, and equal contributions.
Supported by the Scientific Research Projects of Jiangsu Provincial Health and Health Commission, No. ZDB2020034 and No. M2021056.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing Medical University (approval No. 2023-KY-155-01).
Informed consent statement: Informed consent was waived due to the retrospective nature of this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used in this study can be obtained from the corresponding author upon reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Da-Fa Ding, PhD, Associate Chief Physician, Associate Professor, Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing 210011, Jiangsu Province, China. dingdafa@njmu.edu.cn
Received: January 4, 2024
Peer-review started: January 4, 2024
First decision: January 17, 2024
Revised: January 29, 2024
Accepted: March 14, 2024
Article in press: March 14, 2024
Published online: May 15, 2024
Processing time: 126 Days and 20 Hours
Abstract
BACKGROUND

The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.

AIM

To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.

METHODS

A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.

RESULTS

Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.

CONCLUSION

This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

Keywords: Bile acid; Non-alcoholic fatty liver disease; Type 2 diabetes mellitus; Unsaturated fatty acid

Core Tip: In the present study, we delineate notable distinctions in serum bile acid (BA) and unsaturated fatty acid (UFA) profiles between individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD) and those with T2DM alone. This first large-scale investigation links BA and UFA to NAFLD risk in T2DM patients, with the overarching objective of identifying predictive biomarkers and elucidating their connection to clinically relevant liver fibrosis in the context of NAFLD.