Association of serum bile acid profiles with the risk of gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus

doi:10.4239/wjd.v17.i2.112859

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Diabetes. Feb 15, 2026; 17(2): 112859
Published online Feb 15, 2026. doi: 10.4239/wjd.v17.i2.112859

Association of serum bile acid profiles with the risk of gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus

Ke-Ying Zhu, Si-Jing Wang, Jie Li, Pan-Pan Ma, Su-Su Feng, Lin Guo, Yi-Bing Lu, Li Dong, Da-Fa Ding

Ke-Ying Zhu, Si-Jing Wang, Jie Li, Pan-Pan Ma, Su-Su Feng, Lin Guo, Yi-Bing Lu, Da-Fa Ding, Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China

Li Dong, Department of Endocrinology, Nanjing Red Cross Hospital, Nanjing 210001, Jiangsu Province, China

Co-first authors: Ke-Ying Zhu and Si-Jing Wang.

Co-corresponding authors: Li Dong and Da-Fa Ding.

Author contributions: Ding DF and Zhu KY designed the research; Wang SJ, Zhu KY, Li J, Ma PP, Feng SS, and Guo L performed the research; Wang SJ contributed new reagents or analytic tools; Wang SJ analyzed data; Wang SJ and Zhu KY wrote the paper; Lu YB, Li D, and Ding DF were involved in reviewing and editing; All authors read and agreed to the published version of the manuscript. Zhu KY and Wang SJ contributed equally to this work as co-first authors. Ding DF and Li D have contributed significantly to this work and share corresponding authorship. Ding DF was primarily responsible for the overall experimental design, study coordination, and data collection, forming the core of the research execution. Li D played a critical role in data auditing, verification, and ensuring data integrity and quality control throughout the analysis. Their combined expertise and complementary responsibilities were essential to the completion and rigor of this study. Therefore, we believe it is appropriate and justified to designate them both as corresponding authors.

Supported by Scientific Research Projects of Jiangsu Provincial Health and Health Commission, No. ZDB2020034 and No. M2021056.

Institutional review board statement: All experimental protocols were approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing Medical University, China (No. 4-KY-232-01 and date of approval September 30, 2024).

Informed consent statement: Due to the retrospective and low-risk nature of this study, the ethics committee waived the need for written informed consent.

Conflict-of-interest statement: The authors declare no conflict of interest.

Data sharing statement: Consent was not obtained but the presented data are anonymized and risk of identification is low

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, MD, Chief Physician, 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: August 8, 2025
Revised: September 22, 2025
Accepted: November 20, 2025
Published online: February 15, 2026
Processing time: 183 Days and 4 Hours

Abstract

BACKGROUND

Diabetic gastrointestinal autonomic neuropathy (DGAN) is a common yet underrecognized manifestation of diabetic neuropathy. However, the clinical correlations and associated alterations of serum bile acid (BA) metabolism with DGAN remain unclear.

AIM

To identify potential metabolite biomarkers capable of identifying DGAN among patients with type 2 diabetes mellitus (T2DM).

METHODS

This cross-sectional study included 26 patients with clinically defined DGAN and 69 patients with uncomplicated T2DM. Fifteen individual BAs were quantified in fasting serum using liquid chromatography-tandem mass spectrometry. Gastrointestinal symptoms were scored using the Gastrointestinal Symptom Rating Scale. Spearman’s correlation, multivariable logistic regression, receiver operating characteristic, and decision curve analyses were used to explore the associations and build a predictive nomogram.

RESULTS

Orthogonal partial least squares discriminant analysis of serum BAs revealed clear separation between the T2DM and DGAN groups, identifying taurolithocholic acid (TLCA) as the key discriminator (variable importance in projection > 1, fold change < 0.5). Univariate logistic regression identified age, body mass index, hemoglobin, fasting/2-h C-peptide, albumin, and TLCA levels as protective factors and the urinary albumin-to-creatinine ratio as a risk factor. After multivariate adjustment age, fasting C-peptide levels, and TLCA levels remained independently associated with DGAN. Receiver operating characteristic analysis yielded areas under the curve of 0.651, 0.760, and 0.678 for age, fasting C-peptide, and TLCA, respectively, and the three variables collectively had an area under the curve of 0.970 (95% confidence interval: 0.937-1.000). Decision curve analysis confirmed the clinical net benefit across threshold probabilities of 9%-68%. The derived nomogram displayed excellent calibration and net clinical benefits for the model.

CONCLUSION

These findings highlighted the association between altered BA profiles and DGAN in patients with T2DM. Combining BA profiling with conventional clinical data could facilitate the early identification of DGAN and offer new insights into early screening and BA-targeted interventions. While these findings offer valuable insights, they should nevertheless be viewed as hypothesis-generating and require further validation in larger, multicenter cohorts.

Keywords: Type 2 diabetes mellitus; Diabetic gastrointestinal autonomic neuropathy; Serum bile acids profiles; Gastrointestinal Symptom Rating Scale

Core Tip: This study revealed an association between altered bile acid (BA) profiles and diabetic gastrointestinal autonomic neuropathy. Combining BA profiling with conventional clinical data could facilitate the early identification of DGAN and offer new insights into early screening and BA-targeted interventions.