Irisin levels in patients with prediabetes mellitus: A case-control study and meta-analysis

doi:10.4239/wjd.120779

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Publication Name

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

Case Control Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Jul 15, 2026; 17(7): 120779
Published online Jul 15, 2026. doi: 10.4239/wjd.120779

Irisin levels in patients with prediabetes mellitus: A case-control study and meta-analysis

Li-Wen Song, Wen-Wen Huang, Li-Na Chang, Xin Wang, Qian-Qian Sun, Xiao-Long Wang, Qing He

Li-Wen Song, Li-Na Chang, Xin Wang, Qing He, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin 300052, China

Li-Wen Song, Department of Medical, Weifang People’s Hospital, Weifang 261041, Shandong Province, China

Wen-Wen Huang, Qian-Qian Sun, Department of Endocrinology, Weifang People’s Hospital, Weifang 261041, Shandong Province, China

Xiao-Long Wang, Department of Emergency, Weifang People’s Hospital, Weifang 261041, Shandong Province, China

Co-first authors: Li-Wen Song and Wen-Wen Huang.

Author contributions: Song LW and Huang WW contribute equally to this study as co-first authors; Song LW designed the study and developed the retrieve strategy; Huang WW and Wang X were responsible for searching and screening the summaries and titles, assessing the inclusion and exclusion criteria, generating data collection forms and extracting data, and evaluating the quality of the study; Chang LN and Sun QQ performed meta-analysis; Song LW and Wang XL drafted the article; He Q reviewed and revised the article; and all authors have read and approve the final manuscript.

AI contribution statement: No ChatGPT, Grammarly, DeepL or any other AI tools have been used in the whole process of manuscript writing, language polishing, data analysis, study design, result interpretation and image production. All content of the manuscript is independently completed by the authors.

Supported by Science and Technology Development Project of the Affiliated Hospital of Weifang Medical University Funds, No. 2023FYM015; and Tianjin Key Medical Discipline (Specialty) Construction Project, No. TJYXZDXK-3-002C.

Institutional review board statement: The study protocol was approved by the Ethics Committee of Tianjin Medical University General Hospital (Approval No. IRB2024-YX-139-01).

Informed consent statement: All subjects were provided with and signed an informed consent form.

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

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.

Data sharing statement: All data generated or analysed during this study are included in this published article. For further questions, please reach out to the corresponding authors.

Corresponding author: Qing He, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin 300052, China. heqing202301@tmu.edu.cn

Received: March 9, 2026
Revised: April 2, 2026
Accepted: May 14, 2026
Published online: July 15, 2026
Processing time: 123 Days and 23.6 Hours

Abstract

BACKGROUND

Circulating irisin, a myokine, has been inconsistently associated with prediabetes mellitus (PreDM), and its relationship with glucagon is unexplored. Methodological variability, particularly between different enzyme-linked immunosorbent assay (ELISA) kits, is hypothesized to be a primary source of these discrepancies. Therefore, we hypothesized that the reported irisin-PreDM association is critically confounded by assay methodology and inadequate adjustment for key metabolic factors.

AIM

To investigate circulating irisin in PreDM via a dual-study approach, evaluating methodological variability and metabolic confounders.

METHODS

A dual-study design was employed: (1) A systematic review and meta-analysis of observational studies; and (2) A single-center, exploratory case-control study of 35 participants (9 PreDM, 26 controls) from a tertiary hospital. Irisin was measured with two commercial ELISA kits (ELK and Elabscience). Key analyses included random-effects meta-analysis, multiple linear regression, Spearman correlation, and Bland-Altman analysis for inter-assay agreement.

RESULTS

The meta-analysis (8 studies, n = 788) found significantly lower irisin in PreDM (standardized mean difference = -0.524, 95% confidence interval: -0.897 to -0.152, P = 0.006) with high heterogeneity (I² = 86.7%). In the case-control study, unadjusted analysis showed higher irisin in PreDM with the Elabscience kit (median: 7386.3 pg/mL vs 6332.0 pg/mL, P = 0.045) but not the ELK kit. After adjusting for gender, body mass index, and fatty liver, the association was null for both kits. Bland-Altman analysis revealed poor inter-assay agreement (mean bias: 5837.25 pg/mL). Irisin correlated with fatty liver (ρ = 0.350, P = 0.039) and 0.5-hour glucose (ρ = 0.421, P = 0.012), but not with glucagon.

CONCLUSION

The irisin-PreDM relationship appears to be influenced by assay methodology and metabolic factors. Standardizing irisin measurement and adjusting for key confounders are important considerations for future research.

Keywords: Irisin; Prediabetes mellitus; Enzyme-linked immunosorbent assay; Methodological variability; Standardization; Case-control study; Meta-analysis

Core Tip: This study suggests that methodological variability between commercial enzyme-linked immunosorbent assay kits may contribute to the conflicting literature on circulating irisin in prediabetes, supported by poor inter-assay agreement in this cohort. After rigorously controlling for metabolic confounders, the observed association between prediabetes and irisin disappears, shifting the focus from irisin as a simple biomarker to the critical need for assay standardization and robust study design in future research.