Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2025; 17(6): 107160
Published online Jun 27, 2025. doi: 10.4254/wjh.v17.i6.107160
Association between insulin and liver function tests, liver disease and cirrhosis in population-based cohorts with long term follow-up
Andreas Schult, Kirsten Mehlig, Kurt Svärdsudd, Sven Wallerstedt, Cecilia Björkelund, Per-Olof Hansson, Henrik Zetterberg, Jerzy Kaczynski
Andreas Schult, Sven Wallerstedt, Per-Olof Hansson, Jerzy Kaczynski, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41390, Västra Götaland, Sweden
Andreas Schult, Transplant Institute, Sahlgrenska University Hospital, Gothenburg 41345, Västra Götaland, Sweden
Kirsten Mehlig, Department of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg 40530, Västra Götaland, Sweden
Kurt Svärdsudd, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine Section, University Uppsala, Uppsala 75310, Sweden
Cecilia Björkelund, Primary Health Care/Department of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg 41390, Västra Götaland, Sweden
Per-Olof Hansson, Jerzy Kaczynski, Department of Medicine, Geriatrics and Emergency Medicine, Sahlgrenska University Hospital/Östra, Gothenburg 41685, Västra Götaland, Sweden
Henrik Zetterberg, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden, Gothenburg 41390, Västra Götaland, Sweden
Henrik Zetterberg, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, LN WC1N3BG, United Kingdom
Henrik Zetterberg, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 43180, Sweden
Author contributions: Schult A wrote the main manuscript and contributed to study design and statistical analyses; Mehlig K provided statistical support and revised the manuscript; Wallerstedt S and Kaczynski J contributed to concept and design of the study and revising the manuscript; Svärdsudd K, Björkelund C, Hansson PO and Zetterberg H provided data and revised the manuscript; all of the authors read and approved the final version of the manuscript to be published.
Institutional review board statement: The use of the male and female cohort data for the study was approved by Regional Ethical Review Boards.
Informed consent statement: All participants provided informed consent upon enrollment in the longitudinal studies.
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: Technical appendix, statistical code, and dataset available from the corresponding author at andreas.schult@vgregion.se.
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: Andreas Schult, MD, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 3, Gothenburg 41390, Västra Götaland, Sweden. andreas.schult@vgregion.se
Received: March 17, 2025
Revised: April 8, 2025
Accepted: May 27, 2025
Published online: June 27, 2025
Processing time: 101 Days and 15.7 Hours
Abstract
BACKGROUND

Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels. It is associated with fatty liver disease and elevated liver function tests (LFT) in cross-sectional studies, but data from cohort studies are scarce.

AIM

To investigate the association between insulin and pathological LFT, liver disease, and cirrhosis in a population-based retrospective cohort study.

METHODS

Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used. LFT were obtained at two time points 8 years to 24 years after baseline. Liver disease diagnoses were obtained from nationwide registries. The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.

RESULTS

Total follow-up was 54054 person-years for women and 27556 person-years for men. Insulin levels were positively correlated with elevated LFT during follow-up, whereas physical activity and coffee consumption were negatively correlated. Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease, adjusted hazard ratio (aHR) of 4.3 (95%CI: 1.6-14.6) and cirrhosis (aHR = 4.8, 95%CI: 1.6-14.6).

CONCLUSION

This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease. The results support the concept of metabolic dysfunction associated liver disease.

Keywords: Insulin; Liver function tests; Alcohol; Metabolic dysfunction associated steatotic liver disease; Liver cirrhosis

Core Tip: Insulin resistance is a cardiometabolic risk factor. There is a paucity of cohort studies examining the effect of insulin on liver function tests and liver disease. This cohort study followed 2085 participants for up to 24 years. High insulin levels were associated to elevated liver enzymes and clinical manifest liver disease.