Type 2 diabetes, sex and metabolic dysfunction-associated steatotic liver disease

doi:10.4239/wjd.v17.i5.119756

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May 15, 2026 (publication date) through May 14, 2026

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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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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. May 15, 2026; 17(5): 119756
Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.119756

Type 2 diabetes, sex and metabolic dysfunction-associated steatotic liver disease

Amedeo Lonardo, Mohamad Jamalinia, Ralf Weiskirchen

Amedeo Lonardo, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena (2023), Modena 41126, Provincia di Modena, Italy

Mohamad Jamalinia, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences Shiraz Iran, Shiraz University of Medical Sciences, Shiraz 71345, Fars Province, Iran

Ralf Weiskirchen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Aachen 52074, North Rhine-Westphalia, Germany

Author contributions: Lonardo A, Jamalinia M, and Weiskirchen R each made substantial and equal contributions to the study’s design, data acquisition and analysis, as well as the preparation and writing of this manuscript.

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

Corresponding author: Amedeo Lonardo, MD, Doctor, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena (2023), Via Giardini 1355, Modena 41126, Provincia di Modena, Italy. a.lonardo@libero.it

Received: February 5, 2026
Revised: February 28, 2026
Accepted: March 30, 2026
Published online: May 15, 2026
Processing time: 96 Days and 0.1 Hours

Abstract

This review examines the role of sex in modulating the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and various components of type 2 diabetes (T2D) pathobiology. Data suggest that women with prediabetes and diabetes have a greater risk of MASLD compared to men. Furthermore, postmenopausal women with T2D demonstrate a high prevalence of advanced MASLD, and the female sex appears to interact with T2D to enhance the detrimental effects of the PNPLA3 rs738409 variant on adverse liver outcomes. MASLD serves as a risk factor for incident T2D, and the predictive biomarkers for diabetes onset may vary by sex. Additionally, sex may influence the likelihood of diabetic complications, while MASLD appears to more significantly impact the development of coronary artery disease in women. Finally, sex differences in the management of T2D among individuals with MASLD are analyzed.

Keywords: Steatotic liver disease; Metabolic dysfunction-associated steatotic liver disease; Metabolic syndrome; Sex; Type 2 diabetes

Core Tip: Animal models indicate that males are more susceptible to obesity and metabolic disorders. Men, especially those in middle age, exhibit higher rates of type 2 diabetes. Sex also influences risk factors for atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Among individuals with diabetes, women’s risk for ASCVD and MASLD increases over time as the protective effects of sex hormones diminish. While estradiol has demonstrated protective properties, further investigation into the roles of sex chromosomes and epigenetic factors is warranted. Recognizing these distinctions is essential for advancing precision medicine and optimizing diabetes management.