Bidirectional relationship between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus

Authors

  • Alessandro Mantovani Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore – Don Calabria Hospital, Negrar di Valpolicella, Italy https://orcid.org/0000-0002-7271-6329
  • Riccardo Morandin Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore – Don Calabria Hospital, Negrar di Valpolicella, Italy https://orcid.org/0009-0005-4213-2102
  • Nicoletta Rolli Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore – Don Calabria Hospital, Negrar di Valpolicella, Italy https://orcid.org/0009-0004-6949-9222
  • Elisa Molinaroli Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore – Don Calabria Hospital, Negrar di Valpolicella, Italy
  • Giovanni Targher Metabolic Diseases Research Unit, IRCCS Sacro Cuore – Don Calabria Hospital, Viale Luigi Rizzardi 4, 37024 Negrar di Valpolicella, Italy; E-mail: giovanni.targher@univr.it https://orcid.org/0000-0002-4325-3900

DOI:

https://doi.org/10.17179/excli2026-9462

Keywords:

MASLD, type 2 diabetes, liver fat, review

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are two common, interconnected conditions that pose a major global health challenge. The worldwide prevalence of MASLD among individuals with T2DM exceeds 60 %, with a substantial proportion of cases having metabolic dysfunction-associated steatohepatitis (MASH) and an increased risk of liver-related complications, such as cirrhosis, liver failure, or hepatocellular carcinoma. The coexistence of MASLD and T2DM is also associated with poorer glycemic control and a higher risk of cardiovascular events, chronic kidney disease, and mortality. Notably, MASLD increases the risk of developing T2DM, with risk rising stepwise with liver disease severity, especially liver fibrosis. The close bidirectional relationship between MASLD and T2DM creates a vicious cycle that drives liver disease progression, worsens insulin resistance, and impairs glucose metabolism. This likely reflects shared underlying mechanisms, including insulin resistance, low-grade inflammation, lipotoxicity, adipose tissue dysfunction, and an altered gut–liver axis. Screening strategies are crucial for MASLD and T2DM, with current guidelines recommending assessment of liver fibrosis in all individuals with T2DM and regular screening for dysglycemia in those with MASLD. Pharmacological treatments, especially incretin-based therapies, sodium-glucose cotransporter 2 inhibitors, and resmetirom, show significant benefits across metabolic, hepatic, and extrahepatic outcomes. Overall, recognizing and addressing the bidirectional relationship between MASLD and T2DM is essential for better risk stratification, earlier intervention, and reduced long-term hepatic and extrahepatic complications. This narrative review summarizes current evidence on the bidirectional relationship between MASLD and T2DM, discussing epidemiological data, pathophysiological mechanisms, clinical implications, and therapeutic options.

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Published

2026-06-12

How to Cite

Mantovani, A., Morandin, R., Rolli, N., Molinaroli, E., & Targher, G. (2026). Bidirectional relationship between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus. EXCLI Journal, 25, 803–821. https://doi.org/10.17179/excli2026-9462

Issue

Vol. 25 (2026)

Section

Review articles

Categories

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Copyright (c) 2026 Alessandro Mantovani, Riccardo Morandin, Nicoletta Rolli, Elisa Molinaroli, Giovanni Targher

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