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Synergistic Impact of Sarcopenia and T2DM on Mortality in Metabolic Dysfunction-Associated Steatotic Liver Disease

Qi Zhou1,2, Peiyan Liu3, Lixiang Li1,2

  • 1Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|December 9, 2025
PubMed

Insights

The combination of sarcopenia and type 2 diabetes mellitus (T2DM) significantly increases mortality risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This synergistic effect is particularly pronounced in individuals with advanced fibrosis.

Area of Science:

  • Hepatology
  • Metabolic Diseases
  • Geriatrics

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently co-occurs with type 2 diabetes mellitus (T2DM) and sarcopenia.
  • The combined impact of MASLD, T2DM, and sarcopenia on mortality is not well understood.

Purpose of the Study:

  • To investigate the interaction effects of sarcopenia and T2DM on mortality risk in patients with MASLD.
  • To quantify the synergistic impact of sarcopenia and T2DM on all-cause and cardiovascular disease (CVD) mortality.

Main Methods:

  • A cohort of 1987 MASLD patients was monitored over a median of 15 years.
  • Cox proportional hazard models and interaction measures (RERI, AP, SI) were used to assess mortality risk and interaction effects.
  • Stratified and sensitivity analyses were performed to evaluate effects in subgroups, including those with advanced fibrosis and non-MASLD patients.

Main Results:

  • Patients with both sarcopenia and T2DM had a 2.5-fold higher risk of all-cause death and a doubled risk of CVD death compared to those without either condition.
  • A significant synergistic effect of sarcopenia and T2DM on mortality was observed in MASLD patients with advanced fibrosis.
  • The combined effect of T2DM and sarcopenia accounted for 27% of all-cause deaths and 29% of CVD deaths in the MASLD cohort.

Conclusions:

  • Sarcopenia and T2DM comorbidity synergistically increase all-cause and CVD-related mortality in MASLD patients.
  • The synergistic mortality risk is particularly elevated in MASLD patients with advanced fibrosis.
  • This interaction effect on mortality was not observed in patients without MASLD.
Keywords:
T2DMdeathmetabolic dysfunction‐associated steatotic liver diseasesarcopenia

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