Persistent MASLD Greatly Increases Diabetes and Cardiovascular Risks, Study Finds
A new nationwide cohort analysis published in Cardiovascular Diabetology reports that temporal patterns of metabolic dysfunction–associated steatotic liver disease (MASLD) strongly predict future type 2 diabetes (T2DM), cardiovascular disease (CVD), and mortality. Investigators from the Fatty Liver Research Group of the Korean Diabetes Association analyzed more than 5 million adults in the Korean National Health Insurance Service database to determine how changes in MASLD status influence long-term cardiometabolic outcomes.
Study Findings
In this population-based study, MASLD was defined using the fatty liver index (FLI), with a threshold of ≥60. Researchers compared FLI values over 2 health checkups spanning 2 years and categorized individuals into 4 groups: never MASLD, incident MASLD, regressed MASLD, and persistent MASLD. Outcomes included incident T2DM in the general population and myocardial infarction (MI), ischemic stroke, heart failure (HF), and all-cause mortality among individuals with existing T2DM. Models were adjusted for age, sex, smoking, alcohol use, and physical activity.
Among 4,397,808 adults without T2DM at baseline, 229,475 (5.2%) developed diabetes over a median 7.3-year follow-up. Persistent MASLD conveyed the highest risk, with a hazard ratio (HR) of 5.28 (95% CI, 5.22–5.34) versus those who never developed MASLD. Elevated risk was also seen in incident MASLD (HR, 3.30; 95% CI, 3.25–3.35) and regressed MASLD (HR, 2.87; 95% CI, 2.82–2.92) groups.
In a cohort of 636,520 adults with pre-existing T2DM followed for 6.2 years, persistent MASLD significantly increased the risk of HF (HR, 1.28; 95% CI, 1.25–1.32), MI (HR, 1.15; 95% CI, 1.10–1.20), stroke (HR, 1.14; 95% CI, 1.09–1.19), and all-cause mortality (HR, 1.11; 95% CI, 1.09–1.14). Incident and regressed MASLD were also associated with higher risks across all clinical endpoints, demonstrating that even improvement from MASLD does not fully normalize cardiometabolic risk.
Clinical Implications
These findings reinforce MASLD as a dynamic and clinically meaningful marker of metabolic health. The strong association between persistent MASLD and T2DM progression underscores the need for early identification and aggressive metabolic risk modification in at-risk individuals. For patients with established T2DM, MASLD status may offer additional prognostic information to guide cardiovascular risk stratification.
Importantly, elevated risks among individuals whose MASLD regressed suggest that historical MASLD exposure may have lasting metabolic consequences. Clinicians should therefore maintain vigilance even when liver fat indices improve. Integrated management—addressing obesity, insulin resistance, dyslipidemia, and lifestyle factors—may be essential to reducing long-term CVD and mortality in this population.
Temporal patterns of MASLD provide significant prognostic insight into diabetes development and cardiometabolic outcomes. Persistent MASLD confers the highest risk, but even incident or regressed MASLD elevates adverse event rates. The study highlights MASLD as a critical target for prevention and risk-reduction strategies.
Reference
Han E, Han KD, Lee YH, et al; Fatty Liver Research Group of the Korean Diabetes Association. Association of temporal MASLD with type 2 diabetes, cardiovascular disease and mortality. Cardiovasc Diabetol. 2025;24(1):289. doi:10.1186/s12933-025-02824-3.
