Lifestyle mediates the association between normal-weight visceral obesity and MASLD in older adults with hypertension and diabetes.

OBJECTIVE: Older adults with coexisting hypertension and type 2 diabetes are at high risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Normal-weight visceral obesity (NWVO)-excess visceral fat despite normal body mass index and waist circumference-is an overlooked risk factor. Lifestyle is modifiable, but its role in explaining the NWVO-MASLD association is unknown. We quantified the proportion of this association statistically mediated by unhealthy lifestyle patterns. METHODS: This retrospective cohort study included 26,289 adults aged ≥50 years with hypertension and type 2 diabetes from the Shenzhen National Basic Public Health Services Program (2010-2023). NWVO was defined using the Chinese Visceral Adiposity Index alongside normal body size criteria. MASLD was diagnosed by ultrasound and cardiometabolic criteria. A composite lifestyle score (physical activity, alcohol, smoking, dietary salt intake) was derived. We applied the generalized front-door formula for causal mediation analysis to estimate the path-specific effect of NWVO on MASLD incidence explained by lifestyle, robust to unmeasured confounding. RESULTS: Over a mean 5.5-year follow-up, NWVO was associated with a significantly increased MASLD risk (adjusted HR: 1.82, 95% CI: 1.76, 1.89). In marginal models, NWVO was associated with a 2.35-fold higher risk of having an unhealthy lifestyle (2.25, 2.44) and an 11.2% higher MASLD risk (8.7, 13.8). Using the front-door formula, unhealthy lifestyle statistically explained 19.8% (12.1, 33.6) of the total NWVO-MASLD effect, corresponding to a mediated risk increase of 41.2% (3.5, 92.7). CONCLUSION: In this multimorbid older population, NWVO is a significant MASLD risk factor, and modifiable lifestyle patterns account for approximately one-fifth of this association. Our findings support integrating visceral adiposity assessment into routine care and implementing multifaceted lifestyle interventions-targeting diet, physical activity, and substance use-to reduce the burden of MASLD in aging populations with metabolic comorbidities.