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