Evaluation of the lipid accumulation product for MASLD risk stratification in type 2 diabetes: establishing sex-specific thresholds and clinical utility

BACKGROUND: While visceral adiposity and lipid dysregulation are established drivers of metabolic dysfunction-associated steatotic liver disease (MASLD), the clinical utility of the lipid accumulation product (LAP) for identifying prevalent MASLD in patients with type 2 diabetes mellitus (T2DM) remains insufficiently characterized. This study aimed to characterize the dose-response relationship between LAP and MASLD in T2DM, establish optimal sex-specific diagnostic thresholds, and evaluate its clinical net benefit to guide non-invasive screening. METHODS: LAP was prioritized using the Boruta algorithm. Diagnostic cut-offs were determined via ROC analysis. The mathematical reliability of these thresholds was evaluated using 1,000-run stratified bootstrapping (internal validation), while the biological generalizability of LAP was further examined in an independent NHANES cohort (external validation). The dose-response relationship was characterized by restricted cubic splines (RCS). Clinical utility and stability were assessed using decision curve analysis (DCA) and subgroup analyses. RESULTS: LAP. DCA demonstrated a consistently higher net benefit for the LAP-based model over the "screen-all" strategy at threshold probabilities > 0.20. Subgroup analyses confirmed robustness across age and BMI strata, with the highest discriminative power in patients aged < 55 years (AUC 0.855) and reliable performance in non-obese individuals (AUC 0.711). External analysis in the NHANES cohort (N = 630) demonstrated consistent independent associations between LAP and MASLD risk (P < 0.05). CONCLUSIONS: LAP is a robust linear predictor of MASLD in T2DM. Implementing tailored thresholds provides superior diagnostic precision and clinical net benefit, particularly for younger and non-obese populations, supporting its use as a prioritized non-invasive screening tool.