Association of SPISE with prevalent and incident MASLD: a two-stage population-based study and development of a risk prediction model

Background The prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) is increasing, and the disease is often asymptomatic in its early stages. Insulin resistance is central, but fasting-insulin–based indices are impractical for routine screening. The single-point insulin sensitivity estimator (SPISE) is simple and inexpensive, but its longitudinal association with MASLD and predictive utility remain unclear. Methods A two-stage study was performed. Cross-sectional analyses examined SPISE and prevalent MASLD; longitudinal analyses among participants without MASLD at baseline assessed incident MASLD and developed prediction models. MASLD was defined as ultrasound-confirmed steatosis plus ≥1 cardiometabolic risk factor. Logistic regression estimated odds ratios (ORs) for prevalent MASLD; Hazard ratios (HRs) for incident MASLD were estimated using Cox proportional hazards models, with restricted cubic splines used to characterize non-linear exposure–response patterns. Improvement in prediction after adding SPISE was compared with TyG, METS-IR, and TG/HDL-C using NRI and IDI metrics. Discriminative ability and clinical net benefit were examined with time-dependent ROC analysis and decision curve analysis, respectively. Results Higher SPISE was independently associated with lower odds of prevalent MASLD (fully adjusted OR = 0.43, 95% CI 0.38–0.48). Higher SPISE also predicted lower incident MASLD risk (fully adjusted HR = 0.49, 95% CI 0.46–0.52), with a significant nonlinear association (P for non-linearity < 0.001). Adding SPISE to the fully adjusted base model produced the largest improvements in reclassification and discrimination (NRI = 0.363; IDI = 0.093; both p < 0.001). A SPISE-based model incorporating liver enzymes, bilirubin, and blood pressure showed good discrimination at 12 and 24 months (AUC = 0.859 and 0.886, respectively) and favorable clinical net benefit. Conclusion SPISE is independently and inversely associated with prevalent and incident MASLD and provides superior incremental predictive value versus common insulin resistance indices. External validation is warranted.