IDDF2024-ABS-0086 Insulin resistance is associated with high-risk mash in individuals without diabetes

<h3>Background</h3> Currently, screening and evaluation methods for high-risk metabolic dysfunction-associated steatohepatitis (MASH) are still insufficient. We aimed to investigate the association of the surrogate markers of insulin resistance [homeostasis model assessment parameter of insulin resistance (HOMA-IR) and triglyceride–glucose index (TyG)] with incidents of high-risk MASH in the nondiabetic general population. <h3>Methods</h3> It’s a cross-sectional study based on NHANES 2017-2020. High-risk MASH was defined as a Fibroscan-AST (FAST) score ≥ 0.35. Logistic regression was used to assess the association between HOMA-IR and TyG index and the odds of high-risk MASH. Additionally, C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were utilized to assess the diagnostic ability for high-risk MASH by the addition of an insulin resistance index. <h3>Results</h3> A total of 2,717 adults were included (IDDF2024-ABS-0086 Figure 1), representing a sample of 176,136,538, of which the weighted average age was 44.62 years, 4.64% was high-risk MASH Both HOMR-IR and TyG were independently positively correlated with high-risk MASH (HOMR-IR: adjusted OR: 1.56, 95%CI: 1.18, 2.06; TyG: adjusted OR: 1.85, 95%CI: 1.14, 2.99). Subgroup analyses revealed that the association between HOMA-IR and high-risk MASH was stronger in older individuals (age ≥ 60 years, p for interaction = 0.027) (IDDF2024-ABS-0086 Figure 2), while the TyG index’s association was stronger in those with obesity (p for interaction = 0.033) (IDDF2024-ABS-0086 Figure 3). The addition of HOMA-IR or TyG to established diagnostic models, such as nonalcoholic fatty liver disease (NAFLD) fibrosis score, fibrosis-4, and aspartate aminotransferase-to-platelet ratio index, significantly improved the diagnostic performance for high-risk MASH, as evidenced by C-index values, NRI, IDI for both indices (IDDF2024-ABS-0086 Figure 4). <h3>Conclusions</h3> The insulin resistance, as measured by HOMA-IR and TyG, could be valuable in identifying individuals at risk for high-risk MASH, particularly in older adults and those with obesity, and may enhance the diagnostic accuracy of non-invasive NAFLD assessment tools for high-risk MASH. Further research, particularly in diverse populations and with prospective designs, is needed to confirm these associations and their clinical implications.