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Life sciences · Journal article
Lipids in Health and Disease · November 3, 2026
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Abstract Background Insulin resistance (IR) plays a central role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). The insulin-to-HDL-C ratio (IHR), combining fasting insulin with high-density lipoprotein cholesterol (HDL-C), may serve as a simple, routine laboratory-derived surrogate marker of IR. We evaluated the association of the IHR with the prevalence and severity of MASLD and compared its diagnostic performance with established Insulin resistance indices. Methods This cross-sectional study analyzed 1,735 adults who underwent health screening with abdominal ultrasonography. Participants receiving antidiabetic medications were excluded to avoid confounding insulin measurements. MASLD was defined by the 2023 multi-society criteria as ultrasonographic hepatic steatosis plus ≥ cardiometabolic criterion. Participants were categorized into IHR quartiles (Q1–Q4). Associations were assessed using multivariable logistic regression and prespecified subgroup analyses. Diagnostic discrimination for MASLD was compared against HDL-C, insulin, Homeostatic model assessment of insulin resistance (HOMA-IR), the TG/HDL-C ratio, and the TG-glucose (TyG) index using the area under the receiver operating characteristic curve (AUROC) with DeLong tests. Results MASLD prevalence increased across IHR quartiles, from 13.6% in Q1 to 66.8% in Q4 (P for trend < 0.005), and was higher in men than in women (48.8% vs. 32.9%). Higher IHR was also independently associated with greater steatosis severity. In the multivariable-adjusted model, the odds ratio (OR) for MASLD in the highest versus lowest IHR quartile was 4.80 (95% CI, 3.24–7.17; P for trend < 0.005) and was consistent across subgroups of obesity, sex, dyslipidemia, and coronary artery calcification, though it was stronger in normotensive participants (P for interaction < 0.001). The IHR demonstrated high discriminative ability for MASLD (AUROC, 0.759; 95% CI, 0.737–0.782) outperforming HDL-C, insulin, and HOMA-IR (all P < 0.001), while performing comparably to the TyG index and TG/HDL-C ratio. Conclusions A higher IHR was independently associated with the prevalence and severity of MASLD. This association persisted among participants without clinically overt obesity, hypertension, or dyslipidemia. Given its diagnostic performance comparable or superior to established IR indices, IHR may serve as a simple and biologically meaningful surrogate marker for assessing the insulin resistance underlying MASLD.