Fasting blood glucose to high-density lipoprotein cholesterol ratio and MASLD risk: non-linear association and BMI mediation in non-diabetic adults

Background: The fasting blood glucose (FBG) to high-density lipoprotein cholesterol (HDL-C) ratio (GHR) integrates glucose and lipid metabolism, but its association with metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to investigate the relationship between GHR and MASLD and to quantify the mediating role of body mass index (BMI) in non-diabetic adults. Methods: This cross-sectional study included 13,682 non-diabetic Japanese adults from the NAGALA cohort (2004-2015). Logistic regression was used to examine the association between GHR and MASLD risk, while generalized additive models (GAMs) and smooth curve fitting were used to investigate their non-linear relationship. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of GHR for MASLD, and mediation analysis was conducted to assess the mediating effect of BMI in this association. Results: = 2,087). GHR was significantly higher in participants with MASLD (4.93 ± 1.14 vs. 3.59 ± 1.07). After multivariable adjustment, each 1-unit increase in GHR was associated with a 23% higher risk of MASLD (OR 1.23, 95% CI 1.15-1.31). A threshold effect was identified, with the risk escalating progressively when GHR < 4.62. GHR showed good discriminative ability with an AUC of 0.815 (95% CI: 0.806-0.824), significantly outperforming FBG alone (AUC 0.727) and HDL-C alone (AUC 0.787). Mediation analysis revealed that BMI accounted for 59.86% of the total association between GHR and MASLD risk as a potential intermediary factor. Conclusion: Among non-diabetic Japanese adults, elevated GHR is independently associated with an increased risk of MASLD, and BMI acts as a potential partial intermediary factor in this observed association. GHR may serve as a simple, cost-effective initial screening tool for MASLD in non-diabetic clinical practice, particularly in individuals without severe obesity or hypertriglyceridemia.