Serum uric acid to HDL-Chol ratio (UHR) is associated with insulin resistance/sensitivity in individuals without diabetes

Abstract Background The uric acid-to-HDL cholesterol ratio (UHR) is a promising non-insulin-based marker for metabolic risk, associated with type 2 diabetes, hypertension, hepatic steatosis, and cardiovascular disease. However, its utility in individuals with altered glucose tolerance remains unclear. Methods We investigated the relationship between UHR and insulin sensitivity in two independent cohorts. Sample 1 ( n = 1555) from the CATAMERI study, was stratified based on oral glucose tolerance test (OGTT) results, and Sample 2 ( n = 332) from the EUGENE2 project, with insulin sensitivity measured via euglycemic-hyperinsulinemic clamp. Results In Sample 1, UHR showed positive correlations with BMI, triglycerides, 2-hour plasma glucose, HOMA-IR, fasting plasma insulin ( p < 0.0001 for all) and with HbA1c ( p < 0.001), and negative correlations with Matsuda index ( p < 0.0001) and total cholesterol ( p = 0.019). Multivariable linear regression identified HOMA-IR (β = 0.100), Matsuda index (β=-0.146), InsAUC30/GluAUC30 (β = 0.120), and Stumvoll 1st-phase insulin secretion (β = 0.121) as independent UHR predictors. In Sample 2, bivariate analyses, adjusted for age, sex, and BMI, confirmed positive correlations between UHR and HbA1c ( p < 0.001), 2-hour post-load glucose ( p = 0.001), BMI, triglycerides, and fasting insulin ( p < 0.0001 for all) and a negative correlation with Clamp M (glucose disposal, p = 0.0003). Finally, multivariable regression of Clamp M variability (adjusted for age, sex, and BMI) demonstrated significant negative associations with UHR (β= -0.230) and BMI (β= -0.375). Conclusion These findings suggest that UHR, derived easily and inexpensively from routine clinical measurements, is a promising indicator of metabolic risk in individuals without diabetes. Its accessibility positions it as a potential tool for early diabetes prevention strategies, potentially reducing reliance on the OGTT.