Assessment of triglyceride glucose index and triglyceride to HDL cholesterol ratio as markers of insulin resistance defined by the Homeostatic Model Assessment 2 in Middle Eastern adults with excess adiposity

Background. Insulin resistance (IR) drives early cardiometabolic risk in populations with high adiposity. Simple fasting markers, such as the triglyceride-glucose (TyG) index and the triglyceride-to-HDL cholesterol ratio (TG/ HDL-C), may be helpful. Still, their performance against the updated, non-linear Homeostatic Model Assessment 2 (HOMA2) model in Middle Eastern adults remains unclear. Objectives. Compare TyG versus TG/HDL-C for HOMA2-defined IR; test modification by Body Mass Index (BMI) (overweight vs. obesity); and evaluate discrimination, calibration, and clinical utility. Methods. Cross-sectional study of 140 adults without diabetes with overweight/ obesity. Fasting triglycerides, HDL-C, glucose, and insulin were assayed under quality control; HOMA2-IR, %S, and %B were derived. Multivariable linear models (per-SD predictors) adjusted for age, sex, and BMI; multiplicative interactions probed effect modification. Higher IR was defined as the sex-specific top quartile of HOMA2-IR. Discrimination (Area Under the Curve AUC; DeLong test), calibration (intercept, slope, Brier), decision-curve analysis (DCA), multiple imputation (20 datasets), and prespecified sensitivity checks were performed. Results. TyG independently tracked higher HOMA2-IR (β=0.127 per SD; 95% CI 0.033-0.220; p=0.0078), whereas TG/HDL-C was null. TyG×BMI interaction was significant (p=0.0011): negligible in overweight (β≈0.01; p=0.85) but strong in obesity (β=0.29; p<0.001). Discrimination was similar (AUC TyG 0.714 vs TG/HDL-C 0.707; ΔAUC=0.007; p=0.801). DCA showed a higher net benefit for TyG, especially TyG+BMI, across thresholds of 0.20-0.60. Calibration was acceptable; bootstrap-validated metrics and extensive sensitivity analyses were consistent. Conclusions. In adults without diabetes with excess adiposity, TyG captures HOMA2-defined IR more consistently than TG/HDL-C, with the greatest incremental value in obesity. As a low-cost fasting metric, TyG, particularly when combined with BMI, may refine triage for further evaluation; external validation in regional cohorts is warranted.