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