Anthropometric and Metabolic Determinants of Multi-Organ Stress in Adults with Obesity: Application of the CaRaMeL-O...

Background: Obesity represents a multisystemic disorder that extends beyond metabolic dysfunction, involving hepatic, renal, and cardiovascular axes. This study introduces the Cardio-Reno-Metabolic-Liver-Obesity (CaRaMeL-O) framework as an integrated tool to assess multi-organ metabolic stress in adults with obesity. Methods: In this cross-sectional study, 287 adults with obesity (mean BMI 35.1 ± 4.6 kg/m²) were evaluated. The CaRaMeL-O score (0-13 points) incorporated metabolic (TyG index), hepatic (FIB-4, transaminases), and renal (eGFR, UACR) parameters, as well as classical and lifestyle risk factors. Participants were stratified into low, moderate, and high risk categories. Group comparisons were conducted using ANOVA and Kruskal-Wallis tests, while multivariate regressions identified independent predictors of FIB-4 and eGFR. Distributional characteristics were further analyzed using Weibull modeling. Results: Higher CaRaMeL-O scores were associated with a progressive increase in TyG (p < 0.001) and FIB-4 (p < 0.001), while eGFR showed a mild, nonsignificant downward trend. In multivariate models, age was the strongest predictor of FIB-4 (β_std = 0.33), whereas age, FIB-4, BMI, blood pressure, and UACR independently predicted eGFR. TyG did not remain significant after full adjustment. Weibull analysis revealed distinct distributional profiles, with TyG showing a narrow, homogeneous curve and FIB-4 and eGFR broader, right-skewed patterns. Conclusions: The CaRaMeL-O framework effectively captures inter-organ metabolic stress, demonstrating that hepatic and metabolic alterations precede overt renal decline. This integrated score may support early stratification and targeted prevention in obesity-related cardio-metabolic risk.