Which Surrogate Marker of Insulin Resistance Among Those Proposed in the Literature Better Predicts the Presence of Non-Metastatic Bladder Cancer?

Background: Recent evidence has shown that insulin resistance (IR), a hallmark of nonalcoholic fatty liver disease, predicts bladder cancer (BC) presence. However, the best surrogate marker of IR in predicting BC is still unclear. This study examined the relationships among ten surrogate markers of IR and the presence of BC. Methods: Data from 209 patients admitted to two urology departments from September 2021 to October 2024 were retrospectively analyzed. Individuals (median age 70 years) were divided into two groups (123 and 86 patients, respectively) based on the presence/absence after cystoscopy/TURB of non-metastatic BC. Univariate logistic regression was used to determine the relationships between groups, and the following IR parameters: Triglyceride-Glucose (TyG) index, TyG-BMI, HOMA-IR HOMAB, MetS-IR, Single Point Insulin Sensitivity Estimator, Disposition Index, non-HDL/HDL, TG/HDL-C ratio and Lipoprotein Combine Index. Stepwise logistic regressions were carried out to evaluate the significant predictions and LASSO regression to confirm any significant variable(s). The predictive value of the index test for coexistent BC was evaluated using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Results: The univariate analysis revealed that the TyG index and MetS-IR were associated with the BC presence. Specifically, the associations of the TyG index and MetS-IR were more significant in participants =/> 65 years old. In multivariate analysis, the stepwise logistic regression, evaluating the most representative variables at univariate analysis, revealed a prediction of BC by only TyG index (OR 2.51, p = 0.012), confirmed by LASSO regression, with an OR of 3.13, p = 0.004). Assessing the diagnostic reliability of TyG, it showed an interesting predictive value for the existence of BC (AUC = 0.60; 95% CI, 0.51-0.68, cut-off 8.50). Additionally, a restricted cubic spline model to fit the dose-response relationship between the values of the index text (TyG) and the BC evidenced the presence of a non-linear association, with a high predictive value of the first knot, corresponding to its 10th percentile. The decision curve analysis confirmed that the model (TyG) has utility in supporting clinical decisions. Conclusions: Compared to other surrogate markers of IR, the TyG index is effective in identifying individuals at risk for BC. A TyG threshold of 8.5 was highly sensitive for detecting BC subjects and may be suitable as an auxiliary diagnostic criterion for BC in adults, mainly if less than 65 years old.