Association of the TyG–GGT index, a novel insulin resistance marker, with incident diabetes mellitus: a large-scale retrospective cohort study

Objective: Research on the association between TyG-GGT index and diabetes mellitus (DM) risk remains scarce. This study aimed to investigate the relationship between TyG-GGT and DM incidence. Methods: This retrospective cohort investigation enrolled 8,678 participants who underwent comprehensive health screenings at Kuichong People's Hospital in Shenzhen from 2018 through 2023. Cox proportional hazards regression models were employed to assess the association between TyG-GGT and DM risk, and Cox proportional hazards regression model with restricted cubic spline functions was used to evaluate non-linear relationships. Subgroup analyses and sensitivity analyses further verified the stability of these findings. Finally, receiver operating characteristic (ROC) curve methodology and time-dependent ROC analysis were performed to determine the predictive capacity of TyG-GGT for incident DM within a 5-year period. Results: Following multivariable adjustments, higher TyG-GGT levels were found to be associated with elevated DM risk, demonstrating an HR of 1.116 (95% CI: 1.041-1.196) per 50-unit increase in TyG-GGT. Additionally, a non-linear association between them was observed, exhibiting a threshold value at 380. When below this inflection point, the HR per 50-unit increase in TyG-GGT was 1.723 (95% CI: 1.500-1.979), while above this value the association was not statistically significant. Additionally, in predicting DM risk, TyG-GGT had the highest AUC value (0.732), while the AUC values of TG (0.635), GGT (0.649), FPG (0.660), and TyG (0.675) were all lower than this value. Time-dependent ROC analysis revealed that the AUC values of TyG-GGT remained stable between 0.7292-0.7338 over a prediction horizon of 1.0 to 5.0 years. The stability of these results was further corroborated via sensitivity analysis. Conclusion: This study found that TyG-GGT demonstrated an independent positive association and non-linear relationship with DM risk, with an inflection point at 380. TyG-GGT below 380 was associated with higher observed DM risk. Additionally, TyG-GGT exhibits discriminatory performance for DM risk assessment and may serve as a clinically useful predictor, thereby aiding clinicians in early identification of high-risk individuals and providing a novel perspective for optimizing clinical prevention and management of DM.