Association between the composite CRP-TyG index and incident malignancy risk in hospitalized patients with diabetes: a retrospective cohort study with nonlinear effect analysis.

Background: Diabetes mellitus is increasingly recognized as a risk factor for malignancy, partly through chronic low-grade inflammation and insulin resistance. The composite C-reactive protein-triglyceride glucose (CRP-TyG) index integrates inflammatory and metabolic dimensions and may therefore provide a more informative marker for cancer risk stratification than either component alone, particularly in hospitalized patients with diabetes. However, its association with incident malignancy and its potential nonlinear pattern have not been well characterized in this population. Methods: This retrospective cohort study included 5,500 adult inpatients with diabetes between 2014 and 2025. The CRP-TyG composite index was calculated using standardized laboratory measurements obtained within 24-48 hours of admission. Incident malignancies were identified primarily through pathology-confirmed diagnoses and tumor registry records, with diagnostic coding used as supplementary evidence when necessary. Associations between the CRP-TyG index and malignancy risk were evaluated using multivariable Cox proportional hazards models, restricted cubic spline analyses for nonlinear dose-response assessment, and segmented regression to identify threshold effects. Stepwise covariate adjustment, subgroup analyses, landmark analyses, and additional sensitivity analyses were performed to test the robustness of the findings. Results: During follow-up, 344 incident malignancies were documented. Malignancy risk increased progressively across CRP-TyG quartiles, with the highest quartile showing a significantly elevated risk compared with the lowest quartile in the fully adjusted model (HR = 1.92, 95% CI: 1.42-2.60; P for trend < 0.001). A significant nonlinear association was observed, with an inflection point at a CRP-TyG z-score of 0.62, above which the risk increased more steeply. Compared with CRP or TyG alone, the composite index showed better discriminatory performance and demonstrated the strongest association with gastrointestinal cancers. The overall findings remained directionally consistent across subgroup and landmark analyses. Conclusions: The CRP-TyG composite index was independently associated with a higher risk of incident malignancy in hospitalized patients with diabetes and showed a clear nonlinear dose-response pattern. As a simple biomarker derived from routine laboratory tests, it may help support early malignancy risk stratification in this high-risk population.