Atherogenic Lipid Indices in Colorectal Cancer: Metabolic Associations and Survival Outcomes

Background/Objectives: Type 2 diabetes mellitus (T2DM) and atherogenic dyslipidemia have been implicated in colorectal cancer (CRC) development, but their prognostic relevance after cancer diagnosis remains unclear. This study aimed to evaluate the association between T2DM, lipid-derived atherogenic indices, and survival outcomes in patients with CRC. Methods: We conducted a retrospective cohort study including 240 CRC patients, of whom 60 had coexisting T2DM. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier (KM) method and log-rank tests. In the absence of recurrence-specific data, DFS was defined as time to death or last follow-up. Lipid-related indices, including the atherogenic index of plasma (AIP), atherogenic coefficient (AC), remnant cholesterol (RC), non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride-glucose (TyG) index, and triglyceride-to-HDL cholesterol ratio (TG/HDL-C), were evaluated by tertiles in KM analyses. Multivariable Cox proportional hazards models were constructed to assess the independent prognostic value of AIP, AC, and RC (entered separately as a continuous variable standardized to 1 standard deviation), adjusted for age, sex, adjuvant chemotherapy, radiotherapy, and T2DM status. Sensitivity analyses were performed in stage III-IV patients. Results: During follow-up, 28 deaths occurred. OS did not differ significantly between CRC patients and those with CRC coexisting with T2DM (log-rank p-values = 0.220). DFS analyses showed no significant differences across tertiles of any lipid-related index (all log-rank p-values > 0.05), with overlapping survival curves and no consistent dose-response patterns. In adjusted Cox models, AIP (hazard ratio [HR] per 1 SD = 0.71, 95% CI 0.48-1.06), AC (HR = 0.72, 95% CI 0.44-1.20), and RC (HR = 0.66, 95% CI 0.39-1.12) were not independently associated with DFS. Results were consistent in advanced-stage disease (stage III-IV). Conclusions: In this cohort of patients with CRC, neither T2DM nor lipid-derived indices reflecting atherogenic dyslipidemia and insulin resistance were independently associated with OS or DFS. These findings help refine the clinical interpretation of lipid-derived biomarkers in CRC, suggesting limited prognostic utility beyond established oncologic factors.