Type 2 diabetes mellitus and incident carotid atherosclerosis: a retrospective cohort study on composite indices.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major global health challenge, with atherosclerotic cardiovascular disease (ASCVD) representing a leading cause of mortality. Carotid atherosclerosis (CAS), an early manifestation of ASCVD, can be assessed non-invasively via carotid ultrasonography. Composite indices derived from routine laboratory tests may offer comprehensive assessment of metabolic and inflammatory status, but systematic comparisons for predicting incident CAS in T2DM are limited. METHODS: This retrospective cohort study included 15,492 T2DM patients with ≥2 hospitalizations (2018-2024). Baseline was the first hospitalization; subsequent admissions served as follow-up. Seventeen composite indices were calculated from baseline laboratory data. Cox proportional-hazards regression with time-dependent coefficients was used as the primary analysis. Stratified and traditional Cox models were performed as sensitivity analyses. The Benjamini-Hochberg method was applied for multiple comparison correction. RESULTS: Over a median follow-up of 306.5 days, 1,841 patients (11.88%) developed CAS. In fully adjusted models, higher quartile levels of SII (HR = 1.38, P = 0.0046), SIRI (HR = 1.37, P = 0.0061), NLR (HR = 1.40, P = 0.0028), and NHR (HR = 1.34, P = 0.0115) were significantly associated with increased CAS risk. Albumin showed an inverse association (HR = 0.74, P = 0.0102). All associations remained significant after FDR correction (Q < 0.05). Age- and sex-stratified analyses suggested potential heterogeneity, though interactions were not significant. CONCLUSIONS: SII, SIRI, NLR, and NHR were independently associated with increased CAS risk in T2DM patients, while albumin was protective. These inflammation-based composite indices may aid in CAS risk stratification. However, findings should be considered exploratory due to the retrospective design; prospective validation is warranted.