Association of Systemic Inflammatory and Metabolic Biomarkers with Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes: A Prospective Cohort Study
TL;DR
A combined inflammatory–metabolic profile identified patients with T2DM who experienced subsequent cardiovascular events and may provide complementary information when used alongside standard cardiovascular risk assessment.
Abstract
Background: Cardiovascular complications continue to occur in type 2 diabetes mellitus (T2DM) despite treatment of established risk factors. Biomarkers reflecting immune activation and metabolic disturbance may reveal clinically relevant residual risk. Objective: To examine whether routinely obtainable inflammatory and metabolic indices are related to subsequent major adverse cardiovascular events (MACE) in adults with T2DM. Methods: We prospectively followed 120 adults with established T2DM at Rashid Latif Khan University Medical College, Lahore, Pakistan, from June 2025 to April 2026. Baseline testing comprised high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), glycated hemoglobin (HbA1c), lipid measures, and the triglyceride-glucose (TyG) index. The prespecified composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke. Time-to-event associations were estimated with Cox regression, and predictive discrimination was explored using receiver-operating characteristic analysis. Results: Twenty-four participants (20.0%) reached the composite endpoint. Event-positive participants had less favorable inflammatory and metabolic profiles, characterized by higher hs-CRP, NLR, SII, HbA1c, triglycerides, and TyG index and lower HDL-C. After covariate adjustment, hs-CRP (aHR 1.13 per 1 mg/L), SII (aHR 1.09 per 100 units), HbA1c (aHR 1.29 per 1%), and TyG index (aHR 1.71 per unit) remained associated with MACE. Their combined model yielded an AUC of 0.86, with 83.3% sensitivity and 78.1% specificity. Conclusion: A combined inflammatory–metabolic profile identified patients with T2DM who experienced subsequent cardiovascular events. hs-CRP, SII, HbA1c, and TyG index may provide complementary information when used alongside standard cardiovascular risk assessment.