Metabolic Dysregulation in Acute Coronary Syndrome: The Link Between Diabetes and Insulin Resistance

Background: Metabolic dysregulation plays a crucial role in the pathogenesis and outcomes of acute coronary syndrome (ACS), yet the relationship between different metabolic phenotypes and cardiovascular outcomes remains incompletely understood. Objectives: This study aimed to investigate the association between metabolic status—ranging from insulin resistance to overt diabetes—and clinical outcomes in patients presenting with ACS, while exploring the underlying inflammatory and angiographic correlates. Methods: In this prospective observational study, 450 consecutive ACS patients were enrolled and categorized based on their metabolic status: known diabetes mellitus (DM), newly diagnosed DM, insulin resistance without DM, and metabolically healthy. Comprehensive metabolic profiling, inflammatory marker assessment, and detailed angiographic analysis were performed. Patients were followed for 12 months to evaluate major adverse cardiovascular events (MACE). Results: Of 450 patients (mean age 63.2±11.4 years, 64.9% male), 428 completed follow-up. The prevalence of known DM, newly diagnosed DM, and insulin resistance without DM was 41.3%, 21.8%, and 20.4%, respectively. Metabolically dysregulated patients demonstrated progressively higher SYNTAX scores (26.8±12.4 vs. 16.4±9.6, p<0.001) and inflammatory markers compared to metabolically healthy individuals. MACE rates at 12 months showed a significant gradient across metabolic phenotypes (28.0% in known DM, 24.5% in new DM, 16.3% in insulin resistance, 9.5% in metabolically healthy; p<0.001). After multivariate adjustment, known DM (HR 3.24, 95% CI 1.86-5.64), newly diagnosed DM (HR 2.68, 95% CI 1.48-4.86), and insulin resistance (HR 1.92, 95% CI 1.02-3.62) independently predicted MACE. Conclusions: Metabolic dysregulation exists along a continuum of cardiovascular risk in ACS patients, with both established and newly diagnosed diabetes, as well as insulin resistance, independently predicting adverse outcomes. These findings support comprehensive metabolic screening in ACS patients and suggest potential benefits of early metabolic intervention strategies.