Activated CD8⁺HLA-DR⁺ T Cells as Immune Biomarkers of Metabolic Dysfunction and Cardiovascular Risk in Prediabetes

Background Prediabetes is characterized by metabolic dysfunction and chronic low-grade inflammation, both of which contribute to β-cell impairment and elevated cardiovascular risk. While activated CD8⁺ T cells expressing HLA-DR (CD8⁺HLA-DR⁺) have been implicated in obesity-related inflammation, their role in prediabetes remains undefined. Methods In this cross-sectional study, overweight and obese adults (BMI ≥ 25 kg/m²) were stratified into three groups: lean healthy (LH), metabolically healthy overweight/obese (HO), and prediabetic overweight/obese (Pre-OB). Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify CD8⁺HLA-DR⁺ T cells. Circulating cytokines and metabolic markers, including fasting glucose, insulin, C-peptide, lipid profiles, and β-cell function (HOMA-B%), were measured. Correlations with cardiovascular risk markers were evaluated. Results The frequency of CD8⁺HLA-DR⁺ T cells was significantly higher in Pre-OB individuals compared to HO and LH groups (p < 0.001). These cells positively correlated with fasting C-peptide (r = 0.32, p = 0.03) and inversely with HOMA-B% (r = − 0.35, p = 0.02), indicating a link with β-cell dysfunction. CD8⁺HLA-DR⁺ T cells also correlated with inflammatory cytokines (IL-6, TNF-α, IFN-γ) and cardiovascular risk markers including diastolic blood pressure, triglycerides, and MMP-9 (all p < 0.05). Conclusions Activated CD8⁺HLA-DR⁺ T cells are significantly enriched in obese individuals with prediabetes and are associated with markers of β-cell dysfunction, systemic inflammation, and cardiovascular risk. These findings identify CD8⁺HLA-DR⁺ T cells as potential immune biomarkers for early cardiometabolic deterioration and targets for preventative strategies in high-risk prediabetic populations.