γδ T-cell interferon-γ production reflects metabolic improvement during SGLT2 inhibitor-based therapy in type 2 diabetes.

Introduction: Chronic low-grade meta-inflammation contributes to insulin resistance and metabolic dysfunction in type 2 diabetes (T2D). γδ T cells have emerged as important mediators of metabolic inflammation, yet their responsiveness to metabolic improvement in humans remains poorly understood. We investigated whether successful antidiabetic therapy is associated with alterations in γδ T cell-mediated inflammation in patients with T2D. Methods: Twenty-five patients with poorly controlled T2D initiating SGLT2i therapy (n=15) or SGLT2i plus GLP-1RA (n=10) were prospectively followed for 12 months. Age- and sex-matched non-diabetic controls (n=30) were included at baseline. Peripheral blood γδ T cell phenotype and cytokine production were assessed by multiparametric flow cytometry. Metabolic, hepatic, and renal parameters were evaluated longitudinally. Results: At baseline, patients with T2D exhibited increased interferon-γ (IFN-γ) production by both Vδ1 Discussion: This real-world study shows that γδ T cell-mediated meta-inflammation decreases during successful antidiabetic therapy independently of glycemic control. IFN-γ production by γδ T cells is closely associated with insulin resistance, adiposity, and metabolic organ dysfunction, supporting its potential utility as a biomarker of metabolic tissue stress and therapeutic response in T2D.