γδ T-cell interferon-γ production reflects metabolic improvement during SGLT2 inhibitor-based therapy in type 2 diabetes
Abstract
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+ and Vδ2+ γδ T-cell subsets compared with controls, while subset frequencies remained unchanged. During follow-up, successful antidiabetic therapy was associated with a progressive reduction in IFN-γ production, reaching approximately 40% after 12 months (p<0.01). This reduction did not correlate with changes in HbA1c and was not enhanced by the addition of GLP-1 receptor agonist therapy. In contrast, lower IFN-γ production was associated with improved insulin sensitivity, reduced fat mass, and markers of improved metabolic…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 30 participants or records.
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