Metabolic hallmarks of type 2 diabetes compromise T cell function

Type 2 diabetes (T2D) manifests as profound systemic metabolic dysregulation. Mounting evidence indicates T2D significantly impairs T cell immunity, compromising both protective immune responses and immune homeostasis. This dysfunction stems from the multitude roles of metabolites in T cell biology: energy substrates, signaling molecules, and epigenetic regulators. In this review, we synthesize current evidence on how the metabolic hallmarks of T2D (hyperglycemia, hyperinsulinemia, and dyslipidemia) reprogram T cell metabolism and their functionalities. Notably, most patients with T2D receive combination antidiabetic therapies which not only correct systemic metabolism but also exert direct immunomodulatory effects on T cells. Unraveling the interplay between disease-driven metabolic perturbations and pharmacologically induced immunomodulation is essential to advance therapeutic strategies that restore immune competence while preserving immunoregulatory balance.