Imbalance of T cell subsets: a core event that mediates the progression of T2DM and its complications.

Type 2 diabetes mellitus poses a substantial global health burden, increasing evidence highlights the critical role of T cells in promoting T2DM progression. This review provides an overview of the mechanisms by which specific T cell subsets drive T2DM pathogenesis and its complications, while also highlighting emerging immunotherapeutic strategies. Preceding overt T2DM, T cells infiltrate insulin-sensitive tissues early, and a skewing of T cell subsets toward pro-inflammatory phenotypes leads to an imbalance that fosters inflammation and M1 macrophage polarization, driving the development of T2DM. In addition, this T cell subset imbalance contributes to disease progression by inducing insulin resistance and β-cell dysfunction. As T2DM progresses, the T cell subset imbalance and their tissue infiltration extend to the cardiovascular system, kidneys, retina, brain, and peripheral tissues-contributing to diabetic complications such as atherosclerosis, diabetic kidney disease, diabetic retinopathy, Alzheimer's disease, and diabetic foot ulcers. The evidence summarized in this review underscores the central role of T cell subset imbalance in the progression of T2DM and its associated complications. Building on these findings, we also examine both established and emerging therapeutic strategies, including restoring T cell subset balance, modulating T cell-derived pro- and anti-inflammatory cytokines, and shifting macrophage polarization driven by pro-inflammatory T cells, to offer critical insights for future clinical intervention. T cell subset imbalance is a core driver of the progression of T2DM and its complications, and targeting T cell dysregulation represents a promising frontier in T2DM therapy.