Senescent T cells predict the development of hyperglycemia in humans

Senescent T cells have been implicated in chronic inflammatory and cardiovascular diseases. In this study, we explored the relationship between senescent T cells and glycemic status in a cohort of 805 participants by investigating the frequency of CD57⁺ or CD28^null senescent T cells in peripheral blood. Participants with normal glucose tolerance (NGT) with follow-up data (N = 149) were included to determine whether hyperglycemia (prediabetes or type 2 diabetes) developed during followup (mean 2.3 years). CD8⁺CD57⁺ and CD8⁺CD28^null T-cell frequencies were significantly higher in prediabetes and type 2 diabetes compared with NGT. Increased CD57⁺ or CD28^null cells in the CD8⁺ T-cell subset were independently associated with hyperglycemia. Furthermore, among participants with baseline NGT, the frequency of CD8⁺CD57⁺ T cells was an independent predictor of hyperglycemia development. Immunofluorescent analyses confirmed that CD8⁺CD57⁺ T-cell infiltration was increased in visceral adipose tissue of patients with prediabetes or type 2 diabetes compared with those with NGT. Our data suggest that increased frequency of senescent CD8⁺ T cells in the peripheral blood is associated with development of hyperglycemia.