High glycaemic variability is associated with a reduced T cell cytokine response to influenza A virus

Diabetes mellitus significantly increases the risk of severe respiratory virus disease like influenza and COVID-19. Early evidence suggests that this susceptibility to respiratory viral disease is driven by glycaemic variability, rather than average blood glucose levels. Here, we use blood samples and constant glucose monitoring (CGM) data obtained from people living with Type 1 diabetes (T1D) to determine the effects of glycaemic variability on the ex vivo T-cell response to influenza virus. We show that high glycaemic variability in participants living with T1D is associated with a reduced proportion of CD8+CD107α-IFNγ-MIP1β-TNF+ T-cells in response to stimulation with influenza virus and an influenza peptide pool. Thus, this study provides evidence that glycaemic variability affects the ex vivo T-cell response to respiratory viruses. These data suggest that monitoring glycaemic variability may have important implications in understanding the antiviral immune response in people with diabetes.