High glycaemic variability in individuals with type 1 diabetes is associated with a reduced proportion of CD8+ TNF+ cells in response to influenza A virus

ObjectiveDiabetes 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. In healthy individuals, blood glucose levels remain relatively stable throughout the day. However, in individuals living with diabetes, blood glucose spikes are more frequent and higher in magnitude. Continuous glucose monitoring (CGM) provides a unique opportunity to detect these hyper and hypoglycaemic events, even in the presence of an in range HbA1c. Research design and methodsHere, we use blood samples and CGM data obtained from people living with Type 1 diabetes (T1D) to determine the effects of glycaemic variability on the T-cell response to influenza virus. Low glycaemic variability was defined as a coefficient of variation (CV) <33% (n = 13) whilst high glycaemic variability was defined as a CV >33% (n = 19). ResultsWe show that high glycaemic variability in participants living with T1D is associated with a reduced proportion of CD8+CD107-IFN{gamma}-MIP1{beta}-TNF+ T-cells in response to stimulation with influenza virus and an influenza peptide pool. High glycaemic variability in this patient population is primarily driven by hypoglycaemic events and was also associated with an increase in the proportion of naive CD8+ T cells and a decrease in terminally differentiated CD8+ T cells (TEMRA). ConclusionsTogether, this study provides the first evidence that glycaemic variability affects the 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.