Limited impact of impaired awareness of hypoglycaemia and severe hypoglycaemia on the inflammatory profile of people with type 1 diabetes

Aim To investigate whether a history of severe hypoglycaemia (SH) or the associated presence of impaired awareness of hypoglycaemia (IAH) is characterized by a pro-inflammatory profile in people with type 1 diabetes. Research design and methods We measured circulating inflammatory markers and pro- and anti-inflammatory cytokine production afterex vivostimulation of peripheral blood mononuclear cells (PBMCs) in a well-characterized cohort of individuals with type 1 diabetes (n = 239) and in people without diabetes (n = 56). Data were corrected for confounders by using multivariate linear regression models. Results People with type 1 diabetes had higher circulating concentrations of high-sensitivity C-reactive protein (hs-CRP; 0.91 [0.36-2.25] vs. 0.52 [0.20-0.98] pg/mL,P <0.001 and interleukin-18-binding protein (IL-18BP; 1746 [1304-2112] vs. 1381 [1191-1807] pg/mL;P =0.001) than those without diabetes. In multivariate analysis, only higher hs-CRP concentrations persisted. Neither circulating immune cells norex vivocytokine levels produced by PBMCs in response to an extensive panel of stimuli differed in groups defined by awareness state or a history of SH, apart from elevated IL-18BP in people with, versus those without, history of SH (1524 [1227-1903] vs. 1913 [1459-2408] pg/mL;P <0.001). Conclusions IAH or history of SH in people with type 1 diabetes was not associated with altered inflammatory profiles, arguing against chronically elevated inflammatory activity mediating the increased cardiovascular risk associated with hypoglycaemia. The finding of higher circulating concentrations of IL-18BP in individuals with a history of SH requires further investigation.