Adrenaline is a prominent driver of inflammatory responses following hypoglycaemia

Abstract Aims/hypothesis Hypoglycaemia induces an acute and sustained inflammatory response both in people with type 1 diabetes and in people without diabetes. To investigate the role of adrenaline (epinephrine) in this response, we measured the inflammatory effects of adrenaline in a concentration and timeframe comparable to that seen during hypoglycaemia, in people with type 1 diabetes and matched control participants without diabetes. Methods Adults with type 1 diabetes and matched control participants received adrenaline intravenously at 0.04 µg kg −1 min −1 for 1 h. Blood was drawn at baseline, after 30, 60 and 180 min, and on days 1, 3 and 7 following start of adrenaline administration, to determine white blood cell counts, cytokine secretion using ex vivo stimulation of isolated monocytes and circulating inflammatory markers using the Olink inflammatory panel. Results Adrenaline acutely increased neutrophil, lymphocyte and monocyte counts in both groups. While neutrophil and monocyte levels returned to baseline after 1 day, lymphocytes remained elevated for 7 days. Adrenaline acutely altered monocyte function towards a more inflammatory phenotype, reflected by increased secretion of cytokines after ex vivo stimulation with lipopolysaccharide in both groups. Adrenaline also increased circulating inflammatory proteins, including urokinase-type plasminogen activator, Fms-like tyrosine kinase 3 ligand, chemokine (C-X3-C motif) ligand 1 and fibroblast growth factor 21, after 7 days in both groups, with a more pronounced response in people with type 1 diabetes. Conclusions/interpretation Levels of adrenaline similar to those seen in response to hypoglycaemia elicit an acute and prolonged inflammatory response in people with type 1 diabetes and matched control participants on a cellular, functional and protein level. These findings suggest that adrenaline is a prominent driver of inflammatory responses following hypoglycaemia. Trial registration ClinicalTrials.gov NCT05990933 Graphical Abstract