Adrenaline is a prominent driver of inflammatory responses following hypoglycaemia

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.