Ilyas F. Mustafajev¹, Marijn S. Hendriksz¹, Bastiaan E. de Galan¹, Rinke Stienstra¹, Cees J., Tack¹, Rick I. Meijer¹

1.Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

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Ilyas.Mustafajev@radboudumc.nl

Background: A controlled hypoglycaemic episode induces an inflammatory response, including an increased number of monocytes that is sustained for at least seven days. Although the underlying mechanism is unclear, we hypothesised the increase in adrenaline as counterregulatory response to be involved. Hence, we studied the effect of adrenaline on the increase in inflammatory cells in people with type 1 diabetes (T1DM) and controls without diabetes (CON).

Methods: Adults with T1DM and matched CON underwent adrenaline infusion at a rate of 0.04 µg/kg/min for 1 hour mimicking levels seen during hypoglycaemia. Blood was drawn at baseline (T0), after 30min (T30), 60min (T60), 180min (T180), 24hrs (T= +1day), 72hrs (T=+3days), and seven days (T=+7days) after start of adrenaline infusion. Immune cell composition of whole blood was measured using flowcytometry (Sysmex XN-450). Serial data were analysed with a mixed model analysis. The data are shown as mean±SD.

Results: Monocytes, our primary outcome, increased compared to baseline in both groups, peaking at T30; (from 0.54±0.17*10⁹/L to 0.87±0.18 *10⁹/L, P<0.001 and from 0.37±0.10*10⁹/L to 0.66±0.13*10⁹/L, P<0.001 in the T1DM and CON group, respectively). The changes from baseline (Fig) were not significantly different between the two groups across all timepoints. Similar findings were observed for lymphocytes and neutrophils.

Discussion/Conclusion: In the absence of hypoglycaemia, adrenaline elicits an acute rise in monocytes with restoration within 24 hours, which is similar in people with and without T1DM. A similar reaction was seen in lymphocytes and neutrophils. These data suggest that adrenaline drives the acute inflammatory response to hypoglycaemia.