Real-life hypoglycaemia partially blunts the inflammatory response to experimental hypoglycaemia in people with type 1 diabetes

Aim: To determine whether recent repeated exposure to real-life hypoglycaemia affects the pro-inflammatory response during a hypoglycemia episode. Materials and Methods: This was a post hoc analysis of a hyperinsulinaemic normoglycaemic-hypoglycaemic clamp study, involving 40 participants with type 1 diabetes. Glucose levels 1 week before the clamp were monitored using a Freestyle Libre 1. Blood was drawn during normoglycaemia and hypoglycaemia, and 24 hours after resolution of hypoglycaemia for measurements of inflammatory responses and counterregulatory hormone levels. We determined the relationship between the frequency and duration of spontaneous hypoglycaemia, and time below range (TBR) and the inflammatory response to experimental hypoglycaemia. Results: On average, participants experienced 0.79 (0.43, 1.14) hypoglycaemia episodes per day, with a duration of 78 (47, 110) minutes and TBR of 5.5% (2.8%, 8.5%). TBR and hypoglycaemia frequency were inversely associated with the increase in circulating granulocyte and lymphocyte counts during experimental hypoglycaemia (P <.05 for all). A protein network consisting of DNER, IF-R, uPA, Flt3L, FGF-5 and TWEAK was negatively associated with hypoglycaemia frequency (P <.05), but not with the adrenaline response. Neither other counterregulatory hormones, nor hypoglycaemia awareness status, was associated with any of the inflammatory parameters markers. Conclusions: Repeated exposure to spontaneous hypoglycaemia is associated with blunted effects of subsequent experimental hypoglycaemia on circulating immune cells and the number of inflammatory proteins.