Sensor-Detected Hypoglycaemia Is Associated With Inflammatory Protein and Immune Cell Alterations in People With Diabetes: Findings From the Hypo-METRICS Study.

AIMS: Experimental hypoglycaemia induces a persistent inflammatory response. We investigated whether real-life sensor-detected hypoglycaemia (SDH) is associated with immune parameters in people with Type 1 and Type 2 diabetes and explored potential differences between the groups. MATERIALS AND METHODS: In a multi-center observational study, 177 people with Type 1 diabetes and 185 with insulin-treated Type 2 diabetes were recruited to wear blinded glucose sensors for 10 weeks. SDH metrics derived from these sensors included SDH frequency, SDH duration, and time below range (TBR). At the end of the observation period, fasting blood was drawn to measure levels of circulating inflammatory proteins (Type 1 n = 177, Type 2 n = 185), ex vivo monocyte function (Type 1 n = 59; Type 2 n = 90), and circulating immune cell counts (Type 1 n = 29; Type 2 n = 87). RESULTS: Four circulating inflammatory proteins (CCL28, CX3CL1, IL-17A, IL-17C) were positively associated with SDH frequency, SDH duration and TBR in both groups (all p < 0.05). In Type 1 diabetes, pro-inflammatory responses of monocytes to pathogenic stimuli were inversely associated with SDH frequency, SDH duration and TBR, particularly Pam3Cys-induced IL-6 production (all p < 0.05); similar but less pronounced associations were observed in Type 2 diabetes. SDH frequency and TBR were inversely associated with total circulating immune cell, neutrophil and monocyte counts in Type 1 diabetes (all p < 0.05). CONCLUSIONS: Exposure to real-life hypoglycaemia is associated with immune alterations in people with Type 1 and Type 2 diabetes, including increased levels of circulating inflammatory proteins in both diabetes types and reduced monocyte function and immune cell counts, particularly in Type 1 diabetes. TRIAL REGISTRATION: NCT04304963.