| Outcome Measures: |
Primary: Monocyte count after 60 minutes of hypoglycaemia and adrenergic blockade, The number of monocytes following 60 minutes hypoglycaemia and adrenergic blockade compared to baseline. Adrenergic blockade using Phentolamine and Propranolol intravenously. Expressed in 10\^3/µl measured using a sysmex machine., After 60 minutes of hypoglycaemia and adrenergic blockade | Secondary: Leukocyte count at the time points, Leukocyte count at the time points 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia, +1 day, +3 days and 1 week after of hypoglycaemia (e.g. Monocytes, granulocytes, lymphocytes)., 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia, +1 day, +3 days and 1 week after of hypoglycaemia|Ex vivo production of pro- and anti-inflammatory cytokines and chemokines, Ex vivo production of pro- and anti-inflammatory cytokines and chemokines after ex vivo stimulation of isolated leukocytes, including Tumor necrosis factor-α, Interleukin-6, Interleukin-10 and Interleukin-1β, 1β, 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia, +1 day, +3 days and 1 week after of hypoglycaemia|92 circulating inflammatory proteins, 92 circulating inflammatory proteins using Olink Proteomics inflammation panel, 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Inflammatory plasma protein ( e.g. high-sensitive crp), Inflammatory plasma protein using ELISA,(e.g high sensitive-crp), 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Atherogenic parameters, Atherogenic parameters using ELISA including but not limited to, vascular endothelial cell adhesion molecule-1, vascular endothelial cell adhesion molecule-1, E-Selectin, P-selectin, Plasminogen activator inhibitor-1, Plasma Endothelin, 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Plasma levels of hormones, Plasma levels of hormones ( Cortisol, insulin, glucagon, growth-hormone, adrenaline, noradrenaline), 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Amount of hypoglycaemic events measured by the blinded continuous glucose monitor, Amount of events, During the full study, 3 days before and 7 days after each investigational day|Variability measured by the blinded continuous glucose monitor, Variability of glucose expressed as a standard deviation of the mean glucose, During the full study, 3 days before and 7 days after each investigational day|Average glucose measured by the blinded continuous glucose monitor, Average glucose during the 10 days of measuring expressed as mmol/L, During the full study, 3 days before and 7 days after each investigational day|Time in range measured by the blinded continuous glucose monitor, Amount of time that glucose is between 3.8 and 10 mmol/L expressed as a percentage, During the full study, 3 days before and 7 days after each investigational day|Amount of plasma glycerol, Amount of plasma glycerol during and after hypoglycaemia, 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Amount of Non-esterified fatty acids, Amount of Non-esterified fatty acids (NEFAs) during and after hypoglycaemia, 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Untargeted metabolomics profiling, Measuring a panel of amino acids, 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Gene expression changes in leukocytes, Gene expression changes in leukocytes (e.g. using RNA sequencing, quantitative PCR), 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Epigenetic changes in leukocytes, Epigenetic changes in leukocytes (e.g. using Assay for Transposase- Accessible Chromatin using sequencing (ATACseq), DNA methylation analysis), 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Functional changes in monocytes, Functional changes in monocytes (e.g. using adhesion assays, differentiation experiments), 0, 30 minutes after euglycaemia, 60 minutes during hypoglycaemia|Adrenergic symptoms assessed using the validated Edinburgh Hypoglycaemia Score, 0, 30 minutes after euglycaemia, 30 minutes and 60 minutes during hypoglycaemia|Hypoglycaemia awareness using the modified Clarke score, At screening | Other: HbA1c expressed in mmol/L, At screening|Serum creatinine for kidney function expressed in umol/L, Once at the screening at least 1 week before the hypoglycaemia|Vitals ( blood pressure and heart rate), Measured by automatic sphygmomanometer, At both investigational days, every 15 minutes during each investigational day for a total of 8 hours.|Body mass index, Using length and weight expressed in kg/m\^2, Once at the screening at least 1 week before the hypoglycaemia|Age, Once at the screening at least 1 week before the hypoglycaemia|Sex, Male or female, Once at the screening at least 1 week before the hypoglycaemia|Duration of diabetes ( years), Once at the screening at least 1 week before the hypoglycaemia
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