Consequences of Hypoglycaemia on Cardiovascular and Inflammatory Responses

Inclusion Criteria: Overall inclusion criteria * Ability to provide written informed consent * Must be able to speak and read Danish (for Hillerød-site) and Dutch (for Nijmegen-site) * Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump) (except for group 5) * Body-Mass Index: 19-40 kg/m2 * Age ≥18 years, ≤ 80 years * Blood pressure: \<140/90 mmHg * Duration of diabetes \> 1 year (except for group 5) * HbA1c \< 100 mmol/mol Group specific * Group 1: HbA1c \>64 mmol/mol * Group 2: impaired awareness of hypoglycaemia (IAH) as assessed by a score of ≥3 on the modified Clarke questionnaire, ≥4 on the Gold questionnaire and a positive score on the Pedersen-Bjergaard questionnaire. * Group 3: normal awareness of hypoglycaemia (NAH) as assessed by a score of \<3 on the modified Clarke questionnaire, \<4 on the Gold questionnaire and a negative score on the Pedersen-Bjergaard. * Group 4: Insulin treatment for at least 1 year * Group 5/6: HbA1c \<42 mmol/mol Exclusion Criteria: * \- Severe medical or psychological conditions interfering with the perception of hypoglycaemia other than IAH such as brain injuries, epilepsy, a major cardiovascular disease event or anxiety disorders * Use of immune-modifying drugs or antibiotics * Treatment with glucose-modifying (other than insulin, SGLT-2 inhibitors and metformin) agents (e.g. prednisolon) * Use of anti-depressive drugs * Pregnancy or breastfeeding or unwillingness to undertake measures for birth control * Use of statins (e.g. stop statins \>2 weeks before performing blood sampling. This can be safely done in the context of primary prevention) * Any event of cardiovascular disease in the past 5 years (e.g. myocardial infarction, stroke, heart failure, symptomatic peripheral arterial disease) * Auto-inflammatory or auto-immune diseases * Any infection in past three months * Previous vaccination in the past three months * Laser coagulation for proliferative retinopathy in the past six months * Proliferative retinopathy * Diabetic nephropathy as reflected by an albumin-creatinine ratio ˃ 30 mg/gor an estimated glomerular filtration rate (by MDRD) ˂60ml/min/1.73m2 * History of pancreatitis (acute or chronic) or pancreatic cancer