Consequences of Hypoglycaemia on Cardiovascular and Inflammatory Responses in Patients With Diabetes Mellitus Type 1, Type 2 and Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Inflammatory responses of hypoglycaemia by measuring the cytokine production of isolated monocytes using ELISA
研究概览
简要总结
People with Type 1 diabetes (T1DM), type 2 diabetes (T2DM) and healthy volunteers will undergo a hypoglycaemic clamp to to investigate the effect of hypoglycaemia on cardiovascular and inflammatory responses.
详细描述
Objectives: The overall aim of the present study is to investigate the effect of hypoglycaemia on cardiovascular and inflammatory responses, molecular mechanisms and epigenetic profiles in various groups of people with diabetes type 1, type 2 and healthy volunteers.
Study design: Intervention study
Intervention: All subjects will undergo a hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (nadir 2.8 mmol/L), during and after which blood and urine will be sampled for further examination for up to one week.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
盲法说明
All subjects will undergo a hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (nadir 2.8 mmol/L), during and after which blood and urine will be sampled for further examination for up to one week.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •- 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
研究组 & 干预措施
T1DM poor glycaemic control
patients with type 1 diabetes and poor glycaemic control (HbA1c >8% / >64 mmol/mol will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
干预措施: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (Procedure)
T1DM impaired awareness
patients with type 1 diabetes and impaired awareness of hypoglycaemia will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
干预措施: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (Procedure)
T1DM Normal awareness
patients with type 1 diabetes and normal awareness of hypoglycaemia will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
干预措施: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (Procedure)
T2DM + Insulin
patients with type 2 diabetes with insulin treatment for at least 1 year will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
干预措施: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (Procedure)
Healthy control T2DM
healthy controls without diabetes and age, gender and BMI matched with diabetes type 2 participants will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
干预措施: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (Procedure)
Healthy control T1DM
Healthy controls without diabetes and age, gender and BMI matched with diabetes type 1 participants will undergo hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp
干预措施: hyperinsulinemic normoglycaemic-hypoglycaemic glucose clamp (Procedure)
结局指标
主要结局
Inflammatory responses of hypoglycaemia by measuring the cytokine production of isolated monocytes using ELISA
时间窗: 1.5 year
Cytokine production (TNF-alfa, IL-6, IL-10 and IL-1β) of isolated and stimulated monocytes
次要结局
- Epigenetic modifications(1.5 year)
- Metabolomics profile of each group(1.5 year)
- Cardiac function responses to hypoglycaemia using echocardiography(1.5 year)
- Oxidative stress responses using oxidative stress marker(1.5 year)
- Atherogenic responses of (recurrent) hypoglycaemia using foam cell formation.(1.5 year)
- Cognitive function responses to hypoglycaemia using cognitive function tests (TAP, PASAT)(1.5 year)