Metabolic Adaptation to High-frequent Hypoglycaemia in Type 1 Diabetes - the HypoADAPT Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Glycogen in muscle and adipose tissue
研究概览
简要总结
An experimental mechanistic study. The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. The knowledge to be obtained may feed into experimental hypoglycaemic clamp studies to further elucidate the effect of the adaptations during acute hypoglycaemia. Ultimately, it may lead to intervention studies aiming at the maintenance of functional capability during hypoglycaemia in patients with type 1 diabetes to reduce their risk of severe hypoglycaemia.
详细描述
Study rationale The risk of severe hypoglycaemia is a major daily concern for people with diabetes treated with insulin. Severe hypoglycaemia is the main barrier in achieving the recommended glycaemic targets and may indirectly be the main driver for late diabetic complications and related morbidity, mortality and health care costs. In people with diabetes, recurrent exposure to insulin-induced mild hypoglycaemia leads to significant adaptive physiologic responses. While the metabolism of the brain and hormonal responses to hypoglycaemia have been studied extensively, this study will as the first, systematically investigate the chronic adaptation of peripheral metabolism to recurrent hypoglycaemia in diabetes. Knowledge about such responses can lead to interventions that attenuate the devastating effects of acute hypoglycaemia induced by insulin in people with diabetes. Thereby, the risk of developing severe hypoglycaemia can be reduced which ultimately will improve long-term diabetes outcomes and reduce health care costs.
Hypothesis Patients with type 1 diabetes that are exposed to high-frequent recurrent hypoglycaemia will adapt their metabolism in a way, which supports the preservation of brain fuelling.
Objectives
Primary objective The overall objective is to gain new knowledge about mechanisms involved in adaptation to recurrent hypoglycaemia in diabetes by investigating patients with type 1 diabetes and healthy controls. The knowledge to be obtained may feed into experimental hypoglycaemic clamp studies to further elucidate the effect of the adaptations during acute hypoglycaemia. Ultimately, it can lead to intervention studies aiming at the maintenance of functional capability during hypoglycaemia in patients with type 1 diabetes to reduce their risk of severe hypoglycaemia.
Secondary objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability to provide written informed consent
- •Male or female aged 18-70 years
- •Must be able to speak and read Danish
- •Type 1 diabetes patients or healthy individuals (control goup)
- •A documented clinically relevant history of type 1 diabetes
- •In insulin treatment regimen
- •The subject must be willing and able to comply with trial protocol
排除标准
- •History of severe psychological condition
- •History of severe heart disease
- •History of epilepsy, former apoplexies and dementia
- •History of muscle diseases
- •History of liver disease
- •History of malignancy unless a disease-free period exceeding 5 years
- •Implants not compatible for MRI scans
- •History of alcohol or drug abuse
- •Pregnant or lactating woman
研究组 & 干预措施
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: insulin human (Drug)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Epinephrin (Drug)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Muscle biopsy (Procedure)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Adipose tissue biopsy (Procedure)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Glucagon (Drug)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: IPRO 2 Medtronic Minimed (Device)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: 7 Tesla (7T) Magnetic Resonance Imaging (Procedure)
Healthy Controls
Healthy Controls
干预措施: Glucagon (Drug)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Indirect Calorimetry using Jaeger Oxycon Champion (Procedure)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Core temperature and thermography using Thermovision SC645 (Procedure)
Participants with Type 1 Diabetes Mellitus
Participants with Type 1 Diabetes Mellitus
干预措施: Freestyle Libre 2 (Device)
Healthy Controls
Healthy Controls
干预措施: insulin human (Drug)
Healthy Controls
Healthy Controls
干预措施: Epinephrin (Drug)
Healthy Controls
Healthy Controls
干预措施: Muscle biopsy (Procedure)
Healthy Controls
Healthy Controls
干预措施: Adipose tissue biopsy (Procedure)
Healthy Controls
Healthy Controls
干预措施: IPRO 2 Medtronic Minimed (Device)
Healthy Controls
Healthy Controls
干预措施: 7 Tesla (7T) Magnetic Resonance Imaging (Procedure)
Healthy Controls
Healthy Controls
干预措施: Indirect Calorimetry using Jaeger Oxycon Champion (Procedure)
Healthy Controls
Healthy Controls
干预措施: Core temperature and thermography using Thermovision SC645 (Procedure)
结局指标
主要结局
Glycogen in muscle and adipose tissue
时间窗: 5 minutes
Glycogen in muscle and adipose tissue biopsies during euglycaemia
Brain adenosine triphosphate (ATP) concentration
时间窗: 20 minutes
Brain ATP concentration using non-invasive MR spectroscopy during euglycaemia
Glycogen concentration
时间窗: 40 minutes
Glycogen in liver and muscle tissue using non-invasive MR spectroscopy during euglycaemia.
Metabolite- and lipid profiling
时间窗: 5 minutes
Metabolite- and lipid profiling of blood samples using metabolomics profiling platforms during euglycaemia
Brain lactate concentration
时间窗: 20 minutes
Brain lactate concentration using non-invasive magnetic resonance (MR) spectroscopy during euglycaemia
Non-specific proteins in muscle and adipose tissue
时间窗: 5 minutes
Non-specific proteins in muscle and adipose tissue biopsies during euglycaemia
次要结局
- Plasma free fatty acids during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Estimated glucose production during glucagon stimulation(Every 5 minutes up to 5 hours)
- Plasma norepinephrine during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Plasma lactate during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Plasma epinephrine during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Indirect calorimetry(60 minutes)
- Plasma metabolomics during glucagon injections.(Every 40 minutes up to 5 hours)
- Plasma alanine during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Plasma β-hydroxybutyrate during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Plasma insulin during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Plasma metabolomics during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Personality traits using the psychometry questionnaire Type D Scale-14 (DS-14)(30 minutes)
- Diabetes and hypoglycaemia status using psychometry questionnaire Problem Areas in Diabetes (PAID)(30 minutes)
- Food consumption(30 minutes)
- Plasma lactate during glucagon injections.(Every 40 minutes up to 5 hours)
- Plasma free fatty acids during glucagon injections.(Every 40 minutes up to 5 hours)
- Plasma glycerol during glucagon injections.(Every 40 minutes up to 5 hours)
- Plasma alanine during glucagon injections.(Every 40 minutes up to 5 hours)
- Plasma insulin during glucagon injections.(Every 40 minutes up to 5 hours)
- Plasma glycerol during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Plasma glucagon during epinephrine infusion(Every 20 minutes up to 90 minutes)
- Hypoglycemia awareness status(10 minutes)
- Estimated glucose production during epinephrine stimulation(Every 5 minutes up to 90 minutes)
- Thermography(5 minutes)
- Plasma β-hydroxybutyrate during glucagon injections.(Every 40 minutes up to 5 hours)
- Personality traits using the psychometry questionnaire Toronto Alexithymia Scale (TAS-20)(30 minutes)
- Diabetes and hypoglycaemia status using psychometry questionnaire Hypoglycemia Fear Survey - Worry (HFS-W)(30 minutes)
- Diabetes and hypoglycaemia status using psychometry questionnaire Hypoglycemia Attitudes and Behavior Scale (HABS)(30 minutes)
- Plasma glucagon during glucagon injections.(Every 40 minutes up to 5 hours)