Metabolic and Central Nervous System Characterisation of the Phenotype of Non-suppressed (Rising) Glucagon After Glucose Challenge
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Brain activity
研究概览
简要总结
The investigators previously characterized a phenotype with non-suppressed glucagon at 120 minutes after standardized oral glucose load. This phenotype is associated with healthy metabolic traits such as lower BMI, higher insulin sensitivity and lower liver fat content. Glucagon is a pleiotropic hormone that, besides its main action on increasing endogenous glucose production, also reduces appetite and increases basal energy expenditure. The aims of this study are to i. detect functional differences in the appetite-related central nervous system (CNS) areas between the suppressed and non-suppressed glucagon phenotype ii. mimick the non-suppressed glucagon phenotype in those participants who suppress glucagon by administering a very-low-dose glucagon infusion and retest them.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
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
- •BMI 18.5- 29.9 kg/m2
- •written informed consent
排除标准
- •febrile infection with temperatures> 38.5 ° C in the last 14 days
- •Blood donation within the last 12 weeks Pre-study Inclusion
- •Chronic diseases:
- •Diabetes mellitus
- •Known liver diseases (hepatitisB/C, hemochromatosis, NASH)
- •Chronic inflammatory diseases (rheumatoid arthritis, Crohn's disease, ulcerative colitis) chronic renal insufficiency
- •Cancer (known malignant disease)
- •psychiatric diagnoses (bipolar disorder, schizophrenia, psychoses, depression, agoraphobia)
- •Persons with non-removable metal parts, e.g:
- •pacemaker
- •artificial heart valves
- •metal prostheses
- •implanted magnetic metal parts (screws, plates of operations)
- •metal slivers / garnet splinters
- •fixed braces
- •Acupuncture needle
- •Insulin pump
- •totally implantable venous access device (port)
- •tattoos, metallic eye shadows
- •Persons with impaired sensitivity and / or increased sensitivity to heating of the body
- •Medical history of venous thromboembolism
- •alcohol consumption of more than 50g / day
- •In physical examination:
- •blood pressure > 160/100 mmHg pathologic cardiac murmurs (diastolic or systolic louder than 2/6)
- •in the blood test: fasting glucose ≥ 125 mg/dl or HbA1c ≥ 6.5% AST or ALT> 2.5x upper limit of the reference range (> 125 U/l) Hb <12 g/dl C reactive protein (CRP) > 5 mg / dL or leukocytes> 15000/μl
研究组 & 干预措施
Intravenous glucagon
Low-dose glucagon infusion (0.5 pmol/min/kg body weight) over 150 minutes during a standardized 75 g oral glucose tolerance test
干预措施: Intravenous glucagon (Drug)
Intravenous saline
Saline infusion over 150 minutes during a standardized 75 g oral glucose tolerance test
干预措施: Intravenous saline (Drug)
结局指标
主要结局
Brain activity
时间窗: change from baseline to 120 minutes after oral glucose challenge
Resting-state brain activity assessed by fMRI
次要结局
- Basal energy expenditure(150 minutes after oral glucose challenge)
- Hunger rating(before and 150 minutes after oral glucose challenge and start of glucagon/saline infusion)
- Glucose tolerance(0-120 minutes)
- Insulin sensitivity(0-120 minutes)
- Change in hormone levels(0-150 minutes)
- Brain response to food cues(before, 30 minutes and 120 minutes after oral glucose challenge and start of glucagon/saline infusion)