The Effect of Glucose-dependent Insulinotropic Polypeptide on the Alpha Cell Response to Hypoglycaemia in Patients with Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Total glucagon response
研究概览
简要总结
The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP[1-30] and GIP[1-42], in patients with type 1 diabetes. The main question it aims to answer is:
• What dose and isoform of GIP can most potently stimulate glucagon secretion during low blood sugar in patients with type 1 diabetes?
Participants will go through 5 experimental days that are identical except for an intravenous infusion of either placebo (saline), high or low dose GIP[1-42] or high or low dose GIP[1-30]. On all days, blood sugar will be lowered to around 2.5mmol/l for around 20-30min.
详细描述
After being informed about the study and the potential risks, each participant giving written informed consent will participate in five double-blinded experimental days (Day A-E) in a randomized order. Each experimental day is identical except for an intravenous infusion of either placebo (saline), high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-42] or high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-30].
Each experimental day will consist of an induction period where the participant's blood sugar is adjusted to around 5-6mmol/l with either insulin or glucose. Then the infusion of either placebo or hormone will be initiated and continued for 135 minutes.
After 30 minutes of hormone infusion, a separate infusion of insulin (1.5mU/kg/min) will be initiated and continued for 60 minutes. Based on frequent bed-side plasma glucose measurements and an adjustable 20% glucose infusion, plasma glucose will be clamped at 2.5 mmol/l until the insulin infusion is terminated. Following this is a 45 minute recovery period, during which a minimum of glucose is infused, to ensure a steady rise from 2.5mmol/l to 3.5mmol/l.
After the study day, patients will receive a meal to prevent subsequent hypoglycemia.
The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
The randomized order of infusions is blinded to both participant and investigator
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Caucasian men
- •Body mass index between 18-27kg/m2
- •Type 1 diabetes (T1D) (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/mol (<8.5%)
- •T1D duration of 2-30 years
- •C-peptide negative (stimulated C-peptide ≤ 100 pmol/l)
- •Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
- •Informed consent
排除标准
- •Anaemia (haemoglobin below normal range)
- •Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
- •Late microvascular complications except mild nonproliferative retinopathy
- •Allergy or intolerance to ingredients included in the standardized meals
- •Prior myocardial infarction or other cardiac events
- •Any physical or psychological condition that the investigator feels would interfere with trial participation
- •Treatment with any glucose-lowering drugs beside insulin
结局指标
主要结局
Total glucagon response
时间窗: 0-135minutes
Difference in baseline subtracted area under the curve (bsAUC) for glucagon between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
次要结局
- Total insulin response(0-135minutes)
- Difference in carboxy-terminal collagen crosslinks (CTX)(0-135minutes)
- Glucagon response during insulin infusion(30-90minutes)
- Difference in epinephrine(0-135minutes)
- Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)(0-135minutes)
- Total c-peptide response(0-135minutes)
- Difference in blood pressure(0-135minutes)
- Glucagon response after blood glucose (BG) falls below 3.0 mmol/L(t[BG<3.0] and the following 30 minutes)
- Glucagon response during recovery(90-135minutes)
- Difference in cortisol(0-135minutes)
- Difference in growth hormone hormones(0-135minutes)
- Amount of glucose infused(0-135minutes)
- Difference in norepinephrine(0-135minutes)
- Difference in heart rate(0-135minutes)
研究者
Asger Lund, MD
Principal investigator, MD, ph.d.
University Hospital, Gentofte, Copenhagen