Examining the Effect of Endogenous Glucagon-like Peptide-1 on Glucagon Secretion in Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- bsAUC Glucagon
研究概览
简要总结
Type 1 diabetes is a serious and burdensome disease that carries the risk of severe complications and premature death, partly due to low blood sugar, also called hypoglycaemia. This is a constant threat, as individuals with type 1 diabetes lack the body's natural safeguard against low blood sugar: the hormone glucagon, which is normally released from the pancreas.
Recent research in mice suggests that this missing safeguard may be due to an imbalance in the hormones released from different cells in the pancreas. More specifically, glucagon-like peptide-1 (GLP-1) appears to play a role in the lack of glucagon secretion. By blocking this hormone using the substance exendin(9-39)NH₂, normalization of glucagon release during low blood sugar has been observed in mice with type 1 diabetes.
The present study aims to investigate whether the same mechanism applies in humans with type 1 diabetes. If confirmed, this finding could form the basis for a novel adjunct treatment to insulin therapy and thereby potentially reduce the risk of hypoglycaemia in this patient group.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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 ethnicity
- •Age between 18 and 70 years
- •T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mmol/mol (<8.5%)
- •Body mass index between 19 and 30 kg/m2
- •T1D duration of 2-30 years
- •C-peptide negative (5 gram arginine-stimulated C-peptide ≤100 pmol/l)
- •Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
排除标准
- •Anaemia (haemoglobin below normal range)
- •Late microvascular complications except mild non-proliferative retinopathy
- •Liver disease (Evaluated by alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or a history of hepatobiliary disorder
- •Kidney disease (serum creatinine above normal range)
- •Treatment with any glucose-lowering drugs beside insulin
- •Active or recent (within 5 years) malignant disease
- •Regular tobacco smoking or use of other nicotine-containing products
- •Any condition considered incompatible with participation by the investigators.
研究组 & 干预措施
Exendin(9-39)NH2
GLP-1 antagonist
干预措施: exendin(9-39)amide (Drug)
Placebo
Saline
干预措施: Saline (0.9% NaCl) (Drug)
结局指标
主要结局
bsAUC Glucagon
时间窗: 0-135 minutes
Entire study periode
次要结局
- bsAUC of Glucagon(30-90 minutes)
- Total Glucose infused(90-135 minutes)
- Glucose infused (entire period)(0-135 minutes)
- GLP-1(0-135 minutes)
- Cortisol(0-135 minutes)
研究者
Asger Lund, MD
Associate professor, MD, Ph.D.
University Hospital, Gentofte, Copenhagen