Effect of Bile Acid Sequestration on Postprandial GLP-1 Secretion, Glucose Homeostasis and Gut Microbiota
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
研究概览
简要总结
Accumulating evidence suggests that bile acids and bacteria in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. At the same time, bile acids and gut bacteria are interdependent. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion or gut bacteria composition and consequently affect glucose homeostasis.
The current study is a human interventional study with 7-day ingestion of a bile acid sequestrant or placebo, preceded and followed by meal tests and faecal sampling. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion, gut microbiota and glucose homeostasis in patients with type 2 diabetes and healthy individuals. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer was recently shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes.
The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in the postprandial gut hormone secretion and gut bacteria composition. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion, gut bacteria and glucose metabolism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Both groups
- •Caucasian ethnicity
- •Normal haemoglobin
- •Age above 35 years and below 80 years
- •Informed and written consent
- •BMI > 23 kg/m2 and <35 kg/m2
- •Patients with type 2 diabetes
- •Type 2 diabetes for at least 3 months
- •Diagnosed according to the criteria of the World Health Organization (WHO)
- •Healthy Subjects
- •Normal fasting plasma glucose (FPG) <6.5 mM and
- •Normal glycated haemoglobin (HbA1c) <6.0 %
排除标准
- •Both groups
- •Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
- •Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
- •Hypo- or hyperphosphataemia
- •Nephropathy (serum creatinine >150 µM and/or albuminuria
- •Treatment with medicine that cannot be paused for 12 hours
- •Intake of antibiotics six months prior to study
- •Hypo- or hypercalcaemia
- •Hypo- and hyperthyroidism
- •Treatment with oral anticoagulants
- •Active or recent malignant disease
- •Any treatment or condition requiring acute or sub-acute medical or surgical intervention
- •Lack of effective birth control in premenopausal women
- •Positive pregnancy test on study days in premenopausal women
- •Tobacco smoking
- •Any condition considered incompatible with participation by the investigators
- •Patients with type 2 diabetes
- •Treatment with insulin
- •Treatment with incretin-based therapy
- •Healthy Subjects
- •Diabetes or
- •prediabetes (fasting plasma glucose levels >6.5 mM or HbA1c >6.0%)
- •First-degree relatives with diabetes
研究组 & 干预措施
T2DM, sevelamer
Patients with type 2 diabetes treated with sevelamer
干预措施: Sevelamer 1600 mg TID for 7 days (Drug)
T2DM, placebo
Patients with type 2 diabetes treated with placebo
干预措施: Placebo 1600 mg TID for 7 days (Drug)
Healthy subjects, sevelamer
Healthy subjects treated with sevelamer
干预措施: Sevelamer 1600 mg TID for 7 days (Drug)
Healthy subjects, placebo
Healthy subjects treated with placebo
干预措施: Placebo 1600 mg TID for 7 days (Drug)
结局指标
主要结局
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
时间窗: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1 and 7 (meal tests start at 0 min)
Postprandial responses of glucagon-like peptide-1 (GLP-1)
次要结局
- Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)(-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1 and 7 (meal tests start at 0 min))
研究者
Andreas Brønden
MD
University Hospital, Gentofte, Copenhagen