Effect of Bile Acid Sequestration on Postprandial GLP-1 Secretion, Glucose Homeostasis and Gut Microbiota
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.
研究概览
研究类型
注册 (实际的)
阶段
- 不适用
联系人和位置
学习地点
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Hellerup、丹麦、2900
- Diabetes Research Division, Gentofte Hospital, Copenhagen
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
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 %
Exclusion Criteria:
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器：T2DM, sevelamer
Patients with type 2 diabetes treated with sevelamer
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安慰剂比较：T2DM, placebo
Patients with type 2 diabetes treated with placebo
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有源比较器：Healthy subjects, sevelamer
Healthy subjects treated with sevelamer
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安慰剂比较：Healthy subjects, placebo
Healthy subjects treated with placebo
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
大体时间：-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)
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Postprandial responses of glucagon-like peptide-1 (GLP-1)
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-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)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
大体时间：-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)
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Postprandial responses of various other gut hormones
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-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)
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Blood analysis
大体时间：Fasting status on study days 1 and 7
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Lipids
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Fasting status on study days 1 and 7
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Blood analysis
大体时间：Fasting status on study days 1 and 7
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Inflammatory and metabolic markers
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Fasting status on study days 1 and 7
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Faecal samples
大体时间：Prior to study days 1 and 7
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Gut microbiota composition
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Prior to study days 1 and 7
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Blood analysis of paracetamol
大体时间：-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Assessment of gastric emptying
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-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Bodyweight
大体时间：Fasting state on study days 1 and 7
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Fasting state on study days 1 and 7
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Indirect calorimetry
大体时间：-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Basal metabolic rate
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-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Ultrasound measurements
大体时间：-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Gall bladder volume
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-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Visual analog scale score
大体时间：-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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Appetite
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-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
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合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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