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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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Hellerup, Danemark, 2900
- Diabetes Research Division, Gentofte Hospital, Copenhagen
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Science basique
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur actif: T2DM, sevelamer
Patients with type 2 diabetes treated with sevelamer
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Comparateur placebo: T2DM, placebo
Patients with type 2 diabetes treated with placebo
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Comparateur actif: Healthy subjects, sevelamer
Healthy subjects treated with sevelamer
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Comparateur placebo: Healthy subjects, placebo
Healthy subjects treated with placebo
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Délai: -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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Délai: -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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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Blood analysis
Délai: 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
Délai: Fasting status on study days 1 and 7
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Inflammatory and metabolic markers
|
Fasting status on study days 1 and 7
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Faecal samples
Délai: 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
Délai: -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
Délai: 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
Délai: -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
Délai: -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
Délai: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
|
Appetite
|
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
|
Collaborateurs et enquêteurs
Collaborateurs
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- H-2-2013-148
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