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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Hellerup, Dinamarca, 2900
- Diabetes Research Division, Gentofte Hospital, Copenhagen
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: T2DM, sevelamer
Patients with type 2 diabetes treated with sevelamer
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Comparador de placebos: T2DM, placebo
Patients with type 2 diabetes treated with placebo
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|
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Comparador activo: Healthy subjects, sevelamer
Healthy subjects treated with sevelamer
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Comparador de placebos: Healthy subjects, placebo
Healthy subjects treated with placebo
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Periodo de tiempo: -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)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Periodo de tiempo: -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 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)
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Blood analysis
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: -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
Periodo de tiempo: Fasting state on study days 1 and 7
|
Fasting state on study days 1 and 7
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|
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Indirect calorimetry
Periodo de tiempo: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
|
Basal metabolic rate
|
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
|
|
Ultrasound measurements
Periodo de tiempo: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
|
Gall bladder volume
|
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
|
|
Visual analog scale score
Periodo de tiempo: -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
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- H-2-2013-148
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