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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
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Hellerup, Dinamarca, 2900
- Diabetes Research Division, Gentofte Hospital, Copenhagen
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador Ativo: T2DM, sevelamer
Patients with type 2 diabetes treated with sevelamer
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Comparador de Placebo: T2DM, placebo
Patients with type 2 diabetes treated with placebo
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Comparador Ativo: Healthy subjects, sevelamer
Healthy subjects treated with sevelamer
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Comparador de Placebo: Healthy subjects, placebo
Healthy subjects treated with placebo
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Prazo: -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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Prazo: -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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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
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Blood analysis
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: -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
Prazo: 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
Prazo: -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
Prazo: -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
Prazo: -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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Colaboradores e Investigadores
Patrocinador
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- H-2-2013-148
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