To assess whether changes in insulin sensitivity through dietary interventions affect postprandial bile acid metabolism and kinetics. Secondary objective: to assess TGR5 and FXR mediated pathways in insulin resistant and insulin sensitive states.
ID
Source
Brief title
Condition
- Malabsorption conditions
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in postprandial bile acid levels in plasma, bile acid pool
composition and bile acid kinetic parameters
Secondary outcome
Changes in postprandial glucose kinetics and glucoregulatory hormones,
activation of TGR5 and FXR mediated pathways in muscle and fat
Resting energy expenditure
Gastric emptying
Adherence to diet
Microbiome composition
Background summary
Traditionally, bile acids (BAs) have been thought to serve the purpose of
emulsifying nutrients. However, evidence has emerged from animal and in-vitro
studies that BAs also play a role in the regulation of energy metabolism,
particularly glucose and fat metabolism. This is mediated through the BA
receptors TGR5 and FXR. Modulation of BA pool composition affects insulin
sensitivity in mice, suggesting a possible therapeutic pathway for type 2
diabetes mellitus. Conversely, BA metabolism is altered in type 2 diabetes in
humans. This raises the question whether altered BA metabolism is a determinant
or a consequence of insulin sensitivity. It is unknown whether postprandial
bile acid levels are related to insulin sensitivity.
Study objective
To assess whether changes in insulin sensitivity through dietary interventions
affect postprandial bile acid metabolism and kinetics. Secondary objective: to
assess TGR5 and FXR mediated pathways in insulin resistant and insulin
sensitive states.
Study design
Observational study
Study burden and risks
Subjects will undergo 2 invasive procedures (2 mixed-meal tests) with IV
cannulation and frequent blood sampling. Total blood volume sampled will be 248
ml. During the mixed-meal test fat and muscle biopsies will be obtained (4
timepoints study total) and resting energy expenditure will be determined (6x
study total) via indirect calorimetry. This requires the subject to lie flat on
his back and to breathe into a mask for 20 minutes.
Subjects will spend approximately 17,5 hours to study days, including inclusion
and screening.
In addition, subjects will undergo a diet intervention for two weeks. This is
either a low-calorie diet (450 kcal/day), or a high-fat-low-carbohydrate diet.
Both diets are a moderate burden on subjects.
The total burden of this study is high by our estimate, mainly because of the
repeated invasive measurements and the burden of strictly adhering to a diet.
Important risks are: infection, haematoma and phlebitis for the invasive
procedures. These risks are low.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers
or
Insulin resistant (HOMA-IR > 2.7)
Exclusion criteria
*Use of medication that interferes with insulin metabolism (such as sulfonylureas, meglitinides, metformin, thiazolidenidiones, acarbose, dipeptidyl peptidase-4-inhibitors) or insulin.
*Use of medication that interferes with BA metabolism (colesevelam, colestimide, ursodeoxycholic acid).
Previous cholecystectomy
Weight increase or decrease >10% in previous 3 months
Alcohol use >2 units/day
Pregnancy and use of oral contraceptives in females
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL41901.018.12 |
| OMON | NL-OMON25160 |