The primary objective of this study is to examine to what extent hepatic glycogen is decreased after a prolonged overnight fast in healthy volunteers with a normal weight and low liver fat percentage.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study outcome is the change in hepatic glycogen in response to a
9.5hrs and a 16 hrs fast, measured with 13C-magnetic resonance spectroscopy
(MRS).
Secondary outcome
Whole body fat oxidation measured using the respiratory quotient (VCO2/VO2)
during the night. Oxygen utilization and carbondioxide production are measured
using the respiration chamber.
Background summary
The body switches from glucose oxidation to fat oxidation when nutrient
availability is low, e.g. during a prolonged fast. This is associated with
depleting hepatic glycogen stores. In a previous study, where we investigated
hepatic glycogen depletion and substrate oxidation overnight in volunteers with
increased liver fat (NAFL), we found that hepatic glycogen did not decrease,
not even during a prolonged fast in this group of human participants.
Similarly, substrate oxidation did not show the typical increase in fat
oxidation during the night that is generally observed in healthy subjects. This
reflects that participants with NAFL do not easily reach a truly fasted state.
To link this finding to the metabolic phenotype of this subject group, we want
to investigate the same parameters in healthy lean volunteers and confirm that
in healthy subjects, metabolism does change during fasting. We hypothesize that
a prolonged overnight fast will lead to a depletion of hepatic glycogen stores
and stimulation of whole-body fat oxidation in healthy, lean adults, while this
was not the case in NAFL subjects.
Study objective
The primary objective of this study is to examine to what extent hepatic
glycogen is decreased after a prolonged overnight fast in healthy volunteers
with a normal weight and low liver fat percentage.
Study design
This is a randomized cross-over study comparing different overnight fasting
times (9.5 vs. 16h fasting) that will be conducted in 13 lean (BMI: 18.5 - 25)
males and postmenopausal females with a liver fat percentage <5%. The short and
long overnight fast conditions will be randomized, interspersed by a minimal
2-week wash-out period. In the study liver glycogen content(MRS), liverfat
oxidation (plasma beta-hydroxybutyrate), other plasma metabolites related to
energy metabolism and body composition(BodPod) will be measured in both
conditions.
Intervention
Short overnight fasting protocol
Subjects will receive a standardized snack at 16.30. At 23.00 subjects will
receive their standardized diner, where after subjects stay fasted for 9.5
hours.
Long overnightfasting protocol
Subjects will receive their standardized diner together with a snack at 16.30.
Hereafter, subjects stay fasted for16 hours.
Study burden and risks
The burden for the participant consists of time investment, fasting for a
prolonged period and blood draws. Participants are financially compensated for
their burden. Participation to this study only has minor risks for the
participants. Blood drawing could cause bruising and because participants with
contraindications for MRI scan are excluded for participation the risk of the
MRI scan is very low.
Universiteitssingel 50
Maastricht 6229ER
NL
Universiteitssingel 50
Maastricht 6229ER
NL
Listed location countries
Age
Inclusion criteria
- Participants are able to provide signed and dated written informed consent
prior to any study specific procedures
- Caucasian (people will be excluded when having a *50% racial African/Asian
background)
- Participants should have suitable veins for cannulation or repeated
venipuncture
- Women are post-menopausal (defined as at least 1 year post cessation of
menses)
- Men and women aged * 45 and * 75 years at the start of the study
- Body mass index (BMI) 18.5 * 25 kg/m2
- Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
- Sedentary lifestyle (not more than 3 hours of vigorous sports per week)
- Liver fat content <5%
Exclusion criteria
- Type 2 Diabetes Mellitus
- Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other)
- Any contraindication for MRI scanning
- Alcohol consumption of >2 servings per day
- Regular smoking
- No use of medication interfering with investigated study parameters (as
determined by responsible physician)
- Participants who do not want to be informed about unexpected medical
findings, or do not wish that their physician
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72118.068.20 |