The aim is to investigate changes in nocturnal and postprandial glucose and glycogen metabolism in individuals with IFG and IGT when compared to healthy, non-diabetic, overweight participants. In addition, it will be investigated if reducing…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Liver and muscle glycogen (13C-MRS)
- Whole body gluconeogenesis (fractional gluconeogenesis determined by
deuterated water x EGP determined by 6,6D2-glucose)
- Postprandial glucose uptake measured by [18F]-FDG-PET
Secondary outcome
Secundary:
- Whole body gluconeogenesis (fractional gluconeogenesis determined by
deuterated water x EGP determined by 6,6D2-glucose), upon Acipimox treatment
- Glucose tolerance determined by OGTT, upon Acipimox treatment
- Liver glycogen (13C-MRS), upon Acipimox treatment
Other:
- Hepatic acetylcarnitine determined by 1H-MRS as a measure for hepatic
gluconeogenesis
- Substrate oxidation (fat and carbohydrate oxidation overnight)
- Plasma metabolites related to energy metabolism
- Body composition (fat mass/fat free mass)
- Dynamic measurements of postprandial changes in water relaxation times
(1H-MRS)
Background summary
Type 2 diabetes mellitus (T2D) prevalence has increased drastically, making it
a major public health problem globally. The disease is preceded by a state of
prediabetes that is characterized by impaired fasting glucose (IFG) or impaired
glucose tolerance (IGT). While disturbances in glucose metabolism are
implicated in T2D pathogenesis, little is known about whether glucose
metabolism is differentially affected in IGT and IFG, especially during
postprandial and nocturnal states. This knowledge will help to develop more
targeted, individualized therapies that delay or even prevent the progression
of prediabetes into overt T2D.
Study objective
The aim is to investigate changes in nocturnal and postprandial glucose and
glycogen metabolism in individuals with IFG and IGT when compared to healthy,
non-diabetic, overweight participants. In addition, it will be investigated if
reducing gluconeogenesis in people with prediabetes can increase glucose
tolerance and fat oxidation by increased reliance on hepatic glycogen (through
a 4-day acipimox intervention).
Study design
This is an observational study in healthy overweight participants and
prediabetic participants with IFG or IGT, with an additional intervention of a
4- day Acipimox treatment in a subset of the prediabetic participant groups (10
IFG and 10 IGT). Volunteers will visit the university for a screening visit and
a visit with overnight stay for measurements of gluconeogenesis, glycogen,
glucose uptake, glucose tolerance and substrate oxidation. Ten participants
with IGT and 10 with IFG will follow a 4-day treatment with acipimox, followed
by a second overnight visit
(with measurements of gluconeogenesis, glycogen, glucose tolerance and
substrate oxidation).
Intervention
A subset of prediabetes individuals (first 10 IFG and 10 IGT subjects enrolled)
will receive a 4-day Acipimox treatment: 3x 250mg capsules for three days (one
with breakfast, one with lunch and one with evening snack) and 1x 250mg in the
morning of the last day.
Study burden and risks
Participants will not directly benefit from this study, but the obtained
results will provide insights in disturbances in nocturnal and postprandial
glucose and glycogen dynamics in prediabetes individuals which will help to
find new targets for the improvement of glucose tolerance and disturbed energy
metabolism in prediabetes. The burden predominantly consists of time
investment, the blood draws, and taking Acipimox medication for 4 days. In
addition, [18F]-FDG-PET and MRI measurements are performed, participants stay
in the respiration chamber overnight, and participants are asked to remain
fasted several times. In previous studies within our research group in which
[18F]-FDG-PET, MRI measurements, nights in the respiration chamber, blood
sampling and being fasted were a part of the study, the study was not
experienced as very burdening by participants. For the PET measurements,
participants will receive a bolus of [18F]-FDG of 4MBq/kg =0.072mSv/kg), which
is acceptable for research conducted in healthy adults. In this study,
participants are allowed to go out of the scanner, go to the toilet and drink
some water in between MRI scans, thereby limiting the burden of the MRI scans.
To limit the burden of the MRI protocol, participants are allowed to go out of
the scanner, go to the toilet and drink some water in between MRI scans. The
current study takes relatively little time. The risks, and its impact, of
participating in this study are limited.
Universiteitssingel 50
Maastricht 6229ER
NL
Universiteitssingel 50
Maastricht 6229ER
NL
Listed location countries
Age
Inclusion criteria
General for all groups:
-Participants are able to provide signed and dated written informed consent
prior to any study specific procedures
- Participants should have suitable veins for cannulation or repeated
venipuncture
- Women are post-menopausal (defined as at least 1 year post cessation of
menses)
- Aged >= 45 and <= 75 years
- Body mass index (BMI) 27 - 38 kg/m2
- Stable dietary habits (no weight loss or gain >5kg in the past 3 months)
- Sedentary lifestyle (not more than 2 hours of sports per week)
Prediabetic groups specifically:
IFG: fasting blood glucose between 6.1 and 6.9 mmol/L and 2-h plasma glucose
after ingestion of 75g oral glucose load below 7.8 mmol/L
IGT: fasting blood glucose below 6.1 mmol/L and 2-h plasma glucose after
ingestion of 75g oral glucose load between 7.8 and 11.1 mmol/L
Exclusion criteria
General for all groups:
- Previous enrolment in a clinical study with an investigational product during
the last 3 months or as judged by the Investigator
- Previously diagnosed with type 2 diabetes
- Patients with congestive heart failure and/or severe renal (eGFR <50mL/min)
and or liver insufficiency or another condition that may interfere with
outcomes measured in this study.
- Any contra-indication MRI scanning
- Alcohol consumption of >2 servings per day for men and >1 servings per day
for woman
- Smoking in the past 6 months
- Medication use that may influence main outcome parameters, specifically the
following types of medication: Type 2 diabetes medication, corticosteroids,
thyroid medication.
- Participation in research or medical examination that included PET scanning
in the last 3 months
Healthy overweight specifically:
- Any of the criteria mentioned above to define prediabetes
Prediabetic groups who will undergo acipimox treatment:
- Gout
- Hypersensitivity to acipimox or to any of the excipients in the tablet
- Peptic ulcer/dyspepsia
- Medication use that interfere with Acipimox (statins, fibrates).
A medical doctor will judge participation eligibility based on the medical
history questionnaire, medication use and fasting blood parameters. If the
medical doctor advises that a volunteer cannot participate, the volunteer will
be excluded from enrollment.
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 | NL84574.068.23 |