The aim of the present study is to examine the interaction (and underlying mechanisms) between hepatic fructose and glucose metabolism in humans. The first objective is to determine the dose-effect relationship between oral fructose and the plasma…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The area under the curve (AUC) for plasma glucose and lactate excursions during
an OGTT will be calculated.
The glucose and lactate AUC*s for the OGTT without fructose will be compared to
the glucose and lactate AUC*s for the OGTT(s) with fructose.
Secondary outcome
Secondary parameters:
Serum fructose, insulin, triglycerides, urate and beta-hydroxybutyrate levels
will be measured at baseline and the end of each OGTT and compared with the
OGTT without fructose.
Urinary fructose will be measured at the end of each OGTT and compared with the
OGTT without fructose.
Furthermore, plasma will be stored future analyses.
Other study parameters include:
• Age
• Sex
• BMI
• Waist and hip circumference
• Fasting plasma glucose
• Fasting serum insulin
• Fasting serum lipids (total cholesterol, HDL cholesterol, LDL cholesterol,
triglycerides)
• Systolic and diastolic blood pressure
Background summary
Despite the consensus that added sugars - i.e. all sugars that are added during
food manufacturing and preparation - play an important role in the current
epidemic of obesity and consequently type 2 diabetes mellitus (T2DM),
dyslipidaemia and cardiovascular disease (CVD), there is an ongoing discussion
whether the type of sugar, i.e. fructose or glucose, matters. Previous animal
studies have suggested that hepatic fructose and glucose metabolism are linked
through the action of glucokinase regulatory protein (GKRP).
Study objective
The aim of the present study is to examine the interaction (and underlying
mechanisms) between hepatic fructose and glucose metabolism in humans. The
first objective is to determine the dose-effect relationship between oral
fructose and the plasma glucose and lactate excursions during an oral glucose
tolerance test (OGTT).
The second objective is to elucidate the role of GKRP in the fructose-induced
change in plasma glucose and lactate excursions during an OGTT.
Study design
This study consists of:
Substudy I) A single-blind, dose response study in healthy individuals
(objective 1);
Substudy II) A single-blind, cross-over intervention study in carriers of
aldolase B mutation, carriers of glucokinase mutation and healthy controls
(objective 2).
Intervention
For substudy I, all participants will undergo eight OGTTs in total, including
one standard OGTT, five standard OGTTs with addition of different dosages of
fructose, one standard OGTT with addition of glucose (iscaloric control), and
oral test with fructose only (*isofructose* control), after an overnight
fasting in a random sequence (with at least 4 days interval between each OGTT)
on different occasions.
For substudy I protocol amendment, the 10 additional participants will undergo
four OGTTs in total, including one standard OGTT and three standard OGTTs with
addition of different dosages of fructose, after an overnight fasting in a
random sequence on different occasions.
For substudy II, all participants will undergo one standard OGTT without
fructose and one standard OGTT with fructose, after an overnight fasting in a
random sequence on different occasions.
Study burden and risks
For substudy I, all participants will undergo eight OGTTs in total.
For substudy I protocol amendment, the 10 additional participants will undergo
four OGTTs in total.
For substudy II, all participants will undergo two OGTTs in total.
In total, 85 ml blood will be collected per OGTT (Substudy I: ~680 ml total
blood; Substudy I protocol amendement: ~340 ml total blood; Substudy II: ~170
ml total blood).
Administration of an oral glucose load may cause faintness, nausea and
vomiting.
Venous blood withdrawal using the cannula technique can occasionally cause a
local haematoma.
All participants will undergo a general health check regarding cardiovascular
risk factors which may be of potential benefit.
Universiteitssingel 50
Maastricht 6229ER
NL
Universiteitssingel 50
Maastricht 6229ER
NL
Listed location countries
Age
Inclusion criteria
Substudy I:
Healthy men, age 18-75 years, blood Hb >= 8,2 mmol/L.
Healthy women, age 18-75 years, blood Hb >= 7,3 mmol/L, either postmenopausal
women or premenopausal using an oral contraceptive without a *stop week*,
Substudy I protocol amendment for the 10 additional study participants:
Healthy men, age 18-75 years.
Healthy women, age 18-75 years, either postmenopausal women or premenopausal
using an oral contraceptive without a *stop week*,
Substudy II:
a) Genetic diagnosis (i.e. heterozygous carrier) of aldolase B mutation, age
18-75 years.
b) Genetic diagnosis of Maturity-Onset Diabetes of the Young Type 2 (MODY-2),
i.e. carrier of glucokinase mutation, age 18-75 years.
c) Healthy individuals, age 18-75 years.
Exclusion criteria
• Fasting blood glucose >11 mmol/L;
• Clinical diagnosis of diabetes including type 1 and type 2;
• Use of medications known to interfere with glucose homeostasis (i.e.
corticosteroids);
• Medical conditions that can interfere with the study outcome (i.e.
gastrointestinal disease);
• Cancer, end-stage liver, kidney, cardiac or lung disease;
• Unstable weight for 3 months prior to inclusion (i.e. 5% change in bodyweight
(13));
• Abuse of drugs and/or alcohol;
• Pregnancy;
• Physical stress one month prior to inclusion (i.e. post-surgery, trauma or
infection or extreme psychological stress);
• Periodic hypokalemic paralysis;
• Inability to give inform consent.
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 | NL68189.068.18 |