Determine the kinetics of fructose metabolism and its role as a metabolic substrate following a high vs low fructose diet in subjects of SAS or Caucasian ethnicity.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints are changes in oral fructose handling (measured by a fructose
tolerance test with 120mg 13C6 -labeled fructose in relation to other
metabolic effects (eg on lipids, HOMA and continuous glucose monitoring
Freestyle libre) at baseline and after 4 weeks
Secondary outcome
Changes in gutmicrobiota composition between individuals of SAS or Caucasian
descent on high versus low fructose diet. Also, effects on body composition
(measured via bio impedance analysis) and 24h feces and urine for fructose
content and compliance will be studied. Finally, (postprandial) untargeted
plasma metabolites including endogenous ethanol at both timepoints will be done
to identify involved metabolic pathways.
Background summary
The prevalence and accompanying morbidity and mortality of obesity and type 2
diabetes (T2D) is increasing on a global scale. Unfortunately the underlying
(patho)physiological mechanisms are only partially understood. A key step in
the development of negative health effects of metabolic disease might be via
dietary fructose metabolism and its accompanying aberrant metabolite
production, in which ourgut microbiota plays a crucial role.
By bypassing the normal glucose metabolism pathway, fructose plays a role in
the development of metabolic disease such as diabetes en fatty liver disease.
The mechanism of this effect is unclear and possibly plays in the observation
of ethnic specific metabolic risk factors. That is, subjects of different
ethnicties (for instance South-Asian Surinamese (SAS)) have a higher risk and
worse trajectory of metabolic diseases then Caucasians. Since gutmicrobiota is
altered between these two ethnicities, we propose that aberreant fructose
catabolism in patients of South Asian Surinamese (SAS) results in production of
specific (gutmicrobiota derived) metabolites such as ethanol. In this study,
fructose metabolism will thus be studied in patients of South Asian Surinamese
(SAS) and Caucasian Dutch descent. To this end we will examine (stable isotope
based) fructose fluxes before and after randomizing subjects into a four-week
high- or low fructose diet, this study aims to elucidate the physiological and
microbial catabolism of fructose and possible differences in these two
ethnicities.
Study objective
Determine the kinetics of fructose metabolism and its role as a metabolic
substrate following a high vs low fructose diet in subjects of SAS or Caucasian
ethnicity.
Study design
Isocaloric non-blinded single centre dietary intervention study
Intervention
High (100gr/day) vs Low (30gr/day) fructose diet for 4 weeks. Fructose will be
ingested via regular dietary route (food/drink changes) and the process will be
monitored by a dietician.
Study burden and risks
The total duration of the study is four weeks and participants will visit the
AmsterdamUMC, location AMC four times. All participants are required to fill
out food diaries three days per week and have weekly contact with the
dietician. Subjects are required to collect 24h urine and feces at baseline,
week 2 and week 4 of the study. Furthermore, subjects will undergo multiple
blood sampling after a Fructose Challenge Test (FCT). The proposed diet is safe
and no immediate harm is likely to occur. However, glycaemic control of T2D can
theoretically worsen. Therefore, we measure HbA1c, fasting glucose and perform
continuous glucose monitoring throughout the study. Subjects will be
discontinued from the study if HbA1c >9% (75mmol/mol). In total subjects will
spend 13 hours in Amsterdam UMC, location AMSTERDAM UMC, location AMC :2x 6.25
h for the FCT plus REE/BIA at baseline and 4 weeks, as well as 25 minutes
during screening and 25 minutes during test day 2. We will collect 170ml blood
(at baseline, week 2 and week 4) in total. Subjects will not undergo invasive
procedures, besides venous blood draw through a peripherally placed cannula
(therefore only 1 puncture is needed per test day).
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- 40 T2D patients (20 Caucasian and 20 SAS)
- 40-70 years
- BMI 25-35
- Stable anti diabetic drugs for 3 months (metformin is obligatory)
- Stable medication uses past 3 months
- Able to give informed consent
Exclusion criteria
- Proton-pump inhibitor usage (known to effect gut microbiota)
- GLP1 or insulin use (known to effect gut microbiota)
- Antibiotic for the past 3 months (known to effect gut microbiota)
- Probiotic or symbiotic usage (known to effect gut microbiota)
- Pregnant women
- Chronic illness (including a known history of heart failure, renal failure
(eGFR <30 ml/min), pulmonary disease, gastrointestinal disorders, or
hematologic diseases), or other inflammatory diseases
- Active infection
- Previous intestinal (e.g., bowel resection/reconstruction) surgery
- Smoking (due to its influence on gut microbiome)
- Vegetarian diet (since they have different microbiota)
- >6 alcohol units per day or >14 alcohol units per week
- Active malignancy
- HbA1c >9% (75mmol/mol)
- The subject is already involved in a clinical trial
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 | NL82353.018.22 |