Type 2 Diabetes
Conditions
Brief summary
Determine the kinetics of fructose metabolism and its role as a metabolic substrate following a high (100gr/day) vs low fructose diet (\<30 gram fructose intake per day isocaloric correction with dextrose) in type 2 diabetic subjects of SAS or Caucasian ethnicity.
Detailed description
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 our gut 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 than Caucasians. Since gut microbiota is altered between these two ethnicities, we hypothesize that aberreant fructose catabolism in patients of SAS descent results in production of specific (gut microbiota derived) metabolites such as ethanol. In this study, fructose metabolism will thus be studied in patients of SAS and Caucasian Dutch descent. To this end the investigators will examine (13C 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 between these two ethnicities.
Interventions
OTHERhigh vs low fructose in caucasian dutch or surinamese asian type 2 diabetes subjects
oral ingestion of food supplement for 4 weeks
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
supplementation with either fructose or dextrose
Intervention model description
high versus low fructose diet for 4 weeks in either caucasian or surinamese asian type 2 diabetes patients
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 40 T2D patients (20 Caucasian and 20 SAS) * 40-70 years old * Male-female * BMI 25-35 kg/m2 * Stable anti diabetic drugs for 3 months (metformin is obligatory) * Stable medication use past 3 months * Able to give informed consent
Exclusion criteria
* \- Proton-pump inhibitor usage (known to effect gut microbiota) * GLP1, SGLT2i 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| fructose on glucose metabolism | 4 weeks | to correlate changes in oral fructose handling (measured by a fructose challenge test (AUC) with 13C6-labeled fructose in relation to metabolic effects on HOMA-IR and continuous glucose monitoring (Freestyle libre MAGE) at baseline and after 4 weeks of dietary intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in microbiota composition | 4 weeks | correlate with changes in oral/fecal microbiota composition (diversity and strain) |
| changes in (postprandial )plasma metabolites | 4 weeks | effects of the diet on body composition (measured via bio impedance analysis). We will also collects 24h feces and urine before each study visit to determine correlate with changes in (postprandial) untargeted plasma metabolites including endogenous ethanol |
Countries
Netherlands
Contacts
Primary Contactcengiz callender, MD
Backup Contactmax nieuwdorp, MD PhD
Outcome results
None listed