Effect Dietary Fructose on Fructose Kinetics in Type 2 Diabetes

Effect Dietary Fructose on Fructose Kinetics in Type 2 Diabetes

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.

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.

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)