Effect Dietary Fructose on Fructose Kinetics in Type 2 Diabetes (ERIE)

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.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: high vs low fructose in caucasian dutch or surinamese asian type 2 diabetes subjects

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: cengiz callender, MD; Phone Number: 0031 20 5669111; Email: c.callender@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC location AMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: high fructose in caucasian dutch type 2 diabetes subjects; high (100gr/day) fructose diet for 4 weeks in type 2 diabetic subjects of Caucasian ethnicity.	Other: high vs low fructose in caucasian dutch or surinamese asian type 2 diabetes subjects; oral ingestion of food supplement for 4 weeks
PLACEBO_COMPARATOR: low fructose in caucasian dutch type 2 diabetes subjects; low fructose diet (<30 gram fructose intake per day isocaloric correction with dextrose) for 4 weeks in type 2 diabetic subjects of Caucasian ethnicity.	Other: high vs low fructose in caucasian dutch or surinamese asian type 2 diabetes subjects; oral ingestion of food supplement for 4 weeks
ACTIVE_COMPARATOR: high fructose in surinamese asian type 2 diabetes; high (100gr/day) fructose diet for 4 weeks in type 2 diabetic subjects of SAS ethnicity.	Other: high vs low fructose in caucasian dutch or surinamese asian type 2 diabetes subjects; oral ingestion of food supplement for 4 weeks
PLACEBO_COMPARATOR: low fructose in surinamese asian type 2 diabetes; low fructose diet (<30 gram fructose intake per day isocaloric correction with dextrose) for 4 weeks in type 2 diabetic subjects of SAS ethnicity.	Other: high vs low fructose in caucasian dutch or surinamese asian type 2 diabetes subjects; oral ingestion of food supplement for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fructose on glucose metabolism	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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in microbiota composition	correlate with changes in oral/fecal microbiota composition (diversity and strain)	4 weeks
changes in (postprandial )plasma metabolites	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	4 weeks

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: max nieuwdorp, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 5, 2023
• Primary Completion (ANTICIPATED): December 31, 2025
• Study Completion (ANTICIPATED): April 30, 2026

Study Registration Dates

• First Submitted: January 8, 2023
• First Submitted That Met QC Criteria: January 29, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 29, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2022.0606 - NL82353.018.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not allowed due to dutch GDPR regulations

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No