Digital Twin - Modelling Postprandial Triglyceride and Glucose Responses

Giving personalised dietary advice will help mitigate the postprandial increases in TG and glucose levels, and will assist in the battle against the increase in nutrition-related diseases, such as cardiovascular diseases. Being able to predict postprandial responses, will be a first step to personalised dietary advice.

The primary objective of this study is to validate the prediction model on the effect of a standardized mixed meal challenge on postprandial TG levels in a heterogenous group of middle-aged, overweight to obese individuals. The secondary objectives are 1) to improve the accuracy of the predicted postprandial TG responses by increasing the number of postprandial TG measurements, 2) to determine which parameters can improve the accuracy of the predicted postprandial TG responses, 3) to determine if we can predict the effect of a standardized mixed meal challenge on postprandial glucose levels in a heterogenous group of middle-aged, overweight to obese individuals, and 4) to determine which parameters can improve the accuracy of the predicted postprandial glucose responses. Another objective is to validate dried blood spots postprandial triglyceride concentrations against venous blood concentrations.

There are minor risks for the research subjects of this study. Research subjects will invest approximately 13.5 hours in the study. They will visit the Wageningen University research facility three times and Hospital Gelderse Vallei once.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism; Lipid Metabolism
• Intervention / Treatment: Diagnostic test: Mixed meal challenge test; Diagnostic test: MRI; Diagnostic test: DEXA; Device: Freestyle Libre; Device: ActivPAL3

Detailed Description

Elevated triglyceride (TG) and glucose levels are major risk factors for cardiovascular diseases. Therefore, mitigating the postprandial increase in TG and glucose levels may help curb a person's risk of developing cardiovascular diseases. Current strategies to stimulate people to adopt a healthy lifestyle, however, are still insufficient. This is partly due to the fact that nutritional advice is nowadays still given at the population level via general nutrition guidelines, while nutritionist have long been aware that what works for one person may not work for another. Giving personalised dietary advice will help mitigate the postprandial increases in TG and glucose levels, and will assist in the battle against the increase in nutrition-related diseases, such as cardiovascular diseases. Being able to predict postprandial responses, will be a first step to personalised dietary advice.

The primary objective of this study is to validate the prediction model on the effect of a standardized mixed meal challenge on postprandial TG levels in a heterogenous group of middle-aged, overweight to obese individuals. The secondary objectives are 1) to improve the accuracy of the predicted postprandial TG responses by increasing the number of postprandial TG measurements, 2) to determine which parameters can improve the accuracy of the predicted postprandial TG responses, 3) to determine if we can predict the effect of a standardized mixed meal challenge on postprandial glucose levels in a heterogenous group of middle-aged, overweight to obese individuals, and 4) to determine which parameters can improve the accuracy of the predicted postprandial glucose responses. Another objective is to validate dried blood spots postprandial triglyceride concentrations against venous blood concentrations.

Digital twin is an observational study with three visits, including one mixed meal challenge test day.

Study population consists of 38 volunteers, 45-75 year old, BMI between 25-35 kg/m2.

The primary study parameter is the postprandial triglyceride responses in blood upon a mixed meal challenge. The secondary study parameters are: postprandial responses in the blood upon a mixed meal challenge, and extensive phenotyping of the subjects by collecting data on fasting blood profiles of micronutrients, metabolites, and proteins, continuous blood glucose levels (Freestyle Libre), body fat composition (DEXA), liver fat percentage (MRI), habitual dietary intake (FFQ), and physical activity (ActivPAL3).

This study is related to a broad general population. There are minor risks for the research subjects of this study. Consumption of the liquid mixed meal may cause some gastro-intestinal discomfort. Blood sampling will be performed via a cannula and the insertion can be a bit painful and may cause a bruise. The amount of blood that is drawn from subjects is within acceptable limits (total amount collected = 186mL). The radiation dose received during the DEXA scan for measuring body composition, is negligible compared to the average dose each person in the Netherlands receives per year. Research subjects will invest approximately 13.5 hours in the study. They will visit the Wageningen University research facility three times: once for a short screening, once to collect phenotyping data, and once for a mixed-meal challenge test day. In addition, they will visit Hospital Gelderse Vallei once for an MRI measurement.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6708 WG
      • Stichting Wageningen Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The population of the study will consist of generally healthy males and females aged 45-75, with a BMI ranging from 25 to 35 kg/m2. For this study, we will include 38 research subjects (aiming at 50% females).

Description

Inclusion Criteria:

• Male or female
• Age 45-75 y
• BMI 25-35 kg/m2
• Suitable veins for insertion of cannula

Exclusion Criteria:

• Having a gastro-intestinal disease, such as celiac disease, Crohn's disease, or Ulcerative colitis
• Having a history of intestinal surgery that might interfere with study outcomes, as determined by the medical supervisor. This does not include an appendectomy or cholecystectomy
• Presence of significant systemic diseases, such as diabetes mellitus, cancer, cardiovascular disease or respiratory disease, as determined by the medical supervisor
• Use of medications known to interfere with glucose or lipid homeostasis (e.g. corticosteroids, cholesterol-lowering medication, insulin, metformin), as determined by medical supervisor
• Blood clotting disorders
• Unstable body weight (weight gain or loss >3 kg in the past three months)
• Reported slimming, medically prescribed or other extreme diets
• Alcohol consumption >21 glasses a week
• Anaemia (Hb values <7.5 mmol/L for women and <8.5 mmol/L for men; checked at screening)
• Pregnant, lactating or wishing to become pregnant in the period of the study (self-reported)
• Having a pacemaker, implantable cardioverter-defibrillator, hearing implant, internal insulin pump, neurostimulator, aneurysm clips placed before 1990, or metal splinter in the eye
• Having claustrophobia
• Not willing to give up blood donation during the study
• Food allergies or intolerances for products that we use in the study
• Unwilling to consume non-vegan test meal
• Recent use of antibiotics (<3 months prior to study start)
• Current smokers
• Abuse of soft and/or hard drugs
• Participation in another clinical trial at the same time
• Being an employee of the Food, Health & Consumer Research group of Wageningen Food & Biobased Research or Human Nutrition and Health Department of Wageningen University

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	Baseline
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	15 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	30 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	45 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	60 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	90 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	120 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	150 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	180 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	210 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	240 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	270 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	300 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	330 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	360 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	390 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	420 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	450 minutes post-ingestion
Postprandial triglycerides blood levels	Postprandial triglyceride responses in blood upon a mixed meal challenge	480 minutes post-ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	Baseline
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	30 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	60 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	90 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	120 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	180 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	240 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	Baseline
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	30 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	60 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	90 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	120 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	180 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	240 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	15 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	45 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	150 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	210 minutes post-ingestion
Postprandial glucose blood levels	Postprandial glucose responses in blood upon a mixed meal challenge	480 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	15 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	150 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	210 minutes post-ingestion
Postprandial insulin blood levels	Postprandial insulin responses in blood upon a mixed meal challenge	480 minutes post-ingestion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose profile	Continuous blood glucose levels	Continuous for 5 days
Physical activity	Continuous physical activity levels	Continuous for 5 days
Anthropometrics	Waist-to-hip ratio	Baseline
Body composition	Body composition measurement with Dexa scan	Baseline
Habitual dietary intake	Habitual dietary intake assessment with FFQ	Baseline
Liver fat	Liver fat percentage assessment with MRI	Baseline
Micronutrient levels in blood	Micronutrient levels	Baseline
Metabolite levels in blood (full profile)	Metabolomics	Baseline
Protein levels in blood (full profile)	Proteomics	Baseline
Triglyceride blood levels	Triglyceride measurement in dried blood spots in fingerprick blood upon a mixed meal challenge	Baseline
Triglyceride blood levels	Triglyceride measurement in dried blood spots in fingerprick blood upon a mixed meal challenge	120 minutes post-ingestion
Triglyceride blood levels	Triglyceride measurement in dried blood spots in fingerprick blood upon a mixed meal challenge	240 minutes post-ingestion
Triglyceride blood levels	Triglyceride measurement in dried blood spots in fingerprick blood upon a mixed meal challenge	480 minutes post-ingestion

Collaborators and Investigators

• Sponsor: Wageningen University and Research
• Investigators: Principal Investigator: Diederik J Esser, PhD, Wageningen University & Research

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Actual): June 14, 2022
• Study Completion (Actual): June 29, 2022

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: postprandial; lipids; glucose; dried blood spot; prediction model; metabolic responses
• Other Study ID Numbers: NL79685.091.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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