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The RepEAT Study: Individual Differences in Postprandial Glucose Responses and the Relation With Diet and Phenotype

Not Applicable
Completed
Conditions
Postprandial Glucose Responses
Glucose Metabolism
Registration Number
NCT05456815
Lead Sponsor
Wageningen University
Brief Summary

Postprandial glucose responses are related to an increased risk of developing cardiometabolic diseases. Existing research recognizes the presence of inter-individual variation in postprandial glucose responses to the same meal or food product. However, the role of diet and phenotype in postprandial glucose responses is unclear.

The primary objective of this study is to determine the variation in postprandial glucose responses to the same meals/food products and how this relates to the variation in postprandial glucose responses over a 9-week fully controlled dietary intervention within and between individuals. Our secondary objectives are to investigate the difference between postprandial glucose responses to original products and postprandial glucose responses to reformulated products, and to examine the relation between postprandial glucose responses and short-term well-being. In addition, we aim to study the relation between variation in postprandial glucose and phenotype, including immune function, cognitive performance, and microbiota composition.

63 apparently healthy men and women with a BMI of 25-40 kg/m2, aged 45-75 years will be included in the study, comprising a characterization period of 3 weeks and a completely controlled dietary intervention of 9 weeks. During these 9 weeks, glucose will be continuously monitored to measure postprandial glucose responses to standard foods/meals.

There are minor risks for the research subjects of this study. Research subjects will invest approximately 85 hours in the study. During the characterization week, subjects will visit the Wageningen University 3 times and Hospital Gelderse Vallei (Ede, The Netherlands) once. During the controlled dietary intervention, subjects will visit the Wageningen University 2-3 times a week.

Detailed Description

Postprandial glucose responses are related to an increased risk of developing cardiometabolic diseases. Existing research recognizes the presence of inter-individual variation in postprandial glucose responses to the same meal or food product. However, the role of diet, i.e. the other consumed food products and meals, and phenotype in postprandial glucose responses is unclear. A repetitive design and a standardized diet are necessary to determine the variation in postprandial glucose responses to a meal or food product irrespective of the diet.

The primary objective of this study is to determine the variation in postprandial glucose responses to the same meals/food products and how this relates to the variation in postprandial glucose responses over a 9-week fully controlled dietary intervention within and between individuals. Our secondary objectives are to investigate the difference between postprandial glucose responses to original products and postprandial glucose responses to reformulated products, and to examine the relation between postprandial glucose responses and short-term well-being. In addition, we aim to study the relation between variation in postprandial glucose and phenotype, including immune function, cognitive performance, and microbiota composition.

The study population consists of 63 apparently healthy men and women with a BMI of 25-40 kg/m2, aged 45-75 years, and who are weight stable (± \<3 kg) for at least three months prior to inclusion.

The study comprises a characterization period of three weeks, followed by a fully controlled dietary intervention trial of nine weeks. In the characterization period, the phenotype of participants will be determined by measures on anthropometrics, immune function, oxidative stress, advanced glycation end-products, cognitive performance, microbiota and gut health, amylase, genetics, and circulating metabolites. The dietary intervention consists of three repetitive rounds of three weeks, in which we test food products in a cross-over setting. Participants will consume test products that fall in the same food category, but differ in glycaemic index/carbohydrate content. Part of these products is provided by industrial partners, of which the original products are reformulated to be reduced in glycaemic index/carbohydrate content. During the 9-week dietary intervention all foods are provided, giving us a complete and detailed picture of food and nutrient intake during this period. The standardized diet follows the average consumption pattern of the study population. Throughout the intervention, interstitial glucose concentrations will be measured using continuous glucose monitoring (CGM) and physical activity will be monitored with an accelerometer.

This study is related to a broad general population. There are minor risks for the research subjects of this study. Placing a continuous glucose sensor generally does not cause pain, but could result in the loss of a drop of blood, or slight skin irritation after wearing. Blood sampling will be performed via a cannula or venapunction and the insertion can be a bit painful and may cause a bruise. During the characterization period, in total 215 mL of blood will be collected in a 3-week timespan. In the following 9 weeks 108 mL, and at the end of the intervention 34 mL blood will be collected. Research subjects will invest approximately 85 hours in the study. During the characterization week, subjects will visit the Wageningen University 3 times and Hospital Gelderse Vallei (Ede, The Netherlands) once. During the controlled dietary intervention, subjects will visit the Wageningen University 2-3 times a week.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
63
Inclusion Criteria
  • Apparently healthy men and women
  • BMI of 25 - 40 kg/m2
  • Age 45-75 years
  • Weight stable (± <3 kg) for at least two months prior to inclusion
Exclusion Criteria
  • Diagnosed with type 1 or type 2 diabetes
  • Diseases or prior surgeries affecting the stomach, liver, or intestines
  • Food allergies/intolerances for products used in the study design
  • Receiving medication or supplements interfering with glucose metabolism (as judged by our research physician)
  • Regular use of medication interfering with immune function (e.g. corticosteroids, immune blockers, as judged by our research physician)
  • Donated blood within 2 months prior to the screening
  • Anaemia defined as Hb concentrations <8.5 mmol/L for men and <7.5 mmol/L for women
  • Veins not suitable for venflon needle
  • Allergy/intolerance to medical skin adhesives
  • Dietary habits interfering with the study design (e.g. vegetarian, vegan, ketogenic diet)
  • Intention to change the intensity of exercise during the study period
  • Current smokers
  • Alcohol intake ≥14 alcoholic beverages per week (women) or ≥21 alcoholic beverages per week (men)
  • Being pregnant or lactating
  • Use of soft and/or hard drugs
  • Unable/unwilling to download a research application on the mobile phone
  • Participation in another study that involves an intervention within two months prior to the intervention
  • Working at the division of Human Nutrition and Health of Wageningen University and Research or the Food, Health and Consumer research group of Wageningen University and Biobased Research

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Blood glucose profileContinuous for 9 weeks

Interstitial glucose concentrations, as measured by continuous glucose monitoring

Secondary Outcome Measures
NameTimeMethod
Plasma insulin response fries C2 hours post-ingestion

Plasma insulin response to fries type C

PBMC cytokine productionEnd of intervention (week 12)

PBMC cytokine production as measured by intracellular staining

Fasting glucose concentrationBaseline

Fasting glucose concentration

Plasma insulin response yoghurt B2 hours post-ingestion

Plasma insulin response to yoghurt type B

Postprandial glucose blood levels240 minutes post-ingestion

Postprandial glucose responses in blood upon a mixed meal challenge

Cholesterol concentrationBaseline

Fasting plasma cholesterol concentration

Postprandial blood glucose levels120 minutes post-ingestion

Postprandial glucose responses in blood upon an oral glucose tolerance test

Postprandial blood insulin levels120 minutes post-ingestion

Postprandial insulin responses in blood upon an oral glucose tolerance test

Postprandial gut hormone blood levels240 minutes post-ingestion

Postprandial gut hormone concentrations in blood upon a mixed meal challenge

HbA1cBaseline

HbA1c

PBMC compositionEnd of intervention (week 12)

Immune function as measured by PBMC composition

Short-term well-being4 hours post-ingestion

Short-term well-being upon investigational product consumption assessed by the Multidimensional Mood Questionnaire (MDMQ)

Postprandial fatty acid blood levels240 minutes post-ingestion

Postprandial fatty acid concentrations in blood upon a mixed meal challenge

Physical activityContinuous for 3 non-consecutive weeks between week 1 and week 9 of the dietary intervention

Continuous physical activity levels, measured by ActivPAL3 micro (PAL Technologies, Glasgow, Scotland) during 3 non-consecutive weeks

Liver fat contentBaseline

Liver fat content as measured by MRS

Fasting insulin concentrationBaseline

Fasting insulin concentration

Circulating cytokinesBaseline

Circulating plasma cytokines

Immune responseEnd of intervention (week 12)

Immune response upon TLR stimulation

Oxidative stress marker urineEnd of intervention (week 12)

Oxidative stress as measured by free 8-iso PGF2a in urine

Alpha-dicarbonyl concentrations bloodEnd of intervention (week 12)

alpha-dicarbonyl concentrations in plasma as measured by ultraperformance liquid chromatography-tandem mass spectrometry

Postprandial insulin blood levels240 minutes post-ingestion

Postprandial insulin responses in blood upon a mixed meal challenge

Postprandial metabolite blood levels240 minutes post-ingestion

Postprandial responses in blood upon a mixed meal challenge as measured by metabolomics

Postprandial lipid profiling240 minutes post-ingestion

Postprandial lipid profiling in blood upon a mixed meal challenge

Body fat distributionBaseline

Ratio between visceral and subcutaneous adipose tissue as measured by magnetic resonance imaging (MRI)

Metabolism immune cell populationsBaseline

Metabolism of immune cell populations as measured by SCENITH

Advanced glycation end-products (AGEs) bloodEnd of intervention (week 12)

AGE concentrations in plasma as measured by ultraperformance liquid chromatography-tandem mass spectrometry

Salivary amylase activityEnd of intervention (week 12)

Activity of salivary amylase

Plasma glucose response fries A2 hours post-ingestion

Plasma glucose response to fries type A

Plasma glucose response yoghurt B2 hours post-ingestion

Plasma glucose response to yoghurt type B

Immune functionEnd of intervention (week 12)

Metabolism of immune cell populations as measured by SCENITH

Cognitive performanceBaseline

Cognitive performance as measured by the Cambridge Neuropsychological Test Automated Battery

Genetic variation metabolism and responses to foodBaseline

SNPs in genes relevant for metabolism and responses to food, collected using a mouth swab

Plasma glucose response cake B2 hours post-ingestion

Plasma glucose response to cake type B

Oxidative stress in plasmaEnd of intervention (week 12)

Oxidative stress as measured by nitrotyrosine in plasma

Oral microbiota compositionWeek 9 dietary intervention

Microbiota composition in the saliva by extracting bacterial DNA for 16S rRNA sequencing

Self-reported stool consistencyWeek 9 dietary intervention

Self-reported stool consistency by using the bristol stool chart (scores between 1-7). Low scores indicate constipation and high scores diarrhea. Scores of 3-4 indicate a 'normal' stool.

Habitual dietary intakeBaseline

Habitual dietary intake assessment with a food frequency questionnaire (FFQ)

Plasma glucose response cake C2 hours post-ingestion

Plasma glucose response to cake type C

Plasma insulin response fries A2 hours post-ingestion

Plasma insulin response to fries type A

AGE accumulationEnd of intervention (week 12)

Accumulation of AGEs in the skin as measured by an AGE reader (Diagnoptics, Groningen, the Netherlands)

Fecal microbiota compositionWeek 9 dietary intervention

Microbiota composition in the feces by extracting bacterial DNA for 16S rRNA sequencing

Transit timeEnd of intervention (week 12)

Transit time, measured as the time in with blue (dietary) dye is consumed and observed in the feces

Salivary amylase concentrationEnd of intervention (week 12)

Concentration of salivary amylase

Plasma glucose response cake A2 hours post-ingestion

Plasma glucose response to cake type A

Plasma insulin response fries B2 hours post-ingestion

Plasma insulin response to fries type B

Plasma insulin response yoghurt A2 hours post-ingestion

Plasma insulin response to yoghurt type A

Plasma insulin response yoghurt C2 hours post-ingestion

Plasma insulin response to yoghurt type C

Genetic variation amylase genesBaseline

SNPs in genes coding for amylase, collected using a mouth swab

Plasma glucose response fries B2 hours post-ingestion

Plasma glucose response to fries type B

Plasma glucose response fries C2 hours post-ingestion

Plasma glucose response to fries type C

Plasma glucose response yoghurt A2 hours post-ingestion

Plasma glucose response to yoghurt type A

Plasma glucose response yoghurt C2 hours post-ingestion

Plasma glucose response to yoghurt type C

Plasma insulin response cake A2 hours post-ingestion

Plasma insulin response to cake type A

Plasma insulin response cake B2 hours post-ingestion

Plasma insulin response to cake type B

Plasma insulin response cake C2 hours post-ingestion

Plasma insulin response to cake type C

Trial Locations

Locations (1)

Wageningen University, Division of Human Nutrition

🇳🇱

Wageningen, Gelderland, Netherlands

Wageningen University, Division of Human Nutrition
🇳🇱Wageningen, Gelderland, Netherlands
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