Obesity & OverweightNCT07690176
How the Body Processes Sugar After Eating, in People With Different Body Weights
A study testing Low-glycemic breakfast (randomized vs high glycemic), High-glycaemic breakfast (randomized vs low glycemic) and High-glycaemic breakfast in people with Obesity & Overweight, run by Wageningen University at 1 site in Netherlands.
Trial summary
The goal of this clinical trial is to learn how a high-glycaemic meal affects the way the body processes glucose in healthy adults who are either lean or have obesity. The main questions it aims to answer are: Is the polyol pathway (conversion of glucose into sorbitol and fructose) more active after a hyperglycaemic… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity & Overweight
- What is being tested?
- Low-glycemic breakfast (randomized vs high glycemic), High-glycaemic breakfast (randomized vs low glycemic) and High-glycaemic breakfast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 24 Feb 2026to 30 Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy males and females using contraception during and for 3 months after the study.
- Aged from 18-65 years at the time of signing informed consent
- 18.5 < BMI < 25 kg·m2 or 30< BMI <35 kg·m2
- Must be willing and able to communicate and participate in the whole study, including consumption of 14C-glucose and meals offered during study conduct
- Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)
- Must usually eat 3 meals per day (i.e. breakfast, lunch and dinner)
Who cannot join
- Diabetes (Type 1, Type 2, or genetic form of diabetes)
- Any diagnosed cardiovascular (heart) disease or high blood pressure (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
- HbA1c higher than 53 mmol/mol
- History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastro-intestinal disease, immunodeficiency, endocrine, neurological, or psychiatric disorders
- Any diagnosed respiratory disease, such as COPD or asthma
- Any previous motor disorders or disorders in muscle and/or lipid metabolism
Show all 30Show fewer
- Known severe kidney problems
- Presence of an ulcer in the stomach or gut and/or strong history of indigestion
- Recent or chronic history of diarrhoea
- Known anaemia
- A personal or family history of thrombosis (clots), epilepsy, seizures, or schizophrenia.
- Regular use of dietary supplements (>3 times per week)
- Chronic use of any prescribed or over the counter pharmaceuticals (excluding oral contraceptives and contraceptive devices)
- History of any drug or alcohol abuse in the past two years
- A confirmed positive alcohol breath test at screening or admission
- Drug use
- Claustrophobia
- Subjects who are on a weight loss diet or following a high calorific/high protein diet to gain weight
- Subjects with functional constipation
- Any known food allergies or intolerances to the 14 major food allergens (celery, cereals containing gluten, crustaceans, eggs, fish, lupin, milk, molluscs, mustard, tree nuts, peanuts, sesame seeds, soybeans, sulphur dioxide and sulphites) or history of a malabsorption syndrome including coeliac disease
- Subjects who have regular gastrointestinal complaints including abdominal pain, stomach upsets and borborygmi or known or suspected irritable bowel syndrome
- Currently taking part in another scientific research
- Having received a product with 14C in the past 12 months
- Pregnant or breastfeeding
- Smoking or having used nicotine-containing products in the 6 months prior to the study.
- Subjects who have taken antibiotics within the 60 days prior to the adaptation period.
- Currently involved in a structured progressive resistance training programme (>3 times per week)
- Sedentary lifestyle as assessed using the International Physical Activity Questionnaire [IPAQ].
- Unable to give consent
- Employed or undertaking a thesis or internship at the department of Human and Animal Physiology
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Wageningen University and Research
Wageningen, 6708 WD
Ayesha Heinis, PhD, 0621578392, ayesha.heinis@wur.nl
Marlou Dirks, PhD, 0031317-484 136, marlou.dirks@wur.nl
About this study
Official title: The Metabolic Effects of a Hyperglycaemic Meal in Lean and Obese Individuals Using a [14C]-Glucose Microtracer Approach
The goal of this clinical trial is to learn how a high-glycaemic meal affects the way the body processes glucose in healthy adults who are either lean or have obesity. The main questions it aims to answer are: Is the polyol pathway (conversion of glucose into sorbitol and fructose) more active after a hyperglycaemic meal? Is this pathway more active in individuals with obesity compared with lean individuals? We will compare people who eat a high-glycaemic meal with those who eat a low-glycaemic meal to see whether meal type changes how glucose is metabolized in the body. Participants will drink a small amount of 14C-labelled glucose so researchers can trace how the body uses glucose, spend one long study day (about 12 hours in the lab) plus short morning visits on days 2 to 4, and undergo repeated measurements, including blood sampling, breath sampling, indirect calorimetry, and complete urine and stool collection for 72 hours. This information will help us understand how glucose is processed in the body and whether people with obesity handle glucose differently than lean individuals.
Read the detailed description
Obesity is associated with substantial metabolic dysregulation, including impaired glucose handling, increased oxidative stress, and altered nutrient partitioning. A metabolic pathway of particular interest in this context is the polyol pathway, in which glucose is converted to sorbitol by aldose reductase and subsequently to fructose. Preclinical studies suggest that flux through this pathway increases when intracellular glucose concentrations rise, such as during hyperglycaemia or insulin resistance. Greater activity of this pathway has been linked to the formation of advanced glycation end products, oxidative stress, and stimulation of de novo lipogenesis. These mechanisms have been proposed as contributors to metabolic complications commonly observed in individuals with obesity. Despite these findings from animal and in vitro studies, polyol pathway activity and its regulation by dietary glycaemic load have not been systematically quantified in humans. This clinical trial addresses this gap by applying a highly sensitive [14C]-glucose microtracer approach to measure the metabolic fate of glucose following ingestion of meals with differing glycaemic properties in lean individuals and individuals with obesity.
The study makes use of uniformly labelled [14C]-glucose, which allows tracing of glucose-derived carbon into metabolic intermediates, expired CO₂, urine, faeces, and lipids using Accelerator Mass Spectrometry. This technology enables quantification of metabolic products with extremely small isotope doses, resulting in radiation exposure far below natural background levels. Through this approach, the study can directly assess the extent to which ingested glucose is oxidized, converted into polyol pathway intermediates, incorporated into lipids, or excreted. The microtracer method provides a level of mechanistic resolution that cannot be achieved with stable isotopes or traditional metabolic tests.
The study design includes a single 72-hour metabolic test period during which participants consume either a high- or low-glycaemic breakfast depending on group allocation. The subsequent ingestion of [14C]-glucose allows tracking of postprandial metabolic routing under these two dietary conditions. Lean participants are randomized to either glycaemic condition, whereas individuals with obesity receive the high-glycaemic meal to address the study's main objective of comparing pathway activity between lean and obese phenotypes under hyperglycaemic challenge. Although the protocol includes multiple laboratory measurements, the aim of this Detailed Description is not to reproduce the procedure schedule, but to summarize the scientific characteristics of the design. In general terms, the study integrates whole-body, biochemical, and tissue-level metabolic assessments to characterize glucose metabolism in vivo.
Whole-body energy expenditure and substrate oxidation are measured repeatedly through indirect calorimetry to determine the proportion of glucose that is oxidized versus stored or redirected into other metabolic pathways. Breath samples are collected to quantify 14CO₂ production, which provides a sensitive measure of glucose oxidation and contributes to mass balance calculations. Serial blood sampling enables the measurement of plasma glucose, insulin, and the appearance of 14C-labelled metabolites, providing insight into the dynamics of glucose disposal and conversion to sorbitol, fructose, and downstream metabolites.
A distinctive feature of this study is the assessment of forearm arteriovenous metabolite balance, obtained from arterialized and deep-venous blood sampling combined with Doppler ultrasound measurement of forearm blood flow. This technique allows calculation of tissue-specific uptake and release of glucose and glucose-derived metabolites across skeletal muscle, a major site of postprandial glucose disposal. These measurements offer a physiologically meaningful index of muscle insulin sensitivity and provide additional perspective on how glycaemic load and obesity influence metabolic flux at the tissue level.
Collection of urine and faeces for 72 hours enables full recovery of the administered tracer, allowing detailed mass balance calculations. This information reveals how much of the ingested glucose is oxidized, excreted, or directed into biosynthetic pathways. By integrating data from breath, blood, urine, and faeces, the study can comprehensively map the metabolic fate of glucose and determine how this differs across physiological states.
The primary scientific questions addressed by this study are whether polyol pathway activity increases under hyperglycaemic conditions in humans and whether individuals with obesity demonstrate greater pathway activation than lean individuals. The study further explores the relationship between polyol pathway activation and de novo lipogenesis and evaluates whether the glycaemic load of a meal modulates these pathways. By combining microtracer-based flux analysis with whole-body and tissue-specific measurements, the study aims to provide mechanistic insight into early metabolic disturbances associated with obesity.
Overall, this trial will generate foundational human data on endogenous fructose production and glucose routing in response to dietary glycaemic load. These findings may contribute to improved understanding of how carbohydrate metabolism becomes dysregulated in obesity and may support the development of nutritional or therapeutic strategies targeting glucose-handling pathways. The study also demonstrates the potential of Accelerator Mass Spectrometry as a powerful tool for investigating nutrient metabolism in vivo with minimal participant burden and extremely low radiation exposure.
- Conditions
- Obesity & Overweight
- Being tested
- Low-glycemic breakfast (randomized vs high glycemic), High-glycaemic breakfast (randomized vs low glycemic), High-glycaemic breakfast
- Keywords
- Hyperglycaemic meal, 14C-glucose, microtracer, accelerator mass spectrometry, polyol pathway, de novo lipogenesis, arteriovenous forearm balance
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-glycemic breakfast (randomized vs high glycemic)Dietary supplement
Participants receive a single oral microtracer dose of [14C] glucose (≤10 kBq / 270 nCi) mixed with 1 g unlabeled glucose, administered immediately after a low glycemic breakfast. The dose is prepared fresh on the morning of administration and consumed as a liquid drink. This approach enables tracing of glucose metabolism using Accelerator Mass Spectrometry (AMS) at extremely low radiation exposure (~0.006 mSv). The intervention is combined with indirect calorimetry, serial blood sampling (including arterialized and deep-venous lines), expired air collection for 14CO₂ recovery, and pooled urine/feces collection over 72 hours to quantify metabolic fate and pathway activity.
High-glycaemic breakfast (randomized vs low glycemic)Dietary supplement
Participants receive a single oral microtracer dose of [14C] glucose (≤10 kBq / 270 nCi) mixed with 1 g unlabeled glucose, administered immediately after a high glycemic breakfast. The dose is prepared fresh on the morning of administration and consumed as a liquid drink. This approach enables tracing of glucose metabolism using Accelerator Mass Spectrometry (AMS) at extremely low radiation exposure (~0.006 mSv). The intervention is combined with indirect calorimetry, serial blood sampling (including arterialized and deep-venous lines), expired air collection for 14CO₂ recovery, and pooled urine/feces collection over 72 hours to quantify metabolic fate and pathway activity.
High-glycaemic breakfastDietary supplement
Participants receive a single oral microtracer dose of [14C] glucose (≤10 kBq / 270 nCi) mixed with 1 g unlabeled glucose, administered immediately after a high glycemic breakfast. The dose is prepared fresh on the morning of administration and consumed as a liquid drink. This approach enables tracing of glucose metabolism using Accelerator Mass Spectrometry (AMS) at extremely low radiation exposure (~0.006 mSv). The intervention is combined with indirect calorimetry, serial blood sampling (including arterialized and deep-venous lines), expired air collection for 14CO₂ recovery, and pooled urine/feces collection over 72 hours to quantify metabolic fate and pathway activity.
| Study group | Role | What they receive |
|---|---|---|
| A - Lean individuals (Low-glycemic breakfast) | Experimental | Lean participants randomized to consume a low-glycemic breakfast prior to administration of an oral [¹⁴C]-glucose microtracer to assess postprandial glucose metabolism. Receives: Dietary Supplement: Low-glycemic breakfast (randomized vs high glycemic) |
| B - Lean individuals (High-glycemic breakfast) | Experimental | Lean participants randomized to consume a high-glycemic breakfast prior to administration of an oral [¹⁴C]-glucose microtracer to assess postprandial glucose metabolism. Receives: Dietary Supplement: High-glycaemic breakfast (randomized vs low glycemic) |
| C - Individuals with obesity (High-glycemic breakfast) | Experimental | Participants with obesity consume a high-glycemic breakfast prior to administration of an oral [¹⁴C]-glucose microtracer to assess postprandial glucose metabolism. Receives: Dietary Supplement: High-glycaemic breakfast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total mass balance (cumulative recovery of 14C)
Cumulative recovery of total radioactivity across all excreta (urine, faeces, and expired CO₂) expressed as percentage of the administered dose.
Measured: Baseline to 72 hours post dose
Secondary outcomes (10)
Polyol pathway activity (fructose-to-glucose ratio)
Ratio of 14C-fructose to 14C-glucose concentrations
Measured: Baseline to 72 hours post 14C ingestion
Polyol pathway activity (sorbitol-to-glucose ratio)
Ratio of 14C-sorbitol to 14C-glucose concentrations
Measured: Baseline to 72 hours post 14C ingestion
Polyol pathway activity (AUC-based ratio)
Ratio of area under the curve (AUC) for 14C-fructose to AUC for 14C-glucose
Measured: Baseline to 72 hours post 14C ingestion
De novo lipogenesis from glucose
Incorporation of 14C label into plasma lipids as a measure of fatty acid synthesis from glucose
Measured: Baseline to 72 hours
Caloric value of glucose
Recovery of 14C label in expired CO2 and excreta, expressed as a measure of energy yield of ingested glucose
Measured: Baseline to 72 hours
Forearm arteriovenous balance of 14C-glucose and metabolites
Arteriovenous concentration differences of 14C-glucose and metabolites across the forearm, combined with blood flow measurements
Measured: 0-240 minutes post dose
14C-labelled metabolites in carbohydrate metabolism pathways
Concentrations and 14C-enrichment of glucose, fructose, and related metabolites in plasma and erythrocytes.
Measured: Baseline to 72 hours post 14C ingestion
Carbohydrate oxidation
Carbohydrate oxidation rate measured using indirect calorimetry and calculated according to standard equations under fasted and postprandial conditions following ingestion of a high- or low-glycaemic meal.
Measured: Baseline to 72 hours
Lipid oxidation
Lipid oxidation rate measured using indirect calorimetry and calculated according to standard equations under fasted and postprandial conditions following ingestion of a high- or low-glycaemic meal.
Measured: Baseline to 72 hours
Energy expenditure
Total energy expenditure measured using indirect calorimetry and calculated according to standard equations under fasted and postprandial conditions following ingestion of a high- or low-glycaemic meal.
Measured: Baseline to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start24 Feb 2026
- Primary completion30 Jul 2026 (estimated)
- Study completion30 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Obesity & OverweightStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-centre, open-label, parallel assignment with three arms. Lean participants are randomized to receive either a low-glycaemic or high-glycaemic breakfast; obese participants receive a high-glycaemic breakfast (non-randomized). All participants ingest a microtracer dose of \[14C\]-glucose (≤10 kBq/270 nCi) immediately after breakfast to enable metabolic tracing via accelerator mass spectrometry (AMS). The study includes repeated indirect calorimetry, serial blood sampling (including forearm arteriovenous balance), expired air collection, and 72-hour urine and feces collection to assess polyol pathway activity, de novo lipogenesis, and energy metabolism.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wageningen University
- Sponsor type
- University, hospital or other
- Collaborators
- Bonumose, Inc., TNO
- Responsible party
- Principal investigator, Marlou Dirks, Wageningen University
- Investigators
- Marlou Dirks, PhD, Principal investigator, Wageningen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07690176
- Sponsor's protocol ID
- NL85522.028.24
- Status last verified
- Apr 2026
- First submitted
- 17 Apr 2026
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared outside the study team.
Publications
Kruszynska YT, Mulford MI, Yu JG, Armstrong DA, Olefsky JM. Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion. Diabetes. 1997 Oct;46(10):1586-93. doi: 10.2337/diacare.46.10.1586.
PubMed 9313754Fery F, d'Attellis NP, Balasse EO. Mechanisms of starvation diabetes: a study with double tracer and indirect calorimetry. Am J Physiol. 1990 Dec;259(6 Pt 1):E770-7. doi: 10.1152/ajpendo.1990.259.6.E770.
PubMed 2260646Moseley L, Jentjens RL, Waring RH, Harris RM, Harding LK, Jeukendrup AE. Measurement of exogenous carbohydrate oxidation: a comparison of [U-14C]glucose and [U-13C]glucose tracers. Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E206-11. doi: 10.1152/ajpendo.00423.2004. Epub 2005 Feb 22.
PubMed 15727950Wisneski JA, Gertz EW, Neese RA, Gruenke LD, Craig JC. Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia. J Am Coll Cardiol. 1985 May;5(5):1138-46. doi: 10.1016/s0735-1097(85)80016-4.
PubMed 3989125Virkamaki A, Puhakainen I, Nurjhan N, Gerich JE, Yki-Jarvinen H. Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans. Am J Physiol. 1990 Sep;259(3 Pt 1):E397-404. doi: 10.1152/ajpendo.1990.259.3.E397.
PubMed 2205108Bell PM, Firth RG, Rizza RA. Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used. J Clin Invest. 1986 Dec;78(6):1479-86. doi: 10.1172/JCI112739.
PubMed 3537009McMahon MM, Schwenk WF, Haymond MW, Rizza RA. Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans. Diabetes. 1989 Jan;38(1):97-107. doi: 10.2337/diab.38.1.97.
PubMed 2642438Katz H, Homan M, Butler P, Rizza R. Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans. Am J Physiol. 1992 Jul;263(1 Pt 1):E17-22. doi: 10.1152/ajpendo.1992.263.1.E17.
PubMed 1636695Ferrannini E, Bjorkman O, Reichard GA Jr, Pilo A, Olsson M, Wahren J, DeFronzo RA. The disposal of an oral glucose load in healthy subjects. A quantitative study. Diabetes. 1985 Jun;34(6):580-8. doi: 10.2337/diab.34.6.580.
PubMed 3891471Gallen IW, Macdonald IA. Effect of two methods of hand heating on body temperature, forearm blood flow, and deep venous oxygen saturation. Am J Physiol. 1990 Nov;259(5 Pt 1):E639-43. doi: 10.1152/ajpendo.1990.259.5.E639.
PubMed 2240202ANDRES R, ZIERLER KL, ANDERSON HM, STAINSBY WN, CADER G, GHRAYYIB AS, LILIENTHAL JL Jr. Measurement of blood flow and volume in the forearm of man; with notes on the theory of indicator-dilution and on production of turbulence, hemolysis, and vasodilatation by intra-vascular injection. J Clin Invest. 1954 Apr;33(4):482-504. doi: 10.1172/JCI102919. No abstract available.
PubMed 13152188Dirks ML, Wall BT, Otten B, Cruz AM, Dunlop MV, Barker AR, Stephens FB. High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz049. doi: 10.1210/clinem/dgz049.
PubMed 31609422Batchuluun B, Pinkosky SL, Steinberg GR. Lipogenesis inhibitors: therapeutic opportunities and challenges. Nat Rev Drug Discov. 2022 Apr;21(4):283-305. doi: 10.1038/s41573-021-00367-2. Epub 2022 Jan 14.
PubMed 35031766Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014 Mar;146(3):726-35. doi: 10.1053/j.gastro.2013.11.049. Epub 2013 Dec 4.
PubMed 24316260Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005 May;115(5):1343-51. doi: 10.1172/JCI23621.
PubMed 15864352
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Metabolic Effects of a Hyperglycaemic Meal in Lean and Obese Individuals Using a [14C]-Glucose Microtracer Approach
- ClinicalTrials.gov ID
- NCT07690176
- Acronym / sponsor ID
- NL85522.028.24
- Conditions
- Obesity & Overweight
- Keywords
- Hyperglycaemic meal, 14C-glucose, microtracer, accelerator mass spectrometry, polyol pathway, de novo lipogenesis, arteriovenous forearm balance
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Wageningen UniversityUniversity, hospital or other
- Collaborators
- Bonumose, Inc., TNO
- Study start
- 24 Feb 2026 (actual)
- Primary completion
- 30 Jul 2026 (estimated)
- Study completion
- 30 Jul 2026 (estimated)
- First posted
- 8 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn how a high-glycaemic meal affects the way the body processes glucose in healthy adults who are either lean or have obesity. The main questions it aims to answer are: Is the polyol pathway (conversion of glucose into sorbitol and fructose) more active after a hyperglycaemic meal? Is this pathway more active in individuals with obesity compared with lean individuals? We will compare people who eat a high-glycaemic meal with those who eat a low-glycaemic meal to see whether meal type changes how glucose is metabolized in the body. Participants will drink a small amount of 14C-labelled glucose so researchers can trace how the body uses glucose, spend one long study day (about 12 hours in the lab) plus short morning visits on days 2 to 4, and undergo repeated measurements, including blood sampling, breath sampling, indirect calorimetry, and complete urine and stool collection for 72 hours. This information will help us understand how glucose is processed in the body and whether people with obesity handle glucose differently than lean individuals.
Detailed description
Obesity is associated with substantial metabolic dysregulation, including impaired glucose handling, increased oxidative stress, and altered nutrient partitioning. A metabolic pathway of particular interest in this context is the polyol pathway, in which glucose is converted to sorbitol by aldose reductase and subsequently to fructose. Preclinical studies suggest that flux through this pathway increases when intracellular glucose concentrations rise, such as during hyperglycaemia or insulin resistance. Greater activity of this pathway has been linked to the formation of advanced glycation end products, oxidative stress, and stimulation of de novo lipogenesis. These mechanisms have been proposed as contributors to metabolic complications commonly observed in individuals with obesity. Despite these findings from animal and in vitro studies, polyol pathway activity and its regulation by dietary glycaemic load have not been systematically quantified in humans. This clinical trial addresses this gap by applying a highly sensitive [14C]-glucose microtracer approach to measure the metabolic fate of glucose following ingestion of meals with differing glycaemic properties in lean individuals and individuals with obesity.
The study makes use of uniformly labelled [14C]-glucose, which allows tracing of glucose-derived carbon into metabolic intermediates, expired CO₂, urine, faeces, and lipids using Accelerator Mass Spectrometry. This technology enables quantification of metabolic products with extremely small isotope doses, resulting in radiation exposure far below natural background levels. Through this approach, the study can directly assess the extent to which ingested glucose is oxidized, converted into polyol pathway intermediates, incorporated into lipids, or excreted. The microtracer method provides a level of mechanistic resolution that cannot be achieved with stable isotopes or traditional metabolic tests.
The study design includes a single 72-hour metabolic test period during which participants consume either a high- or low-glycaemic breakfast depending on group allocation. The subsequent ingestion of [14C]-glucose allows tracking of postprandial metabolic routing under these two dietary conditions. Lean participants are randomized to either glycaemic condition, whereas individuals with obesity receive the high-glycaemic meal to address the study's main objective of comparing pathway activity between lean and obese phenotypes under hyperglycaemic challenge. Although the protocol includes multiple laboratory measurements, the aim of this Detailed Description is not to reproduce the procedure schedule, but to summarize the scientific characteristics of the design. In general terms, the study integrates whole-body, biochemical, and tissue-level metabolic assessments to characterize glucose metabolism in vivo.
Whole-body energy expenditure and substrate oxidation are measured repeatedly through indirect calorimetry to determine the proportion of glucose that is oxidized versus stored or redirected into other metabolic pathways. Breath samples are collected to quantify 14CO₂ production, which provides a sensitive measure of glucose oxidation and contributes to mass balance calculations. Serial blood sampling enables the measurement of plasma glucose, insulin, and the appearance of 14C-labelled metabolites, providing insight into the dynamics of glucose disposal and conversion to sorbitol, fructose, and downstream metabolites.
A distinctive feature of this study is the assessment of forearm arteriovenous metabolite balance, obtained from arterialized and deep-venous blood sampling combined with Doppler ultrasound measurement of forearm blood flow. This technique allows calculation of tissue-specific uptake and release of glucose and glucose-derived metabolites across skeletal muscle, a major site of postprandial glucose disposal. These measurements offer a physiologically meaningful index of muscle insulin sensitivity and provide additional perspective on how glycaemic load and obesity influence metabolic flux at the tissue level.
Collection of urine and faeces for 72 hours enables full recovery of the administered tracer, allowing detailed mass balance calculations. This information reveals how much of the ingested glucose is oxidized, excreted, or directed into biosynthetic pathways. By integrating data from breath, blood, urine, and faeces, the study can comprehensively map the metabolic fate of glucose and determine how this differs across physiological states.
The primary scientific questions addressed by this study are whether polyol pathway activity increases under hyperglycaemic conditions in humans and whether individuals with obesity demonstrate greater pathway activation than lean individuals. The study further explores the relationship between polyol pathway activation and de novo lipogenesis and evaluates whether the glycaemic load of a meal modulates these pathways. By combining microtracer-based flux analysis with whole-body and tissue-specific measurements, the study aims to provide mechanistic insight into early metabolic disturbances associated with obesity.
Overall, this trial will generate foundational human data on endogenous fructose production and glucose routing in response to dietary glycaemic load. These findings may contribute to improved understanding of how carbohydrate metabolism becomes dysregulated in obesity and may support the development of nutritional or therapeutic strategies targeting glucose-handling pathways. The study also demonstrates the potential of Accelerator Mass Spectrometry as a powerful tool for investigating nutrient metabolism in vivo with minimal participant burden and extremely low radiation exposure.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Single-centre, open-label, parallel assignment with three arms. Lean participants are randomized to receive either a low-glycaemic or high-glycaemic breakfast; obese participants receive a high-glycaemic breakfast (non-randomized). All participants ingest a microtracer dose of [14C]-glucose (≤10 kBq/270 nCi) immediately after breakfast to enable metabolic tracing via accelerator mass spectrometry (AMS). The study includes repeated indirect calorimetry, serial blood sampling (including forearm arteriovenous balance), expired air collection, and 72-hour urine and feces collection to assess polyol pathway activity, de novo lipogenesis, and energy metabolism.
| Arm | Type | Receives |
|---|---|---|
| A - Lean individuals (Low-glycemic breakfast) | Experimental | Dietary Supplement: Low-glycemic breakfast (randomized vs high glycemic)Lean participants randomized to consume a low-glycemic breakfast prior to administration of an oral [¹⁴C]-glucose microtracer to assess postprandial glucose metabolism. |
| B - Lean individuals (High-glycemic breakfast) | Experimental | Dietary Supplement: High-glycaemic breakfast (randomized vs low glycemic)Lean participants randomized to consume a high-glycemic breakfast prior to administration of an oral [¹⁴C]-glucose microtracer to assess postprandial glucose metabolism. |
| C - Individuals with obesity (High-glycemic breakfast) | Experimental | Dietary Supplement: High-glycaemic breakfastParticipants with obesity consume a high-glycemic breakfast prior to administration of an oral [¹⁴C]-glucose microtracer to assess postprandial glucose metabolism. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy males and females using contraception during and for 3 months after the study.
- Aged from 18-65 years at the time of signing informed consent
- 18.5 < BMI < 25 kg·m2 or 30< BMI <35 kg·m2
- Must be willing and able to communicate and participate in the whole study, including consumption of 14C-glucose and meals offered during study conduct
- Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)
Key exclusion criteria (30 listed)
- Diabetes (Type 1, Type 2, or genetic form of diabetes)
- Any diagnosed cardiovascular (heart) disease or high blood pressure (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
- HbA1c higher than 53 mmol/mol
- History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastro-intestinal disease, immunodeficiency, endocrine, neurological, or psychiatric disorders
- Any diagnosed respiratory disease, such as COPD or asthma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-glycemic breakfast (randomized vs high glycemic)Participants receive a single oral microtracer dose of [14C] glucose (≤10 kBq / 270 nCi) mixed with 1 g unlabeled glucose, administered immediately after a low glycemic breakfast. The dose is prepared fresh on the morning of administration and consumed as a liquid drink. This approach enables tracing of glucose metabolism using Accelerator Mass Spectrometry (AMS) at extremely low radiation exposure (~0.006 mSv). The intervention is combined with indirect calorimetry, serial blood sampling (including arterialized and deep-venous lines), expired air collection for 14CO₂ recovery, and pooled urine/feces collection over 72 hours to quantify metabolic fate and pathway activity. | Dietary supplement | A - Lean individuals (Low-glycemic breakfast) |
| High-glycaemic breakfast (randomized vs low glycemic)Participants receive a single oral microtracer dose of [14C] glucose (≤10 kBq / 270 nCi) mixed with 1 g unlabeled glucose, administered immediately after a high glycemic breakfast. The dose is prepared fresh on the morning of administration and consumed as a liquid drink. This approach enables tracing of glucose metabolism using Accelerator Mass Spectrometry (AMS) at extremely low radiation exposure (~0.006 mSv). The intervention is combined with indirect calorimetry, serial blood sampling (including arterialized and deep-venous lines), expired air collection for 14CO₂ recovery, and pooled urine/feces collection over 72 hours to quantify metabolic fate and pathway activity. | Dietary supplement | B - Lean individuals (High-glycemic breakfast) |
| High-glycaemic breakfastParticipants receive a single oral microtracer dose of [14C] glucose (≤10 kBq / 270 nCi) mixed with 1 g unlabeled glucose, administered immediately after a high glycemic breakfast. The dose is prepared fresh on the morning of administration and consumed as a liquid drink. This approach enables tracing of glucose metabolism using Accelerator Mass Spectrometry (AMS) at extremely low radiation exposure (~0.006 mSv). The intervention is combined with indirect calorimetry, serial blood sampling (including arterialized and deep-venous lines), expired air collection for 14CO₂ recovery, and pooled urine/feces collection over 72 hours to quantify metabolic fate and pathway activity. | Dietary supplement | C - Individuals with obesity (High-glycemic breakfast) |
Primary outcome
Total mass balance (cumulative recovery of 14C)
Time frame: Baseline to 72 hours post dose
Cumulative recovery of total radioactivity across all excreta (urine, faeces, and expired CO₂) expressed as percentage of the administered dose.
10 secondary outcomes
Polyol pathway activity (fructose-to-glucose ratio)
Time frame: Baseline to 72 hours post 14C ingestion
Polyol pathway activity (sorbitol-to-glucose ratio)
Time frame: Baseline to 72 hours post 14C ingestion
Polyol pathway activity (AUC-based ratio)
Time frame: Baseline to 72 hours post 14C ingestion
De novo lipogenesis from glucose
Time frame: Baseline to 72 hours
Caloric value of glucose
Time frame: Baseline to 72 hours
Forearm arteriovenous balance of 14C-glucose and metabolites
Time frame: 0-240 minutes post dose
14C-labelled metabolites in carbohydrate metabolism pathways
Time frame: Baseline to 72 hours post 14C ingestion
Carbohydrate oxidation
Time frame: Baseline to 72 hours
Lipid oxidation
Time frame: Baseline to 72 hours
Energy expenditure
Time frame: Baseline to 72 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Results publication: PubMed 9313754Kruszynska YT, Mulford MI, Yu JG, Armstrong DA, Olefsky JM. Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion. Diabetes. 1997 Oct;46(10):1586-93. doi: 10.2337/diacare.46.10.1586.
- Results publication: PubMed 2260646Fery F, d'Attellis NP, Balasse EO. Mechanisms of starvation diabetes: a study with double tracer and indirect calorimetry. Am J Physiol. 1990 Dec;259(6 Pt 1):E770-7. doi: 10.1152/ajpendo.1990.259.6.E770.
- Results publication: PubMed 15727950Moseley L, Jentjens RL, Waring RH, Harris RM, Harding LK, Jeukendrup AE. Measurement of exogenous carbohydrate oxidation: a comparison of [U-14C]glucose and [U-13C]glucose tracers. Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E206-11. doi: 10.1152/ajpendo.00423.2004. Epub 2005 Feb 22.
- Results publication: PubMed 3989125Wisneski JA, Gertz EW, Neese RA, Gruenke LD, Craig JC. Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia. J Am Coll Cardiol. 1985 May;5(5):1138-46. doi: 10.1016/s0735-1097(85)80016-4.
- Results publication: PubMed 2205108Virkamaki A, Puhakainen I, Nurjhan N, Gerich JE, Yki-Jarvinen H. Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans. Am J Physiol. 1990 Sep;259(3 Pt 1):E397-404. doi: 10.1152/ajpendo.1990.259.3.E397.
- Results publication: PubMed 3537009Bell PM, Firth RG, Rizza RA. Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used. J Clin Invest. 1986 Dec;78(6):1479-86. doi: 10.1172/JCI112739.
- Results publication: PubMed 2642438McMahon MM, Schwenk WF, Haymond MW, Rizza RA. Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans. Diabetes. 1989 Jan;38(1):97-107. doi: 10.2337/diab.38.1.97.
- Results publication: PubMed 1636695Katz H, Homan M, Butler P, Rizza R. Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans. Am J Physiol. 1992 Jul;263(1 Pt 1):E17-22. doi: 10.1152/ajpendo.1992.263.1.E17.
- Results publication: PubMed 3891471Ferrannini E, Bjorkman O, Reichard GA Jr, Pilo A, Olsson M, Wahren J, DeFronzo RA. The disposal of an oral glucose load in healthy subjects. A quantitative study. Diabetes. 1985 Jun;34(6):580-8. doi: 10.2337/diab.34.6.580.
- Results publication: PubMed 2240202Gallen IW, Macdonald IA. Effect of two methods of hand heating on body temperature, forearm blood flow, and deep venous oxygen saturation. Am J Physiol. 1990 Nov;259(5 Pt 1):E639-43. doi: 10.1152/ajpendo.1990.259.5.E639.
- Results publication: PubMed 13152188ANDRES R, ZIERLER KL, ANDERSON HM, STAINSBY WN, CADER G, GHRAYYIB AS, LILIENTHAL JL Jr. Measurement of blood flow and volume in the forearm of man; with notes on the theory of indicator-dilution and on production of turbulence, hemolysis, and vasodilatation by intra-vascular injection. J Clin Invest. 1954 Apr;33(4):482-504. doi: 10.1172/JCI102919. No abstract available.
- Results publication: PubMed 31609422Dirks ML, Wall BT, Otten B, Cruz AM, Dunlop MV, Barker AR, Stephens FB. High-fat Overfeeding Does Not Exacerbate Rapid Changes in Forearm Glucose and Fatty Acid Balance During Immobilization. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz049. doi: 10.1210/clinem/dgz049.
- Individual participant dataSharing planned: No. Individual participant data will not be shared outside the study team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marlou Dirks, PhD principal investigator
Wageningen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-glycemic breakfast (randomized vs high glycemic), High-glycaemic breakfast (randomized vs low glycemic) and High-glycaemic breakfast in people with Obesity & Overweight, run by Wageningen University at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marlou Dirks, PhD (+31 317-484 136, Marlou.Dirks@wur.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total mass balance (cumulative recovery of 14C) (time frame: Baseline to 72 hours post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07690176, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.