Insulin ResistanceNCT05743868
Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes
A study testing Standardized Dinner and Premeal exercise in people with Insulin Resistance and Hypertriglyceridemia, run by Yale University at 1 site in Netherlands.
Trial summary
The focus of this cross-sectional study is to determine the effects of tissue-specific (adipose tissue or muscle) vs global (combined) insulin resistance (IR) on hepatic triglyceride biosynthesis in humans, and to determine differential effects of an acute exercise intervention on hepatic triglyceride biosynthesis in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Insulin Resistance, Hypertriglyceridemia
- What is being tested?
- Standardized Dinner and Premeal exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNetherlands
- Study dates
- 16 Nov 2023to 24 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to give informed consent
- Overweight, defined as BMI 25-30 kg/m2
- Modest hypertriglyceridemia, defined as fasting plasma triglycerides 1.5-3.0mM
- High risk of insulin resistance, defined as fasting plasma insulin >64pM
- Stable weight for at least 3mo prior to participation
Who cannot join
- Active or chronic liver disease, kidney disease, congestive heart failure, unstable angina, history of acute cardiovascular events within 6mo of screening, history of seizures or syncope, or an active infection requiring antimicrobial therapy;
- Use of insulin, thiazolidinediones, SGLT2 inhibitors, or sulfonylureas;
- Use of fibrates, omega 3 (fish oil), niacin, or PCSK9 antagonists;
- Use of systemic glucocorticoids within 60d prior to participation;
- Hematocrit <35%;
- Pregnancy of breastfeeding;
- Active tobacco use, excessive alcohol intake (>14U/wk), or history of drug abuse.
Trial locations and contacts
1 site in 1 country.
About this study
The focus of this cross-sectional study is to determine the effects of tissue-specific (adipose tissue or muscle) vs global (combined) insulin resistance (IR) on hepatic triglyceride biosynthesis in humans, and to determine differential effects of an acute exercise intervention on hepatic triglyceride biosynthesis in these groups.
Read the detailed description
Hypothesis: Patients who primarily have muscle IR will have a greater percentage of lipids derived from de novo lipogenesis (DNL) than patients with combined muscle and adipose IR, and these subjects will respond more robustly to the effects of premeal exercise.
With this study, the investigators will demonstrate that the mechanisms that drive triglyceride overproduction in insulin-resistant humans are dependent on which tissues are insulin resistant. To this end, investigators will determine whether subjects with muscle insulin resistance and adipose tissue insulin resistance utilize different mechanisms of triglyceride biosynthesis to assemble hepatic very low density lipoprotein (VLDL), as compared with individuals with muscle insulin resistance but relative adipose tissue insulin sensitivity. Additionally, investigators will see if adipose tissue insulin sensitivity predicts exercise responsiveness of hepatic triglyceride production.
Main study parameters/endpoints: Difference in %DNL between subjects with global vs muscle-only insulin resistance as well as the differential effects of premeal exercise on %DNL in these groups.
- Conditions
- Insulin Resistance, Hypertriglyceridemia
- Being tested
- Standardized Dinner, Premeal exercise
- Medical subject headings
- Insulin Resistance, Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standardized DinnerBehavioural
De novo lipogenesis (DNL) will be assessed in all participants with a standardized dinner
Premeal exerciseBehavioural
DNL will be assessed in all participants with short bouts of premeal exercise with a standardized dinner
| Study group | Role | What they receive |
|---|---|---|
| IR participants with standardized dinner | Experimental | Participants with global IR and tissue-specific IR. Participants with global IR (in both skeletal muscle and adipose tissue) and tissue-specific IR (in adipose tissue). Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention.
Contribution of DNL to hepatic VLDL will be measured using a deuterated water drink, to be ingested prior to the standardized dinner. Blood will be drawn the following morning for the measurement of deuterium incorporation into triglycerides. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed. Receives: Behavioral: Standardized Dinner |
| IR participants with standardized dinner and premeal exercise | Experimental | Participants with global IR and tissue-specific IR. Participants with global IR (in both skeletal muscle and adipose tissue) and tissue-specific IR (in adipose tissue). Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention.
DNL will be assessed in all participants after a single day with short bouts of premeal exercise with a standardized dinner.
Contribution of DNL to hepatic VLDL will be measured using a deuterated water drink, to be ingested prior to the standardized dinner. Blood will be drawn the following morning for the measurement of deuterium incorporation into triglycerides. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed. Receives: Behavioral: Standardized Dinner; Behavioral: Premeal exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of tissue-specific insulin resistance on contribution of DNL to plasma triglyceride
The amount of de novo lipogenesis (DNL) in VLDL-triglycerides after a standard meal will be measured in plasma from whole blood. Relationship between DNL and 1) whole body (skeletal muscle) insulin resistance and 2) white adipose tissue insulin resistance will be assessed individually.
Measured: Baseline
Change in DNL in VLDL-triglycerides after a standard meal compared to a standard meal with premeal exercise.
The amount of de novo lipogenesis (DNL) in VLDL-triglycerides after a standard meal vs after a standard meal with premeal exercise will be measured in plasma from whole blood.
Measured: study visit 1 and study visit 2, up to 8 weeks
Secondary outcomes (4)
Change in plasma triglycerides after a standard meal compared to a standard meal with premeal exercise
Plasma triglycerides will be measured under both conditions.
Measured: study visit 1 and study visit 2, up to 8 weeks
Baseline plasma triglycerides
Plasma triglycerides will be measured at the screening visit to determine eligibility for the study
Measured: baseline
Adipose insulin sensitivity
Both nonesterified fatty acids and insulin will be measured in the plasma at baseline to calculate Adipo-IR, a measure of adipose tissue insulin sensitivity.
Measured: Baseline
Skeletal muscle/whole-body insulin sensitivity assessed by oral glucose tolerance test (OGTT)
Matsuda index will be used to evaluate whole body physiological insulin sensitivity from the data obtained by OGTT. Insulin sensitivity as calculated by the Matsuda index: [10,000 / √glucose minute 0 x insulin minute 0) (mean glucose (OGTT) x mean insulin OGTT)]. A higher result indicates less IR.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2023
- Study start16 Nov 2023
- Primary completion24 Jun 2026
- Study completion24 Jun 2026
Why it stopped: Poor accrual and lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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
- Crossover
- Model description
- Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed. Randomized crossover within group design.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Daniel F Vatner, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05743868
- Sponsor's protocol ID
- Vatner 012523
- Other IDs
- NL83166.018.22, R01DK124272
- Status last verified
- Oct 2026
- First submitted
- 15 Feb 2023
- Last updated
- 27 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: By reasonable request, PI can be reached by email, and individual participant data (OGTT results, fasting plasma data, DNL data) will be provided electronically.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes
- ClinicalTrials.gov ID
- NCT05743868
- Acronym / sponsor ID
- Vatner 012523
- Conditions
- Insulin Resistance, Hypertriglyceridemia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual and lack of funding
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Amsterdam UMC, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 16 Nov 2023 (actual)
- Primary completion
- 24 Jun 2026 (actual)
- Study completion
- 24 Jun 2026 (actual)
- First posted
- 24 Feb 2023 (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 focus of this cross-sectional study is to determine the effects of tissue-specific (adipose tissue or muscle) vs global (combined) insulin resistance (IR) on hepatic triglyceride biosynthesis in humans, and to determine differential effects of an acute exercise intervention on hepatic triglyceride biosynthesis in these groups.
Detailed description
Hypothesis: Patients who primarily have muscle IR will have a greater percentage of lipids derived from de novo lipogenesis (DNL) than patients with combined muscle and adipose IR, and these subjects will respond more robustly to the effects of premeal exercise.
With this study, the investigators will demonstrate that the mechanisms that drive triglyceride overproduction in insulin-resistant humans are dependent on which tissues are insulin resistant. To this end, investigators will determine whether subjects with muscle insulin resistance and adipose tissue insulin resistance utilize different mechanisms of triglyceride biosynthesis to assemble hepatic very low density lipoprotein (VLDL), as compared with individuals with muscle insulin resistance but relative adipose tissue insulin sensitivity. Additionally, investigators will see if adipose tissue insulin sensitivity predicts exercise responsiveness of hepatic triglyceride production.
Main study parameters/endpoints: Difference in %DNL between subjects with global vs muscle-only insulin resistance as well as the differential effects of premeal exercise on %DNL in these groups.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed. Randomized crossover within group design.
| Arm | Type | Receives |
|---|---|---|
| IR participants with standardized dinner | Experimental | Behavioral: Standardized DinnerParticipants with global IR and tissue-specific IR. Participants with global IR (in both skeletal muscle and adipose tissue) and tissue-specific IR (in adipose tissue). Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention. Contribution of DNL to hepatic VLDL will be measured using a deuterated water drink, to be ingested prior to the standardized dinner. Blood will be drawn the following morning for the measurement of deuterium incorporation into triglycerides. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed. |
| IR participants with standardized dinner and premeal exercise | Experimental | Behavioral: Standardized Dinner, Behavioral: Premeal exerciseParticipants with global IR and tissue-specific IR. Participants with global IR (in both skeletal muscle and adipose tissue) and tissue-specific IR (in adipose tissue). Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention. DNL will be assessed in all participants after a single day with short bouts of premeal exercise with a standardized dinner. Contribution of DNL to hepatic VLDL will be measured using a deuterated water drink, to be ingested prior to the standardized dinner. Blood will be drawn the following morning for the measurement of deuterium incorporation into triglycerides. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Ability to give informed consent
- Overweight, defined as BMI 25-30 kg/m2
- Modest hypertriglyceridemia, defined as fasting plasma triglycerides 1.5-3.0mM
- High risk of insulin resistance, defined as fasting plasma insulin >64pM
- Stable weight for at least 3mo prior to participation
Key exclusion criteria (7 listed)
- Active or chronic liver disease, kidney disease, congestive heart failure, unstable angina, history of acute cardiovascular events within 6mo of screening, history of seizures or syncope, or an active infection requiring antimicrobial therapy;
- Use of insulin, thiazolidinediones, SGLT2 inhibitors, or sulfonylureas;
- Use of fibrates, omega 3 (fish oil), niacin, or PCSK9 antagonists;
- Use of systemic glucocorticoids within 60d prior to participation;
- Hematocrit <35%;
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 |
|---|---|---|
| Standardized DinnerDe novo lipogenesis (DNL) will be assessed in all participants with a standardized dinner | Behavioural | IR participants with standardized dinner, IR participants with standardized dinner and premeal exercise |
| Premeal exerciseDNL will be assessed in all participants with short bouts of premeal exercise with a standardized dinner | Behavioural | IR participants with standardized dinner and premeal exercise |
Primary outcome
Effect of tissue-specific insulin resistance on contribution of DNL to plasma triglyceride
Time frame: Baseline
The amount of de novo lipogenesis (DNL) in VLDL-triglycerides after a standard meal will be measured in plasma from whole blood. Relationship between DNL and 1) whole body (skeletal muscle) insulin resistance and 2) white adipose tissue insulin resistance will be assessed individually.
Change in DNL in VLDL-triglycerides after a standard meal compared to a standard meal with premeal exercise.
Time frame: study visit 1 and study visit 2, up to 8 weeks
The amount of de novo lipogenesis (DNL) in VLDL-triglycerides after a standard meal vs after a standard meal with premeal exercise will be measured in plasma from whole blood.
4 secondary outcomes
Change in plasma triglycerides after a standard meal compared to a standard meal with premeal exercise
Time frame: study visit 1 and study visit 2, up to 8 weeks
Baseline plasma triglycerides
Time frame: baseline
Adipose insulin sensitivity
Time frame: Baseline
Skeletal muscle/whole-body insulin sensitivity assessed by oral glucose tolerance test (OGTT)
Time frame: Baseline
Results and safety
The study was stopped early (reason given: Poor accrual and lack of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: Yes. By reasonable request, PI can be reached by email, and individual participant data (OGTT results, fasting plasma data, DNL data) will be provided electronically.
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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. This study is not recruiting at the moment.
Daniel F Vatner, MD, PhD principal investigator
Yale 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 Standardized Dinner and Premeal exercise in people with Insulin Resistance and Hypertriglyceridemia, run by Yale 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 5 inclusion and 7 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: stopped early, as of the sponsor's last update on 27 Oct 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?
The study was stopped early (reason given: Poor accrual and lack of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of tissue-specific insulin resistance on contribution of DNL to plasma triglyceride (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2026.