Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes
3 other identifiers
interventional
40
1 country
1
Brief 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 these groups.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Nov 2023
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 15, 2023
CompletedFirst Posted
Study publicly available on registry
February 24, 2023
CompletedStudy Start
First participant enrolled
November 16, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
January 27, 2026
January 1, 2026
2.5 years
February 15, 2023
January 23, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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.
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
study visit 1 and study visit 2, up to 8 weeks
Baseline plasma triglycerides
baseline
Adipose insulin sensitivity
Baseline
Skeletal muscle/whole-body insulin sensitivity assessed by oral glucose tolerance test (OGTT)
Baseline
Study Arms (2)
IR participants with standardized dinner
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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.
Interventions
De novo lipogenesis (DNL) will be assessed in all participants with a standardized dinner
DNL will be assessed in all participants with short bouts of premeal exercise with a standardized dinner
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Yale Universitylead
- Amsterdam UMCcollaborator
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)collaborator
Study Sites (1)
AMC Amsterdam
Amsterdam, Netherlands
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel F Vatner, MD, PhD
Yale University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 15, 2023
First Posted
February 24, 2023
Study Start
November 16, 2023
Primary Completion (Estimated)
June 1, 2026
Study Completion (Estimated)
June 1, 2026
Last Updated
January 27, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- Data will be available when data collection ends until 36 months after publication.
By reasonable request, PI can be reached by email, and individual participant data (OGTT results, fasting plasma data, DNL data) will be provided electronically.