Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes
Status: Recruiting
Location: See location...
Intervention Type: Behavioral
Study Type: Interventional
Study Phase: Not Applicable
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.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 65
Healthy Volunteers: f
View:
• 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
Locations
Other Locations
Netherlands
AMC Amsterdam
RECRUITING
Amsterdam
Contact Information
Primary
Daniel F Vatner, MD, PhD
daniel.vatner@yale.edu
203 785 5934
Time Frame
Start Date: 2023-11-16
Estimated Completion Date: 2026-06
Participants
Target number of participants: 40
Treatments
Experimental: IR participants with standardized dinner
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.
Experimental: IR participants with standardized dinner and premeal exercise
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.
Related Therapeutic Areas
Sponsors
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Amsterdam UMC
Leads: Yale University