NCT05743868

Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
BEHAVIORAL	Standardized Dinner	De novo lipogenesis (DNL) will be assessed in all participants with a standardized dinner
BEHAVIORAL	Premeal exercise	DNL will be assessed in all participants with short bouts of premeal exercise with a standardized dinner

Timeline

• Start date: 2023-11-16
• Primary completion: 2026-06-01
• Completion: 2026-06-01
• First posted: 2023-02-24
• Last updated: 2026-01-27

Locations

1 site across 1 country: Netherlands