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

Last updated: March 7, 2025
Sponsor: Yale University
Overall Status: Active - Recruiting

Phase

N/A

Condition

Stress

Hypertriglyceridemia

Diabetes Prevention

Treatment

Premeal exercise

Standardized Dinner

Clinical Study ID

NCT05743868
Vatner 012523
NL83166.018.22
R01DK124272
  • Ages 18-65
  • All Genders

Study 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 Criteria

Inclusion

Inclusion Criteria:

  • 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

Exclusion

Exclusion Criteria:

  • Active or chronic liver disease, kidney disease, congestive heart failure, unstableangina, history of acute cardiovascular events within 6mo of screening, history ofseizures 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.

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: Premeal exercise
Phase:
Study Start date:
November 16, 2023
Estimated Completion Date:
December 31, 2025

Study 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.

Connect with a study center

  • AMC Amsterdam

    Amsterdam,
    Netherlands

    Active - Recruiting

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