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Recruiting NCT05743868

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

No phase Interventional Insulin Resistance Hypertriglyceridemia

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Standardized Dinner, Premeal exercise.
Who it may be relevant to
Registry conditions: Insulin Resistance, Hypertriglyceridemia. Basic parameters: 18 years — 65 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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.

Interventions

  • 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

Primary outcome measures

  • Effect of tissue-specific insulin resistance on contribution of DNL to plasma triglyceride [Time frame: Baseline]
  • 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]
Secondary outcome measures (4)
  • 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]

Eligibility criteria

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 criteria

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Crossover
Masking
Open label
Primary purpose
Basic science

Study locations

Netherlands · 1 center
  • AMC Amsterdam — Amsterdam

Identifiers

NCT: NCT05743868 · Vatner 012523 · NL83166.018.22 · R01DK124272

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗