Postprandial VLDL-triglyceride Metabolism in Type 2 Diabetes Patients With and Without NAFLD

March 20, 2024 updated by: University of Aarhus

Postprandial Hepatic Fatty Acid Metabolism During Oral High-fat Mixed-meal Challenge Test in Patients With Type 2 Diabetes With and Without NAFLD

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH). The mechanisms behind why some subjects progress from NAFLD to NASH are not clear and the responsible mechanism for storage of excess amounts of liver fat in patients with NAFLD are poorly understood.

Patients with type 2 diabetes mellitus (T2D) and abdominally obese subjects very often have accumulation of liver fat (NAFLD).

T2D is also associated with abnormal lipid metabolism (dyslipidemia), including free fatty acids (FFA), hypertriglyceridemia and excessive postprandial hyperlipidemia which increases the risk of ischemic cardiovascular disease (CVD) and heart failure.

In healthy, insulin sensitive subjects the postprandial increase in triglycerides (TG) is primarily caused by meal derived chylomicrons, whereas endogenously produced TG (VLDL-TG) and decreased peripheral TG clearance only becomes quantitatively important in insulin resistant subjects .Thus, postprandial lipidemia in T2D results from both chylomicronemia as well as a reduction in both insulin mediated suppression of VLDL-TG secretion and lipoprotein lipase (LPL) mediated peripheral clearance. A recent study demonstrated that the ability of insulin to suppress hepatic VLDL-TG after a fat-enriched meal and the duration of the postprandial hyperlipidemia was similar in patients with T2D compared with age- and BMI matched individuals without T2D, indicating that the degree of insulin mediated VLDL-TG secretion and hyperlipidemia primarily depends on insulin sensitivity and not the presence of T2D diabetes per se.

In these studies, the investigators want to examine the effect of a fat enriched mixed-meal on hepatic VLDL-TG handling and adipose storage capacity in patients with T2D with and without NAFLD. Investigators will address these questions using carboxyl-14C triolein labeled VLDL-TG, magnetic resonance (MR) spectroscopy of liver, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression.

The overarching goals are to define abnormalities and differences between patients with T2D with and without NAFLD in terms of hepatic lipid metabolism.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Denmark
      • Aarhus N, Denmark, 8200
        • Department of Endocrinology and Internal Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects with Type 2 Diabetes with and without NAFLD (steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups)

Exclusion Criteria:

  • Active smoking
  • Comorbidity other than hypertension and hyperlipidemia
  • Fixed medical drug consumption (including insulin) except statins and anti-diabetic medications. However, statins must be paused 2 weeks before the examination date and other antidiabetic medication on examination date.
  • Patients with cancer or former cancer patients
  • Blood donation within the last 3 months prior to the study
  • Participation in experiments involving radioactive isotopes within the last 3 months
  • Alcohol abuse (over 21 items per week for men and over 14 for women)
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Type 2 Diabetes with NAFLD

Patients with Type 2 Diabetes with NAFLD

MR spectroscopy verified steatosis
Dietary supplement: High-fat mixed-meal tolerance test (HF-MMTT)
The test meal consists of a standardized HF-MMTT (791 cal) with 197 g cream (38 % fat), 18 g sugar and 1 g vanilla sugar for taste (75 g fat, 25 g carbohydrate and 4 g protein)
Active Comparator: Type 2 Diabetes without NAFLD

Patients with Type 2 Diabetes without NAFLD

MR spectroscopy verified no steatosis
Dietary supplement: High-fat mixed-meal tolerance test (HF-MMTT)
The test meal consists of a standardized HF-MMTT (791 cal) with 197 g cream (38 % fat), 18 g sugar and 1 g vanilla sugar for taste (75 g fat, 25 g carbohydrate and 4 g protein)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
VLDL-triglyceride secretion - Ex vivo labeled VLDL - [14C]-triolein tracer technique.
Time Frame: 1 day
(μmol/min)
1 day
VLDL-triglyceride uptake in muscle - Measurement of fatty acid concentration and specific activity in muscle biopsies
Time Frame: 1 day
(percent)
1 day
VLDL-triglyceride uptake in adipose tissue - Measurement of fatty acid concentration and specific activity in adipose tissue biopsies
Time Frame: 1 day
(percent)
1 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
VLDL-triglyceride oxidation - Oxidation is measured by specific activity in exhaled air.
Time Frame: 1 day
(μmol/min)
1 day
Adipose cell size measurement
Time Frame: 1 day
(μl)
1 day
Insulin sensitivity
Time Frame: 1 day
(mg/kg/min)
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Danish Diabetes Academy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 14, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 23, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 4, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 14, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 21, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 01072021

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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