Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity (FLAME)

August 23, 2023 updated by: German Diabetes Center

Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity (FLAME-study)

The development of type 2 diabetes is based on a combination of insulin resistance and beta cell dysfunction. In the last years, elevated FFA were recognized as a key players in the pathogenesis of insulin resistance and type 2 diabetes.

The study compares the acute effects of an oral lipid bolus on insulin sensitivity and hepatic glucose metabolism in healthy humans.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) represents one key mechanism in the pathogenesis of insulin resistance, which contributes to the development of type 2 diabetes (T2D). In most cases, dyslipidemia is related to obesity and the metabolic syndrome. Not only skeletal muscle glucose uptake, but also hepatic glucose fluxes are altered in insulin resistant states. In obese and T2D subjects, rates of gluconeogenesis (GNG) are increased, but in obese normoglycemic subjects endogenous glucose production (EGP) remains constant because of downregulation of glycogenolysis (GL). However, in T2D subjects, both GNG and GL are elevated, contributing to fasting and postprandial hyperglycemia. Therefore, elevated GNG rates may represent an early event in the pathophysiology of insulin resistance and T2D.

Preliminary studies of our institute show that intravenous lipid infusion with subsequent elevation of FFA results in increased GNG rates without alteration of EGP in lean, non-diabetic subjects. In another recent study we investigated the effects of an oral fat load on hepatic insulin sensitivity. As expected, we did not find any alterations in EGP; however, rates of GNG and GL have not been assessed.

The aim of this study is to analyze the effects of an oral fat load with transiently elevated levels of circulating lipids on hepatic glucose fluxes, especially GNG and GL, to elucidate the role of dietary fat in the induction of insulin resistance in healthy humans.

In this randomized, controlled cross-over study, effects of oral palm oil and canola oil ingestion will be investigated in young, healthy lean subjects. Hepatic glucose fluxes will be assessed by two independent methods, in vivo magnet resonance spectroscopy (MRS) and the deuterated water/acetaminophen method, which also allows for the determination of glycogen cycling rates. Furthermore, hepatic phosphorus metabolites and liver fat content will be monitored by MRS.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

  • Germany
    • Nordrhein-Westfalen
      • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
        • German Diabetes Center

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

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • healthy male and female subjects
  • age 20-40
  • BMI 20-25 kg/m2

Exclusion Criteria:

  • hyperlipidemia
  • smoking
  • pregnancy
  • allergy against paracetamol/palm oil/canola oil
  • contraindication for MRI investigations
  • anaemia
  • taking drugs influencing lipid or glucose metabolism, the immune system or antihypertensive treatment
  • M. Meulengracht
  • Hepatitis/HIV
  • chronic diseases

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: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Palm oil orally
oral fat load
Biological: fat orally
Oral ingestion of palm oil or canola oil or water at timepoint zero
Other Names:
  • water orally
Active Comparator: Canola oil orally
Oral fat load
Biological: fat orally
Oral ingestion of palm oil or canola oil or water at timepoint zero
Other Names:
  • water orally
Placebo Comparator: Water orally
oral water administration as control
Biological: fat orally
Oral ingestion of palm oil or canola oil or water at timepoint zero
Other Names:
  • water orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in rate of glucose disappearance (Rd)
Time Frame: 6 hours
Measurement of whole body insulin sensitivity in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics
6 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in rate of hepatic endogenous glucose production (EGP)
Time Frame: 6 hours
Measurement of hepatic EGP in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics
6 hours

Collaborators and Investigators

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

Sponsor

German Diabetes Center

Collaborators

German Center for Diabetes Research

Investigators

  • Study Director: Michael Roden, Prof., MD, German Diabetes Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

March 1, 2012

Primary Completion (Actual)

January 1, 2022

Study Completion (Actual)

January 1, 2022

Study Registration Dates

First Submitted

November 26, 2012

First Submitted That Met QC Criteria

November 26, 2012

First Posted (Estimated)

November 29, 2012

Study Record Updates

Last Update Posted (Actual)

August 25, 2023

Last Update Submitted That Met QC Criteria

August 23, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FLAME

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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