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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by German Diabetes Center
Sponsor:
Collaborator:
German Centers for Diabetes Research (DZD)
Information provided by (Responsible Party):
Bettina Nowotny, German Diabetes Center
ClinicalTrials.gov Identifier:
NCT01736202
First received: November 26, 2012
Last updated: NA
Last verified: November 2012
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Insulin Sensitivity
Biological: fat orally
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity (FLAME-study)

Resource links provided by NLM:


Further study details as provided by German Diabetes Center:

Primary Outcome Measures:
  • Effect of intervention on whole body insulin sensitivity [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of intervention on hepatic insulin sensitivity [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Effect of intervention on rates of gluconeogenesis and glycogenolysis [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: March 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Palm oil orally
oral fat load
Biological: fat orally
Oral ingestion of palm oil or canola oil at timepoint zero
Active Comparator: Canola oil orally
Oral fat load
Biological: fat orally
Oral ingestion of palm oil or canola oil at timepoint zero
Placebo Comparator: Water orally
oral water administration as control

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.

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736202

Locations
Germany
German Diabetes Center Recruiting
Düsseldorf, Nordrhein-Westfalen, Germany, 40225
Contact: Sabine Kahl, M.D.    +492113382740    sabine.kahl@ddz.uni-duesseldorf.de   
Contact: Bettina Nowotny, M.D.    +492113382575    bettina.nowotny@ddz.uni-duesseldorf.de   
Principal Investigator: Sabine Kahl, M.D.         
Sponsors and Collaborators
German Diabetes Center
German Centers for Diabetes Research (DZD)
Investigators
Study Director: Michael Roden, Prof., M.D. German Diabetes Center
  More Information

No publications provided

Responsible Party: Bettina Nowotny, Leader Clinical Research Center, German Diabetes Center
ClinicalTrials.gov Identifier: NCT01736202     History of Changes
Other Study ID Numbers: FLAME
Study First Received: November 26, 2012
Last Updated: November 26, 2012
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Diabetes Center:
oral fat
insulin sensitivity

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014