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Potential Association of a Common L-FABP Polymorphism With Lipid-induced Hepatic Insulin Resistance

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ClinicalTrials.gov Identifier: NCT00277342
Recruitment Status : Completed
First Posted : January 16, 2006
Last Update Posted : May 4, 2012
Sponsor:
Information provided by:
German Institute of Human Nutrition

Brief Summary:
The investigators hypothesise that a common A277G polymorphism of the liver fatty acid binding protein (L-FABP) gene, which leads to an amino acid exchange, may be associated with alterations of lipid-induced hepatic insulin resistance. In the present study the investigators will investigate potential differences in lipid-induced hepatic insulin resistance, and in the relation between glycogenolysis and gluconeogenesis, in healthy subjects with the A277G polymorphism vs. subjects carrying the wildtype.

Condition or disease Intervention/treatment Phase
Wildtype Polymorphism Liver FABP Procedure: measurement of lipid-induced hepatic insulin resistance Not Applicable

Detailed Description:
Liver fatty acid binding protein (L-FABP) is an abundant cytosolic lipid-binding protein that regulates lipid transport and metabolism. Only one common non-synonymous polymorphism (A227G) leading to an amino-acid exchange in the exonic region of the L-FABP gene has been previously identified. Experimental elevations of free fatty acids (FFAs) have been shown to impair insulin mediated suppression of endogenous glucose production (EGP). Deletion of the L-FABP gene shows no obvious phenotype in mice receiving a low fat chow diet, but leads to decreased hepatic triglyceride accumulation in the prolonged fasted state, which exposes mice to an increased fatty acid flux to the liver. The function of the L-FABP gene may be altered by polymorphisms in coding regions of the gene, probably leading to modifications in hepatic triglyceride accumulation and hepatic insulin resistance.We hypothesize that carriers of the A277G SNP, when compared to matched wild-type subjects, may show altered responses of hepatic glucose production upon exposure to increased peripheral fatty acid concentrations, as achieved by lipid / heparin infusions. Because it is known that free fatty acids potently increase insulin secretion, we use somatostatin clamps in our experiments, followed by replacement of postabsorptive insulin and glucagon concentrations.

Study Type : Interventional  (Clinical Trial)
Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
Primary Purpose: Diagnostic
Study Start Date : January 2006
Study Completion Date : April 2006

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Primary Outcome Measures :
  1. lipid-induced hepatic insulin resistance(WT vs.SNP L-FABP)
  2. changes in the relation GNG to GL

Secondary Outcome Measures :
  1. changes in peripheral plasma glucose and lipid responses


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy subjects with normal glucose tolerance (NGT)

Exclusion Criteria:

  • any severe cardiac, liver, or kidney diseases
  • pregnant or lactating women, menstrual irregularities
  • cortisone, antidiabetic drugs

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00277342


Locations
Germany
German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke
Nuthetal, Germany, 14558
Sponsors and Collaborators
German Institute of Human Nutrition
Investigators
Principal Investigator: Martin O Weickert, MD German Institute of Human Nutrition; Charité Campus Benjamin Franklin
Principal Investigator: Matthias Möhlig, MD German Institute of Human Nutrition; Charité Campus Benjamin Franklin
Study Chair: Andreas FH Pfeiffer, MD German Institute of Human Nutrition; Charité Campus Benjamin Franklin

Additional Information:
Publications of Results:
ClinicalTrials.gov Identifier: NCT00277342     History of Changes
Other Study ID Numbers: MOW_MM_LFABP
First Posted: January 16, 2006    Key Record Dates
Last Update Posted: May 4, 2012
Last Verified: August 2006

Keywords provided by German Institute of Human Nutrition:
lipid induced hepatic insulin resistance
polymorphisms liver fatty-acid-binding-protein
gluconeogenesis
glycogenolysis
endogenous glucose production

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs