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NCT00277342 Clinical Trial

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

Polymorphism Liver FABP Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT00277342
Other study ID # MOW_MM_LFABP
Secondary ID
Status Completed
Phase N/A
First received January 12, 2006
Last updated May 3, 2012
Start date January 2006
Est. completion date April 2006

Study information
Verified date August 2006
Source German Institute of Human Nutrition
Contact n/a
Is FDA regulated No
Health authority Germany: Ethics Commission
Study type Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility
Status Completed
Enrollment 18
Est. completion date April 2006
Est. primary completion date
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 70 Years
Eligibility 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

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

Intervention

Procedure:
• measurement of lipid-induced hepatic insulin resistance

Locations
Country Name City State
Germany German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke Nuthetal

Sponsors (1)
Lead Sponsor Collaborator
German Institute of Human Nutrition

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Weickert MO, Loeffelholz CV, Roden M, Chandramouli V, Brehm A, Nowotny P, Osterhoff MA, Isken F, Spranger J, Landau BR, Pfeiffer AF, Möhlig M. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary lipid-induced hepatic insulin resistance(WT vs.SNP L-FABP)
Primary changes in the relation GNG to GL
Secondary changes in peripheral plasma glucose and lipid responses

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