Request for Funding

Medical Student Research Fellowship for Summer 2002

Mentor: Scott M. Grundy, M.D., Ph.D. and Gloria Lena Vega, Ph.D.
Department: Center for Human Nutrition
Room number: Y3.206
Mail Code: 9052
Phone number: 8 2869
E-mail: Gloria.Vega
Project title: Etiology of Non-alcoholic Fatty Liver

Human subjects IRB approved project number (where applicable): 1201-621

Project Type : Patient-based research

Brief Description of Project:

Abstract: The purpose of the study is to determine the etiology of non-alcoholic fatty liver. Two mechanisms may pertain: (1) accumulation of triglyceride in the liver as a result of insulin resistance or (2) defective oxidation of fatty acids.

The proposed study is an outgrowth of the grant from The Donald W. Reynolds Foundation to the University of Texas Southwestern. One of the major components of the Reynolds Center is The Dallas Heart Disease Prevention Project (DHDPP). A random, multiethnic population database is being developed by testing of 7000 individuals aged 18-65 from Dallas County. Subjects are characterized with respect to medical history, family history, blood pressure, fasting lipoproteins and other plasma constituents, EKG, MRI to assess cardiac mass and geometry, MRI to assess regional body fat, electron beam CT (EBCT) to assess coronary calcification, DEXA scanning to determine body fat content and fat distribution, and nuclear magnetic resonance (NMR) of the liver to determine liver fat content. DNA is banked from each subject for genotyping.

The current proposal is an outgrowth of the measurement of liver fat by NMR in the Reynolds population. In this study, subjects were identified as having a fatty liver (> 10% fat in the liver by nuclear magnetic resonance (NMR)) and another group serving as a reference group had < 5% fat in the liver. Sixty adult men and women with a fatty liver and 60 controls will be selected for study. Subjects may have participated in the DHDPP protocol or they may be new candidates recruited independently of the DHDPP. The study will be carried out in the General Clinical Research Center (GCRC). Subjects will have baseline tests that include clinical history and complete physical examination, vital signs, and anthropometry, chemistries to assess liver and renal function, CK, CBC and urine analysis, plasma lipids and lipoprotein cholesterol measured after a 12 hour fast, measurement of IR with an extended oral glucose tolerance test, and in selected persons, measurements of plasma ketone bodies after a 48-hour fast. Subjects selected for the 48-hour fast will be those who have fatty liver in the absence of evidence for IR. Polymorphisms for candidates genes for insulin resistance and fatty acid oxidation defects will be measured in all or selected subjects. All subjects will be screened for known polymorphisms in candidate genes for IR. In addition, patients who are found to have low levels of plasma ketone bodies after prolonged fast will be screened for known polymorphisms for candidate genes for fatty acid oxidation defects. Subject participation in the study will last at most 2 days. Subjects who had a DEXA and MRI for liver fat 3 months before recruitment will likely have these tests repeated during this trial. Also, subjects who had marked changes in body weight since their participation in the DHDPP study will also have DEXA and liver MRI repeated. All other subjects with recent testing in the DHDPP (< 3 months) will not need DEXA or MRI.

Previous Research Activities or Publications with Medical Students:

Doris Duke Fellows: 2001 - 2002

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