Medical Student Research Fellowship for Summer 2007

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: 214 648 2869
E-mail: Gloria.Vega@utsouthwestern.edu
Project title: Obesity and metabolic Risk Factors in the Dallas Heart Study

Human subjects IRB approved project number (where applicable): Study completed. Need to do data analyses

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): The DHS study I was a multi-ethnic study designed to evaluate the prevalence of CHD risk factors in the Dallas Fort Worth population.

Brief Description of Project:
The summer projects involve assessment of body fat distribution and metabolic risk factors in the DHS I study.

Previous Research Activities or Publications with Medical Students:
J Clin Endocrinol Metab. 2006 Nov;91(11):4459-66. Epub 2006 Aug 22.

Influence of body fat content and distribution on variation in metabolic risk.

Vega GL, Adams-Huet B, Peshock R, Willett D, Shah B, Grundy SM.

Donald W.Reynolds Cardiovascular Clinical Research Center and Department of
Internal Medicine, Center for Human Nutrition, University of Texas Southwestern
Medical Center, Dallas, Texas 75390-9052, USA.

OBJECTIVES: Several reports indicate that the body fat compartments, especially
ip fat, predict metabolic risk better than total body fat. The objective of the
study was to determine whether this can be confirmed and generalized throughout
the population. PARTICIPANTS: A representative sample of 1934 Black and White
women and men of the Dallas Heart Study participated in the study. DESIGN: We
measured the fat in total body, trunk, and lower body with dual-energy x-ray
absorptiometry and in abdominal compartments (sc, ip, and retroperitoneal) with
magnetic resonance imaging. Other measurements included body mass index (BMI),
waist circumference, blood pressure, plasma lipids, glucose, insulin (including
homeostasis model), and C-reactive protein. RESULTS: In all groups, total body
fat correlated positively with key metabolic risk factors, i.e. homeostasis
model, triglyceride/high-density lipoprotein-cholesterol ratios, C-reactive
protein, and blood pressure; however, it explained less than one third of the
variability of all the risk factors. After adjustment for total body fat,
truncal fat conferred additional positive correlation with risk factors.
Furthermore, with multivariable regression analysis, ip fat conferred
independent correlation with plasma lipids beyond a combination of other
compartments including truncal fat. Still, except for insulin levels, all
combinations including ip fat still explained less than one third of the
variability in risk-factor levels. Conversely, lower body fat correlated
negatively with risk factors; i.e. lower body fat appeared to offer some
protection against risk factors. CONCLUSIONS: Body fat distribution has some
influence on risk factors beyond total body fat content. Both waist
circumference and BMI significantly predicted risk factors after adjustment for
total body fat, and for clinical purposes, most of the predictive power for men
was contained in waist circumference, whereas for women, BMI and waist
circumference were similarly predictive. Finally, even though the correlations
between combined body fat parameters and risk factors explained only a portion
of the variation in the latter, the average number of categorical metabolic risk
factors increased progressively with increasing obesity. Hence, obesity
seemingly has more clinical impact than revealed in these correlative studies.

Metabolic Syndrome and Related Disorders (in press)
Endothelial Lipase Abnormalities in Very Obese Women with the Metabolic Syndrome
Craig Chang, M.D.1* Ana-Barbara Garcia-Garcia, Ph.D.4* Elizabeth Hamilton, M.D.1*
Brijen Shah, M S II4* Shinichi Meguro, M.S. Pharm.4 Scott M. Grundy, M.D., Ph.D.2, 3, 4, 5
David Provost, M.D.1 Gloria Lena Vega, Ph.D.2, 3, 4,5
Abstract

Objective: This study was carried out to determine whether very obese women have abnormalities in plasma levels, particle sizes, and post-heparin lipase activities.
Research Methods and Procedures: Three groups were studied: 28 non-obese women, 17 very obese women without diabetes, and 11 very obese women with diabetes. Most subjects in the very obese groups had metabolic syndrome. Subjects had plasma lipoproteins and lipase activities measured.
Results: As shown below, very obese women had elevated HOMA-IR and C-reactive protein. They also had higher triglycerides and lower HDL cholesterol levels than non-obese subjects. Very obese women had significant reductions in lipoprotein lipase (LPL) activities. Also, they had higher hepatic triglyceride lipase (HTGL) compared to non-obese. The ratios of LPL/HTGL were markedly reduced. In spite of severe obesity and reduced LPL, serum triglycerides were marginally elevated in the obese group compared to non-obese subjects.

a Significantly different from Non-Obese; P < 0.05; b Significantly different from Non-DM; P < 0.05
Conclusion: Higher HTGL in the obese subjects may have contributed to lower HDL-cholesterol while abnormal ratios of LPL/HTGL may have contributed to the prevalence of small particles in the obese subjects.

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