Trial Information

USC Center for Transdisciplinary Research on Energetics and Cancer or Obesity-Related Metabolic Disease Risk: Response to Exercise in Minority Youth

A.1 Aims

The overall goal of this project is to examine role of strength training as a therapeutic
intervention to improve the cancer and obesity-related metabolic risk profile in
African-American adolescents. The project is prompted by the urgent public health need to
prevent and treat cancer and obesity-related problems, including diabetes and cardiovascular
disease, in African-American adolescents, a population that is understudied and medically
under-served in the Los Angeles area. A recent report from the Institute of Medicine
underscored this major public health concern in the childhood obesity field:

"Children's health has made tremendous strides over the past century. In general, life
expectancy has increased by more than thirty years since 1900 and much of this improvement
is due to the reduction of infant and early childhood mortality. Given this trajectory
toward a healthier childhood, the investigators begin the 21st century with a shocking
development - an epidemic of obesity in children and youth. The increased number of obese
children throughout the US during the past 25 years has led policymakers to rank it as one
of the most critical public health threats of the 21st century. (92)" Obesity and metabolic
syndrome problems disproportionately affect African-American adolescents (51). This project
will explore why African-Americans have greater cancer risk than Hispanics (91), despite a
reduced prevalence of the metabolic syndrome (7, 62).

Preliminary work from this laboratory has shown that both African-American and Hispanic
children are more insulin resistant than Caucasian children, and this difference is
apparently not explained by differences in body fatness. Moreover, the metabolic
compensation to a similar degree of insulin resistance markedly differs between
African-American and Hispanic children (62). African-Americans display greater
hyperinsulinemia in response to a glucose challenge, whereas Hispanics have a more subdued
increase in insulin levels due to an increase in second phase insulin secretion. The
investigators will have the opportunity to build upon this preliminary work to examine the
effects of resistance training on three factors predictive of cancer and metabolic disease
risk: 1) body fat distribution; 2) insulin resistance and 3) measures of oxidative stress in
African America adolescents. The investigators previously studying Hispanic adolescents in a
parallel protocol.

The overall hypotheses of this project are that: (1) hyperinsulinemia in overweight
African-American youth is associated with increased long-term cancer risk; and (2) insulin
resistance, obesity and oxidative stress in overweight African-American youth will be
improved with chronic resistance training and a modified carbohydrate dietary approach. The
investigators will specifically examine the following metabolic outcomes, because they have
been hypothesized to contribute to the obesity-related increase in cancer and metabolic
disease risk:

- Insulin concentrations and insulin sensitivity;

- Total body fat, abdominal visceral fat, muscle fat and liver fat;

- Circulating adipocytokines;

- Intima-media thickness of the carotid artery

- Markers of oxidative stress, including: F2-isoprostanes, malondialdehyde (MDA),
myeloperoxidase (MPO), oxygen radical absorbance capacity and ROS detection by flow
cytometry.

A.2 Aims

The specific aims and hypotheses of project 1 are as follows:

Study 1: Cross-Sectional Measures Specific Aim 1 (Body Fat Compartments): To determine the
association of visceral fat, muscle and liver fat and plasma adipocytokines to variation in
insulin resistance in African-American youth.

- Hypothesis 1: Visceral fat, muscle and liver fat, and adipokines will independently
contribute to greater insulin resistance.

• Specific Aim 2 (Insulin Resistance): To examine metabolic compensation to insulin
resistance in African-American youth.

- Hypothesis 2: Insulin resistant African-American youth will exhibit a higher acute
insulin response to glucose.

• Specific Aim 3 (Oxidative Stress): To examine the influence of body fat and insulin
resistance on markers of oxidative stress and markers of metabolic disease risk.

- Hypothesis 3: Increased total body fat and insulin resistance will be associated with
greater oxidative stress. The increased oxidative stress will be correlated with the
higher acute insulin response.

Study 2 (Randomized Trial of Modification of Carbohydrate Intake and Strength Training) •
Specific Aim 4 (Linkage of factors in Aims 1-3): To determine the effects of a randomized
modification of carbohydrate intake, and/or strength training intervention in overweight
African-American adolescents on potential factors linking obesity, insulin resistance, and
oxidative stress.

- Hypothesis 4: Strength training will improve metabolic factors for cancer risk. That is,
resistance training will reduce visceral fat; increase insulin sensitivity, reduce
hyperinsulinemia, and reduce oxidative stress. The decreases in total body fat and visceral
adipose tissue will be associated with improved insulin sensitivity and oxidative stress.