News & Research

    University of Pittsburgh , Pittsburgh, Pennsylvania

Decreased fat oxidation - metabolic inflexibility in African-American women

General Research Subject: Insulin Resistance Pre Diabetes

Focus: Clinical Therapeutics/New Technology\Glucose Monitoring and Sensing, Insulin Action\Insulin Resistance, Integrated Physiology\Fatty Acid Metabolism, Integrated Physiology\Muscle

Type of Grant: Clinical Translational Research

Project Start Date: January 1, 2011

Project End Date: December 31, 2013

Research Description

While it is well known that obesity is a major public health challenge, the disproportionate rise in obesity among African-Americans (AA), particularly women, is less well recognized. Obesity-associated diseases, including diabetes are also found at higher rates in AA women. The reasons for this racial disparity in obesity and associated diseases are not entirely clear, but emerging data suggests that AA women appear to be unable to appropriately switch between the use of carbohydrate and fat. This decreased fat oxidation could lead to increased obesity and to greater insulin resistance that has also been observed in AA women. The hypothesis being examined in this proposal is that decreased skeletal muscle fat oxidation leads to increased storage of fat in adipose tissue and in skeletal muscle, and is a link between the development of obesity, insulin resistance and Type 2 diabetes in AA women. The investigators will examine fat oxidation during an exercise test, liver and muscle insulin sensitivity, and skeletal muscle characteristics in AA and Caucasian women to confirm the limited evidence of racial differences in fat oxidation and insulin sensitivity and the relation between the two. Furthermore, they will examine muscle characteristics that may play a role in these racial differences. Investigating the role of decreased fat oxidation and muscle characteristics that may explain the decreased insulin sensitivity in AA women is critical to the understanding of the underlying physiology related to the increased obesity and obesity-related chronic diseases in this population.

Research Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

This project addresses potential reasons for the increased diabetes that is observed in African-American women. The project addresses the decreased ability to burn fat observed in African-American women, and whether differences in skeletal muscle play a role in the lower insulin sensitivity that is also observed in African-American women. The results from this project may indicate that increasing physical activity may be particularly important in African-American women.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The increased diabetes observed in African-American women may be due to genetic differences in their skeletal muscle which result in a decreased ability to burn fat, resulting in increased storage of fat in muscle which leads to insulin resistance, which is a risk for diabetes. These findings may indicate that increased physical activity, which has been shown to increase the ability of the body to burn fat and increase insulin sensitivity, may be critical for preventing diabetes in African-American women.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts?

It is personally important for me to become involved in diabetes research because my wife is insulin resistant requiring oral agents. Her grandmother had diabetes requiring insulin injections, so she may have a genetic predisposition for development of diabetes. Furthermore, my mother is insulin resistant requiring oral agents, and I have elevated fasting glucose, so I may also a genetic predisposition for development of diabetes.

I began my career focusing primarily on obesity research, but have been involved in diabetes research as well, since the risk of developing diabetes is greatly increased in obese individuals. During my years of obesity research, I became aware of the increased incidence of obesity and diabetes in African-Americans, but particularly in African-American women.

My involvement in diabetes research increased dramatically when I was recruited by Dr. David Kelley to join the faculty at the University of Pittsburgh. While working on projects with my colleagues, I observed that fat oxidation was lower in African-American women, and that this phenomenon has been observed in several studies. I was also aware that insulin resistance is higher in African-American women even though they have lower fat deposited in the belly, which is normally associated with less insulin resistance. Furthermore, we observed a lower liver fat, which is even more strongly associated with insulin resistance than belly fat, in African-American women in our recent study in severely obese. Therefore, the insulin resistance in African-American women appears to be different from that observed in Caucasian women, and suggests that skeletal muscle differences may be involved. This research award will allow me to try to understand these findings, to begin to better understand the insulin resistance in African-American women.

In what direction do you see the future of diabetes research going?

I see diabetes research moving more at the cellular and sub cellular level, understanding genetic predisposition for diabetes, and effective methods of improving insulin sensitivity, preventing the progression to future diabetes.