Istfan, Nawfal W., PhD
Carbohydrate Overfeeding as a Cause of Oxidative Stress
General Research Subject: Obesity
Focus: Adipocytes, Insulin Action\Metabolism, Integrated Physiology, Integrated Physiology\Fatty Acid Metabolism
Type of Grant: Innovation
Project Start Date: January 1, 2013
Project End Date: December 31, 2014
Overfeeding leads to obesity and worsens the severity of diabetes. Despite increasing public awareness of the importance of these diseases, we do not understand how overeating contributes to disease progression. We are proposing a new mechanism that relates overeating to some of the changes that are known to exist in fat cells and that explain the association between obesity and disease. In this project, we will establish a new model to study this mechanism in human subjects under experimentally controlled conditions.
We will use a common method whereby insulin and glucose are given at specific rates to simulate overeating of carbohydrates. We will show that when new fat is being made from sugar, the body responds in a way similar to what happens in response to an injury. This is called inflammation and is now a recognized cause of disease in obesity and diabetes. We will measure changes in fat cells at the same time that new fat is being made. This will help us to understand how overeating of carbohydrates adversely affects fat cells and the development of obesity and diabetes. We expect that this project will help design new studies in an area of human research that has been previously ignored. Better understanding of how obesity and diabetes develop will lead to improved treatments for these common diseases.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and curing diabetes?
Our project, Carbohydrate Overfeeding as a Cause of Oxidative Stress, falls within the effort to understand the relationships between obesity, type 2 diabetes and the development of inflammation and cardiovascular disease. Although these relationships are well characterized, the question of how they arise remains largely unanswered. Our project focuses on the role of overfeeding in triggering the cellular mechanisms that ultimately lead to inflammation, insulin resistance and development of clinical type 2 diabetes.
This project will help understand the pathophysiological mechanisms that underlie overfeeding in the development of obesity and diabetes. This understanding will ultimately help focus medical attention on prevention of positive energy balance and weight gain as key in the fight against obesity and diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The fact that obesity and diabetes are closely linked is widely appreciated by the general public. Thus, weight loss is an important aspect of controlling diabetes in an obese person. However, the fact that weight gain itself is also important is not very well recognized. Our project will help clarify the mechanisms that make weight gain bad to health, especially from the perspective of heart disease. Thus, it is important that, as obese diabetic patients lose weight, they should also understand that preventing weight regain by exercise and maintaining healthy eating habits is also a very essential goal in the treatment of type 2 diabetes. This project will help explain the science behind weight gain and the increase in risk for heart disease and diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
I have been in the field of treating obesity and diabetes for more than twenty years. I constantly see diabetic patients lose weight and significantly improve their diabetes control. However, it bothers me that many of these patients end up regaining weight and their disease quickly relapses. I have repeatedly witnessed the devastating clinical effects of acute overfeeding on diabetes and heart disease and strongly feel that this area needs to be addressed by medical research.
This award will help our research group establish a practical approach to the study of overfeeding. By accomplishing the goals of this project, we will be able to design future translational clinical and metabolic research in human subjects that specifically addresses the relationships between positive energy balance, weight gain and development of type 2 diabetes.
In what direction do you see the future of diabetes research going?
The future is in the prevention of type 2 diabetes by curtailing the pathophysiological mechanisms that initiate insulin resistance and trigger progression of the disease.
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