Alman, Amy , PhD
Epicardial fat and inflammatory mediators in the excess risk of coronary artery calcification among women with type 1 diabetes
General Research Subject: Type 1 Diabetes
Focus: Epidemiology, Obesity\Pathogenesis
Type of Grant: Clinical Science and Epidemiology
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Diabetes Type: Type 1 diabetes
Women with type 1 diabetes are at increased risk of cardiovascular disease, but the mechanisms are not well understood. The recognition that fat tissues in different parts of the body may function differently is leading to new areas of research on how different areas of fat can increase the risk of cardiovascular disease. This may play an important role in the excess risk of cardiovascular disease experienced by women with type 1 diabetes for the following reasons: 1) fat is distributed differently in women compared to men (pear-shaped versus apple-shaped), 2) fat tissues have been shown to play a role in insulin resistance and to increase inflammation and these have been associated with cardiovascular disease, and 3) different fat tissues have different effects on cardiovascular disease risk. These observations have led to the hypothesis for this project: that epicardial fat, a type of fat that surrounds the coronary arteries in the heart, plays a role in the increased risk of cardiovascular disease seen in women with type 1 diabetes.
Cardiovascular disease is a significant cause of morbidity and mortality in those with diabetes. Understanding the risk factors better can help to identify those at greater risk and lead to new targeted interventions and treatments. Reductions in epicardial fat have been demonstrated with changes in diet and exercise, so this work can lead to significant improvements in the long-term health of those with type 1 diabetes.
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 is investigating the role of the fat that surrounds the coronary arteries, called epicardial fat, in the excess risk of coronary artery calcification in women with type 1 diabetes. Research has shown that visceral fat (fat surrounding the organs) is more strongly associated with cardiovascular disease than the fat directly under the skin (subcutaneous fat), and that the distribution of fat in the body is important in the risk for disease. In women without diabetes, it is thought that the peripheral fat distribution may play a cardioprotective role in energy metabolism, whereas in men, the central fat distribution may play a role in increased risk. Women with diabetes have been shown to have a much greater relative risk of cardiovascular disease compared to women without diabetes, so this observation suggests that an altered fat distribution or function in diabetes may play a role in this increased risk.
Since epicardial fat has been shown to be strongly associated with cardiovascular disease risk, and to produce more inflammatory mediators than other fat depots, we have hypothesized that the function and distribution of epicardial fat in women with type 1 diabetes may be altered in a way that increases the risk of plaque deposition in the coronary arteries, leading to increased cardiovascular disease. The results from this study will increase the knowledge of the functions of specific fat depots and inflammation in cardiovascular disease risk in those with diabetes, which could lead to targeted interventions to reduce epicardial fat and the inflammatory mediators that it produces.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
This study will lead to better understanding of the mechanisms involved in the development of cardiovascular disease in those with diabetes. Since cardiovascular disease is the leading cause of morbidity and mortality in those with diabetes, understanding risk factors for the development of the disease is critical. Once we understand the risk factors, we can begin to target them for prevention and treatment, which will result in better care, fewer complications, and more options for prevention and treatment of cardiovascular disease.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I have several family members with diabetes, both type 1 and type 2. My grandmother, who eventually succumbed to lung cancer, struggled to manage her type 1 diabetes as she got older, particularly as other comorbidities began to increase the difficulty in managing the disease. She was found several times nearly in a diabetic coma. I remember her as a strong woman who managed her disease with remarkable ease, that is until her health declined, and then the diabetes became a major factor in the decrease in her quality of life. I have always wondered how much of a role diabetes played in her other comorbidities, and her eventual demise.
From a research standpoint, I am very interested in understanding the biologic mechanisms involved in cardiovascular disease risk. This award provides me with a tremendous advantage to not only launch my career in studying the mechanisms of cardiovascular disease risk in diabetes, but to collect longitudinal data on a well-defined cohort that will be able to go beyond the objectives of this project and become the foundation of many future projects as well.
I think this project has implications for not just epicardial fat in women with type 1 diabetes, but also in understanding how fat depots can differentially affect cardiovascular disease risk. This has implications for men, women, type 1 diabetes, type 2 diabetes, and those without diabetes. Therefore, this award opens up many new avenues for future research and collaborations. Considering the rising epidemic of obesity, better understanding of the function and relationship of fat depots to complications of diabetes is critical, and this award will not only collect very meaningful and valuable data in addressing some of these questions, but also act as a springboard for a career in researching these areas.
In what direction do you see the future of diabetes research going?
As an epidemiologist, I see the future of diabetes research in understanding the mechanisms underlying the onset, progression and complications of diabetes. If we understand the etiology better, we can come up with ways to slow or prevent the onset of disease and progression, and prevent the complications.
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