Hu, Frank B., MD, PhD
Lifestyle and environmental determinants of gestational diabetes mellitus and type 2 diabetes mellitus
General Research Subject: Gestational Diabetes
Focus: Epidemiology, Nutrition-Clinical, Obesity, Obesity\Pathogenesis
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2012
Project End Date: June 30, 2016
With rates of overweight and obesity on the rise, conditions such as gestational diabetes mellitus (GDM) and type 2 diabetes (T2DM) are increasing. Women with a history of GDM are at a high risk of being diagnosed with T2DM later in life. These conditions are associated with several medical complications that are both life-threatening and costly. Lifestyle factors, like diet, exercise and obesity, may be important to prevent T2DM after a GDM pregnancy, but little is known at this time. Likewise, environmental contaminants, such as those called endocrine disrupting chemicals (EDCs), could also be important for the development of diabetes, but no data from prospective cohort studies are available.
These two separate research projects, both funded by the National Institutes of Health (NIH), aim to address these important public health concerns. The Diabetes and Women's Health Study recruited 4,500 women with GDM in prior pregnancy. Our research will look at several aspects of lifestyle after pregnancy to determine what exposures lead to a higher risk of developing T2DM. The second study measured EDC levels in urine among 1,700 women in the Nurses' Health Study I to see if concentrations of these contaminants are higher among women with T2DM. Other aspects of this study aim to disentangle the biological process by which these exposures may cause diabetes. Ultimately, by identifying which exposures play a role in the development of diabetes, we may inform policy-makers and develop better recommendations for the prevention of diabetes.
Mentor: Frank B. Hu, MD, PhD Postdoctoral Fellow: Deirdre Tobias, ScD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and/or curing diabetes?
Our research aims to identify modifiable risk factors of type 2 diabetes. Specifically, we will investigate the relationship between diet, physical activity, and exposure to endocrine disrupting chemicals (EDCs) and diabetes in the Nurses’ Health Study I and II, large ongoing observational cohorts with decades of follow-up. EDCs (e.g., bisphenol A [BPA] and phthalates) may lead to the development of diabetes by influencing adipogenesis, inflammation, oxidative stress, steroid-signaling, and hepatic and pancreatic function. While laboratory research provides great insight to these mechanisms, large-scale epidemiologic studies like ours allow these hypotheses to be tested at the population level with clinical diabetes endpoints. Using prospectively collected and stored urine samples, we will measure EDC levels in 1,700 diabetes cases and controls to assess the overall association for these ubiquitous environmental contaminants. Analyses will also explore the interplay between these exposures and liver enzymes on diabetes risk, to investigate liver function as a potential mechanism.
A second research initiative of ours includes the follow-up of 4,500 women with prior gestational diabetes mellitus (GDM) in the Diabetes and Women’s Health Study. GDM is glucose intolerance developed in pregnancy. Although glucose homeostasis is usually resolved after pregnancy, women with prior GDM are at a substantially higher risk of developing type 2 diabetes later in life, compared to women without GDM. Determinants underlying the transition from GDM to type 2 diabetes are not well understood, with limited knowledge of the role that genetic and lifestyle factors may play. These gaps in the literature have motivated us to examine genetic factors and their interactions with modifiable environmental risk factors, including diet and physical activity, in the progression from GDM to type 2 diabetes.
Understanding the role of key modifiable factors ultimately allows us to make important changes to our lifestyle and environment for the prevention of diabetes. Establishing the link between factors like diet, physical activity, and environmental exposures is necessary to inform public health policies and recommendations. Our findings will help identify such exposures and gain a better understanding of the mechanisms by which they act.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Although our research is focused primarily on prevention of type 2 diabetes, our findings may benefit those who have already developed the disease because a healthy diet and lifestyle is also critical for diabetic patients to reduce their risk of developing cardiovascular and other complications. In addition, reducing environmental factors such as exposure to BPA, which has been implicated for obesity and diabetes, is not only important for prevention, but also for management and control of the disease.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
As an epidemiologist, I feel my main role is to build the evidence base for public health recommendations and policies. Research in diabetes epidemiology and prevention is particularly rewarding, given the many recent advances in our understanding of its biology and the large potential lifestyle has for prevention. However, we know there is still a long way to go, which motivates me to investigate novel risk factors and develop creative ways to address this global problem.
This training grant will allow me to provide Dr. Tobias with essential training and research opportunities during her fellowship. Developing the next generation of diabetes researchers is critical to maintain the momentum of science’s advancements. With these rich data resources, she will have a prosperous post-doctoral experience, and one that will help establish her as an independent researcher in the area of diabetes epidemiology and prevention.
In what direction do you see the future of diabetes research going?
Diabetes has reached an epidemic proportion both in the United States and globally, with serious public health consequences and rising economic burden. Fortunately, it has become clear that lifestyle plays a major role, and the fact that this disease is largely preventable gives me great hope for the future of this epidemic. I think two major challenges remain: first, the diabetes epidemic is growing at a rapid pace, especially in developing countries. Long-term population-wide studies need to be in place to track these trends and inform our progress. Simultaneous monitoring of rapid changes in diet and other lifestyle factors also needs to occur. This challenge also includes research to better our understanding of the biological mechanisms between lifestyle and environmental factors and diabetes risk. We need to harness new technologies to better integrate the biological and epidemiologic sciences. Secondly, we need efficient ways of narrowing the gap between research findings and public health practice and policies. Fundamental changes in our lifestyle and food and built environments are needed to curb the global diabetes epidemic, but I am confident we are headed in the right direction.
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