Snell-Bergeon, Janet K., PhD
Vascular disease, inflammation and hormones in women with type 1 diabetes
General Research Subject: Type 1 Diabetes
Focus: Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Epidemiology, Insulin Action\Insulin Resistance
Type of Grant: Junior Faculty
Project Start Date: January 1, 2010
Project End Date: December 31, 2013
Women with type 1 diabetes (T1D) lose the normal premenopausal protection from heart disease that women without diabetes enjoy. Systemic inflammation, menstrual dysfunction, and insulin resistance are more common in women with T1D than in the general population. There is evidence that hormones in both the growth hormone/IGF-1 and hypothalamic-pituitary-ovary axis may be altered. Few studies have examined the relationship between inflammation, hormones and vascular complications in women with T1D, and this is a novel and important area in need of further research.
This project proposes to address several questions in a prospective study design: 1) differences in inflammation, sex hormones, and insulin-resistance related factors in 164 women (82 with T1D and 82 controls) and their relationship with vascular disease; 2) differences in overnight non-esterified fatty acids, growth hormone and cortisol and their association with insulin sensitivity (skeletal muscle and adipose tissue) using the euglycemic hyperinsulinemic clamp technique in a subset of 48 women (24 with T1D, 24 controls).
The proposed project will significantly advance knowledge regarding the role of inflammation and hormones in complications of T1D and the female loss of protection from vascular disease. The knowledge to be gained from this study can be used to inform future therapy aimed at reducing inflammation and insulin resistance and normalizing hormone levels in women 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?
People with type 1 diabetes have a higher risk of insulin resistance and cardiovascular disease than individuals without diabetes, and the risk is particularly increased in women. The excess cardiovascular risk in women with type 1 diabetes may be caused by sex hormone and growth factor changes, perhaps related to peripheral hyperinsulinemia due to subcutaneous insulin treatment. This project is designed to find out more about differences in growth hormone and sex hormone levels between women with type 1 diabetes and women without diabetes, and the association of these differences with early signs of blood vessel damage and with insulin sensitivity measured by the gold standard, a clamp study.
This project will be unique in that it will follow a cohort of women across an entire menstrual cycle, rather than only measuring sex hormone levels at one point in time. In addition, continuous glucose monitoring will be used to determine whether women who have type 1 diabetes have more glycemic excursions and glycemic variability during the later part of the menstrual cycle, due to changes in hormone levels, and whether glycemic variability is associated with early signs of cardiovascular disease, such as stiffer blood vessels. A smaller group of women will be further studied overnight and during a full day metabolic clamp study, in order to find out if levels of growth hormone and free fatty acids are increased during the night and contribute to the insulin resistance observed in women who have type 1 diabetes.
The role of this project is to identify modifiable risk factors for cardiovascular disease and to promote further understanding of the causes of gender differences in the effect of type 1 diabetes on complications.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Improvements in diabetes management have led to better blood glucose control, and this has reduced the incidence of microvascular complications of type 1 diabetes, such as retinopathy and kidney damage. However, cardiovascular disease in people with type 1 diabetes has not seen such a decrease, and remains the leading cause of death. In particular, the increase in cardiovascular disease in young women with type 1 diabetes is of concern, as type 1 diabetes appears to eliminate the premenopausal protection from heart disease seen in women without diabetes relative to men. The reasons for this loss of protection remain unknown, and so it is important for research to be conducted into potential risk markers or treatments which could reduce the risk of cardiovascular disease in young women with type 1 diabetes. The goal of this project is to identify factors which are associated with increased insulin resistance and arterial stiffness in premenopausal women with type 1 diabetes, with the future goal of improving the identification of women at risk for 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 been involved in diabetes research for a number of years, and I feel that this is an area of great importance from a public health perspective, since diabetes of all types is increasing worldwide. Personally, I am especially interested in improving the health of women, and so identifying the reasons why diabetes increases the cardiovascular disease risk more in women than in men is of great interest to me.
This award will allow me to continue the work I started as part of my doctoral dissertation, and which I have continued as an American Diabetes Association Postdoctoral Fellow. I hope that the research project I will conduct with this Junior Faculty Award will lead to hypotheses which could be tested in a larger study of cardiovascular complications in women with type 1 diabetes.
In what direction do you see the future of diabetes research going?
I see the future of diabetes research as the continued improvement in treatments available to reduce complications, including making insulin delivery and blood glucose regulation more physiologic. In addition, I think important areas of diabetes research are to discover the factors driving the increased incidence of both type 1 and type 2 diabetes, in order to improve our efforts to prevent diabetes.
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