Antioxidants may protect women with diabetes against estrogen’s cardiovascular effects

Higher estrogen levels, which typically protect against heart disease, multiply cardiovascular risk in women of child-bearing age with diabetes, according to researchers at the Georgia Prevention Institute and Department of Population Health Sciences, Medical College of Georgia at Augusta University, Augusta, GA.

“When you have diabetes, estrogen turns into a bad guy,” said principal investigator Ryan A. Harris, PhD, director, Laboratory of Integrative Vascular and Exercise Physiology, Medical College of Georgia. “It actually causes blood vessel constriction when you have high levels of estrogen.”

In a new study currently under way, the team is assessing blood vessel health in women with type 1 diabetes (T1D) during the natural peaks and troughs in estrogen levels over the course of the menstrual cycle. The researchers are also looking at whether two types of antioxidants—resveratrol or a cocktail of antioxidant vitamins C and E along with alpha lipoic acid—can restore the cardioprotective effect of estrogen.

The team hypothesized that resveratrol, which is found in red grapes, berries, and peanuts, acts as an antioxidant by directly activating the protein Sirt1. This protein then reduces reactive oxygen species produced by the endothelial lining of blood vessels and increases levels of nitric oxide, a powerful dilator. Sirt1 rises during high-estrogen days of the menstrual cycle; however, this rise is diminished in women with diabetes.

For this study, the researchers are recruiting 90 premenopausal women with T1D, 30 healthy premenopausal women, and 45 demographically matched men with T1D. The participants are aged between 18 and 40 years and are not diagnosed with cardiovascular disease or diabetes complications.

The researchers speculate that estrogen rapidly ages the cardiovascular system. They’ve gathered early evidence that indicates estrogen not only increases damaging oxidative stress levels, but also impairs the dilation of blood vessels in those with diabetes.

In an in vitro experiment in a Petri dish, a normal blood vessel dilates when estrogen is placed on it, whereas a diabetic blood vessel will contract when given estrogen.

“Once we can identify why estrogen acts like a bad guy, why estrogen causes vasoconstriction instead of vasodilation in these women,” said Dr. Harris, “then we could introduce non-pharmacological treatments throughout the menstrual cycle that could ultimately reduce their cardiovascular disease risk.”