Study explores link between sex hormones and heart disease risk in type 2 diabetes

People with type 2 diabetes face a higher risk of heart attacks, strokes and other cardiovascular problems, according to the National Institutes of Health. These risks also differ between women and men, but doctors don't fully understand why. In a new Johns Hopkins Medicine-led study, researchers explore whether sex hormones like testosterone and estradiol help explain these differences.

We are very interested in understanding why women who have diabetes have a greater risk for heart disease compared to men. Sex hormones matter and could explain some of the differences in heart disease outcomes in women and men."

Wendy Bennett, M.D., M.P.H., lead researcher, associate professor of medicine, Johns Hopkins University School of Medicine

The study was published today in Diabetes Care and supported by funding from the National Institutes of Health.

Researchers used the data from a study called Look Ahead focused on how weight loss in people with type 2 diabetes shaped heart health outcomes. After the study ended, participants continued to receive follow-up care. For the new study, researchers evaluated blood samples of participating patients and analyzed sex hormone levels at the beginning of the trial and one year after enrollment.

"We were able to see whether the changes in hormones affected their heart disease risk," Bennett says. "We saw that there were differences in the male participants. If they had higher testosterone when they joined the study, they had a lower risk. If they had increases in estradiol levels after one year in the study, they also had a higher risk of heart disease."

In women, the researchers did not find meaningful links between these hormone levels and cardiovascular outcomes.

"Results from this study contribute to our understanding of how tracking sex hormones in people with diabetes could complement what we already know about traditional heart disease risk factors [like smoking and cholesterol levels]," Bennett says. "The results could help clinicians personalize heart disease prevention strategies in the future."

Bennett says the next steps in this research are to examine other factors and outcomes, including how weight loss and hormones affect bone health in people with diabetes. The researchers hope to determine who is at risk of fractures and why. They are also identifying new studies examining how hormone declines in the menopausal transition, also known as perimenopause, and how hormone declines might affect cardiovascular risk, especially in people with chronic illnesses like diabetes. 

Other researchers include Teresa Gisinger, M.D., Ph.D., Jiahuan Helen He, M.H.S., Chigolum Oyeka, MBBS, M.P.H., Jianqiao Ma, ScM, Nityasree Srialluri, M.D., M.S., M.H.S., Mark Woodward, Ph.D., Erin D. Michos, M.D., M.H.S., Rita R. Kalyani, M.D., M.H.S., Jeanne M. Clark, M.D., M.P.H., Alexandra Kautzky-Willer, M.D., and Dhananjay Vaidya, MBBS, Ph.D., M.P.H.

Clark reports serving as a scientific advisor to Boehringer Ingelheim and receiving writing support from Novo Nordisk in the last three years. Unrelated to this work, Michos has served as a consultant for Amgen, Arrowhead, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Life Science, Esperion, Ionis, Eli Lilly, Medtronic, Merck, New Amsterdam, Novartis, Novo Nordisk, and Zoll.

This work was funded by two National Institute of Health Diabetes and Digestive and Kidney Diseases grants, R01DK127222 and U01DK57149.