"We are very interested in understanding why women who have diabetes have a greater risk for heart disease compared to men," says lead researcher Wendy Bennett, M.D., M.P.H., an associate professor of medicine at Johns Hopkins University School of Medicine. "Sex hormones matter and could explain some of the differences in heart disease outcomes in women and men."

The research was published Diabetes Care and received funding support from the National Institutes of Health.

Tracking Hormone Levels Over Time

To conduct the study, researchers analyzed data from the Look Ahead study, a long-term project that examined how weight loss affected heart health in people with type 2 diabetes. Even after the original trial ended, participants continued to receive follow-up care, allowing researchers to collect additional health information over time.

For the current analysis, the team examined blood samples from participants to measure sex hormone levels. These samples were taken at the start of the study and again one year after enrollment, giving researchers insight into how hormone levels changed and whether those changes were linked to future heart disease risk.

Different Hormone Patterns in Men and Women

"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."

Among female participants, however, researchers did not observe clear connections between hormone levels and cardiovascular outcomes. This suggests that hormones may influence heart disease risk differently depending on sex, or that other biological and clinical factors may play a larger role for women with diabetes.

Toward More Personalized Heart Disease Prevention

"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."

Looking ahead, Bennett says the research team plans to explore additional health outcomes related to hormones and diabetes. These include studying how weight loss and hormone changes affect bone health, as well as identifying which patients may be at higher risk for fractures and why. Researchers are also preparing new studies focused on hormone declines during the menopausal transition, also known as perimenopause, and how those hormonal changes may influence cardiovascular risk, particularly in people with chronic conditions such as diabetes.

Study Team, Disclosures, and Funding

The study's coauthors 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 research, 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 research was funded by two National Institute of Health Diabetes and Digestive and Kidney Diseases grants, R01DK127222 and U01DK57149.