(Vienna, 26-01-2026) – People with type 2 diabetes have a significantly increased risk of cardiovascular disease. Women are relatively more affected than men, although the disease occurs with similar frequency in both sexes. The biological factors contributing to these differences are not yet fully understood. A study recently published in Diabetes Care, led by Johns Hopkins University with significant participation from the Medical University of Vienna, has now investigated the link between sex hormones and long-term cardiovascular events in people with type 2 diabetes.
The research is based on data from the US Look-AHEAD study (Action for Health in Diabetes), a randomised long-term study initiated by the National Institutes of Health and conducted since 2001, which investigated the effects of intensive lifestyle intervention involving dietary changes and physical activity in adults with type 2 diabetes.
The current analysis included 2,260 men and postmenopausal women with type 2 diabetes and overweight or obesity. Blood levels of testosterone, estradiol and sex hormone-binding globulin (SHBG), a transport protein that influences how much of a hormone is biologically active in the body, were determined. The measurements were taken at the start of the study and one year after the start of the lifestyle intervention. The participants were then observed over a period of around twelve years, during which cardiovascular events such as heart attacks, strokes, cardiovascular deaths or hospitalisations due to angina pectoris were recorded.
In men, several associations between hormones and cardiovascular risk were found. For example, a higher risk of subsequent cardiovascular events was associated with lower testosterone levels at the start of the study. The degree of weight loss also played a role: men who lost at least seven percent of their body weight in the first year had a lower long-term cardiovascular risk when SHBG levels increased. In men with lower weight loss, however, an increase in estradiol levels was associated with an increased risk. In women, no statistically significant associations were found between the hormone levels examined and cardiovascular events.
Further research needed
"Our findings show that sex hormones in men with type 2 diabetes may be associated with long-term cardiovascular risk, particularly in relation to weight changes," says study leader Wendy Bennett of Johns Hopkins University in Baltimore (USA). "They thus complement the known risk factors such as smoking or elevated cholesterol levels, which are already taken into account in clinical practice."
First author Teresa Gisinger from MedUni Vienna, who was working at Johns Hopkins University at the time of the study, emphasises the cautious interpretation: "The observed correlations do not allow any conclusions to be drawn about cause and effect. However, they show that hormonal changes following a lifestyle intervention could provide additional information about cardiovascular risk. "
Alexandra Kautzky-Willer from the Medical University of Vienna, who has been researching gender-specific aspects of diabetes and cardiovascular disease for many years, was also involved in the study. The authors emphasise that further research is needed before sex hormones can be used for individual risk assessment in clinical practice.
Publication: Diabetes Care
Sex Hormones and Cardiovascular Risk in Type 2 Diabetes: Cohort Study of the LookAHEAD Trial.
Teresa Gisinger, Jiahuan Helen He, Chigolum P. Oyeka, Jianqiao Ma Nityasree Srialluri, Mark Woodward, Erin D. Michos, Rita R. Kalyani, Jeanne M. Clark, Alexandra Kautzky-Willer, Dhananjay Vaidya and Wendy L. Bennett.
DOI: 10.2337/dc25-2465