Researchers from the University of Toronto have identified genetic and metabolic markers that could predict the future onset of type 2 diabetes in women who previously experienced gestational diabetes. This breakthrough provides deeper insight into how gestational diabetes progresses and why some women are more susceptible to developing type 2 diabetes later in life.
Gestational diabetes, a condition that affects approximately 10 to 20 percent of pregnancies, typically resolves after childbirth. However, women who have had gestational diabetes are at a heightened risk of developing type 2 diabetes, with studies showing that up to 50 percent of these women will develop the chronic condition within 10 years.
Michael Wheeler, a professor of physiology at the University of Toronto’s Temerty Faculty of Medicine, emphasized the challenge in predicting which women will develop type 2 diabetes after experiencing gestational diabetes. “Clinically, there’s really no way to accurately tell whether or not you will get type 2 diabetes after a gestational diabetes pregnancy,” Wheeler said.
In an effort to address this gap, Wheeler and his team collaborated with Erica Gunderson, a senior research scientist at Kaiser Permanente in California, to examine clinical and metabolic data from over 1,000 women enrolled in the SWIFT study. This study focuses on the relationship between infant feeding practices and the development of type 2 diabetes following gestational diabetes.
The team discovered that women who developed type 2 diabetes post-pregnancy exhibited a distinct blood metabolite profile, particularly lower levels of sphingolipids—a class of lipids. This signature was detectable even during the early postpartum period, when the women had already recovered from gestational diabetes and were years away from developing type 2 diabetes.
In their study published in Science Advances, the researchers focused on Hispanic women in the SWIFT study, a group at elevated risk for both gestational and type 2 diabetes. By analyzing their genetic and metabolic data, the team traced the reduced sphingolipid levels to a specific variation in the CERS2 gene. Preclinical models with this genetic variation produced less insulin and demonstrated poorer blood sugar regulation, suggesting a potential biological pathway linking gestational diabetes to type 2 diabetes.
While these findings hint at a mechanism driving the transition from gestational to type 2 diabetes, Wheeler noted that genetic and environmental factors likely also play crucial roles.
Additionally, another study led by Wheeler and the SWIFT team, published in Diabetes/Metabolism Research and Reviews, revealed three distinct metabolic profiles among postpartum women who progressed to type 2 diabetes after gestational diabetes. These profiles indicated different pathways to the disease: one linked to pancreatic beta-cell dysfunction, another to insulin resistance, and a third to a combination of both. According to Wheeler, these findings highlight the need for tailored interventions to prevent the development of type 2 diabetes, as each profile represents a different underlying cause.
The research team, which includes Saifur Khan, a former postdoctoral researcher in Wheeler’s lab now at the University of Pittsburgh, believes that these discoveries could lead to the development of a blood test to assess a woman’s risk of type 2 diabetes at her first postpartum visit. Moreover, the same approach is being applied to a new cohort to identify early metabolic markers for gestational diabetes risk.
Gestational diabetes not only increases the mother’s risk of type 2 diabetes and cardiovascular disease, but it also has long-term effects on the child. Children born to mothers with gestational diabetes are at greater risk of complications during birth, obesity, and future diabetes or cardiovascular conditions.
“Gestational diabetes is a disease that affects relatively young, otherwise healthy women,” Wheeler said. “If you could prevent gestational diabetes, you could prevent disease in both the parent and child, which would be highly impactful.”
The research received funding from the Canadian Institutes of Health Research, Diabetes Canada, McKamish Family Foundation, National Institutes of Health, and the Samuel and Emma Winters Foundation.
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