Researchers at the University of Toronto have discovered genetic and metabolic markers that could be linked with future onset of type 2 diabetes in women who have previously experienced gestational diabetes.
The finding offers further insight into how the disease develops and why some people are at greater risk than others.
Gestational diabetes is a form of diabetes that occurs in approximately 10 to 20 per cent of pregnancies. While most women recover from the condition after giving birth, they remain at significantly higher risk of developing type 2 diabetes later on in life - with studies estimating that up to 50 per cent of women will go on to develop type 2 diabetes within 10 years.
"Clinically, there's really no way to accurately tell whether or not you will get type 2 diabetes after a gestational diabetes pregnancy," says Michael Wheeler, a professor of physiology in U of T's Temerty Faculty of Medicine.
To help answer this question, Wheeler and his team partnered with Erica Gunderson, a senior research scientist at Kaiser Permanente in California, to look at clinical and metabolic data from over 1,000 women enrolled in the SWIFT study , a study of women, infant feeding and type 2 diabetes after gestational diabetes.
They found that women who developed type 2 diabetes post-pregnancy had a unique profile of metabolites in their blood including, most notably, lower levels of a class of lipids called sphingolipids. This signature was detectable during the early postpartum period when the group of women had recovered from gestational diabetes and were still years away from developing type 2 diabetes.
In their recent study published in the journal Science Advances , the researchers narrowed in on a specific subset of SWIFT study participants - Hispanic women who were at higher risk of both gestational and type 2 diabetes - to understand how reduced sphingolipids contribute to the onset of type 2 diabetes.
By combining metabolic and genetic data, the researchers were able to trace the occurrence of lower sphingolipid levels to a specific variation in the CERS2 gene, which they then recreated in preclinical models that ultimately produced less insulin and were less able to regulate blood sugar levels.
Wheeler, a member of the Banting and Best Diabetes Centre , says that, while these findings point to a potential mechanism driving the evolution of gestational diabetes to type 2 diabetes, there are likely also other important genetic and environmental factors at play.
In another study from Wheeler and the SWIFT study team, published recently in Diabetes/Metabolism Research and Reviews , the researchers describe three unique metabolic profiles among early postpartum women who progressed to type 2 diabetes after experiencing gestational diabetes during their pregnancies.
The study found each profile represented a distinct pathway of progression to type 2 diabetes. One was caused by dysfunction in the pancreatic beta cells that produce insulin, whereas another was driven by insulin resistance, when the body doesn't respond well to insulin in order to move glucose from the blood into cells. The third profile stemmed from a combination of the two.
"These are three different groups of people with a history of gestational diabetes who probably need three different interventions to prevent future type 2 diabetes," says Wheeler, noting the need for a more personalized approach help prevent and manage the disease.
Both studies were led by Saifur Khan, a former postdoctoral researcher in Wheeler's lab who is now a research faculty member at the University of Pittsburgh.
Wheeler says these findings could potentially be used to develop a blood test that a person could take at their first postpartum visit to help determine their risk of type 2 diabetes. His team is also applying the same approach to a different cohort of patients to discover metabolic markers that may help predict gestational diabetes risk early during pregnancy.
In addition to increasing a pregnant person's risk of type 2 diabetes and cardiovascular disease, gestational diabetes can have generational effects on the baby. It increases the risk of: complications during birth; the child being overweight or obese; and diabetes or cardiovascular disease later in life.
"Gestational diabetes is a disease that affects relatively young, otherwise healthy women," Wheeler says. "If you could prevent gestational diabetes, you could prevent disease in both the parent and child, which would be highly impactful."
The research was supported by the Canadian Institutes of Health Research, Diabetes Canada, McKamish Family Foundation, National Institutes of Health and the Samuel and Emma Winters Foundation.
