Gestational Diabetes Increases Macrovascular Risk

Clinicians should follow women who develop gestational diabetes and intervene early to reduce risk for cardiovascular diseases.

Gestational diabetes mellitus (GDM) may occur in some women late in pregnancy as a combined result of insulin resistance and insufficient β-cell function. Since women who develop GDM have an elevated lifetime risk of both type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD),1 postpartum management should include regular testing for T2D,2 but it has been unclear if the risk of CVD was linked to T2D, or other factors.

Women who developed GDM will carry an increased risk for macrovascular disease, including CVD and coronary artery disease (CAD), regardless of their diabetes status. In contrast, the risk of microvascular outcomes, including retinopathies, renal dialysis, and foot ulcers, has been increased only among women who developed T2D, according to a study published in Diabetes Care.3

“What we have shown is that if women have a history of GDM, they are still at risk of developing CVD, even if they do not progress to T2D,” the study’s lead author, Ravi Retnakaran, MD, MSc, from Mount Sinai Hospital in Toronto, Canada told EndocrineWeb. “Progression to T2D is clearly the biggest risk, but even if they don’t progress, these women are still at risk of cardiovascular outcomes.”

Clinical Significance of GDM on Cardiovascular Outcomes

Defining the relationship between cardiovascular outcomes and T2D may help to determine the optimal regimen for postpartum surveillance of women who have had GDM. If the increase in CVD risk in women with a history of GDM is only present in those who later develop T2D, then periodic testing of their glucose tolerance may also effectively screen for women with increased vascular risk. If cardiovascular outcomes and T2D are not strongly linked, then diabetes status may not identify women with increased vascular risk.

From this population-based cohort, the researchers calculated the risk of micro- and macrovascular outcomes for women in 4 different exposure groups: GDM only, GDM and diabetes, diabetes only, and neither condition. They found that women with T2D were at greater risk of microvascular events than women without T2D, regardless of their GDM history. Previous GDM, however, increased the risk of macrovascular events like CVD and CAD in all women, but more so for those who developed T2D. The hazard ratios reported for different cardiovascular outcomes among women with and without GDM and T2D are shown in Table 1.

“These results tell clinicians that they need to consider the possibility that if a woman had GDM, she is at risk of developing CVD in the future,” Dr. Retnakaran explained to EndocrineWeb. “These results raise the question of whether the sentinel event of being diagnosed with GDM should result in closer surveillance of cardiovascular risk factors and earlier intervention.”

“This study clearly defines that women with GDM have an increased lifetime risk of cardiovascular disease, and shows that it is the development of T2D that leads to an increased risk of microvascular disease later in life,” said J. Michael Gonzalez-Campoy, MD, PhD, the Medical Director and CEO of the Minnesota Center for Obesity, Metabolism and Endocrinology in Eagan, Minnesota, who was not involved in the study but commented as a member of the EndocrineWeb editorial board.

“Clinicians should continue to educate women with GDM about their lifelong health risks, and, on a yearly basis, women with a history of GDM should have their glycemic state redefined and other risk factors for cardiovascular disease addressed,” said Dr. Gonzalez-Campoy.

Because the absolute number of cardiovascular outcomes in this population of women was few, it is unclear whether early screening and risk factor modification would be cost effective in practice. Instead, the authors suggested that GDM and T2D histories become a prominent factor in the evaluation and modification of risk factors in women when they reach the menopausal transition given their increased risk for CVD will rise.

“Early intervention in the progression of disease is key,” noted Dr. Gonzalez-Campoy. “Women with gestational diabetes, due to the stress of a pregnancy, declare themselves early, and this allows for clinicians to identify women at risk for metabolic diseases and initiate treatment early.”

Study Details

A total of 1,515,079 women who had live birth pregnancies in Ontario, Canada, between 1994 and 2014 were stratified into 4 groups based on whether or not they developed GDM and T2DM. Women were excluded if they were diagnosed with pregestational diabetes or previous CVD. Microvascular and macrovascular outcomes were reported over a median follow up of 10 years. In women who had multiple qualifying pregnancies during the study period, 1 pregnancy was chosen at random to be included in the analysis.

Finally, because recommended postpartum testing for diabetes status has been inconsistently performed in real-world practice, the authors suggested that this sample likely underestimates the number of women with GDM who went on to develop T2D later. However, the possibility of undiagnosed T2D in the study population does not change the authors’ interpretation of the data.

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