GDM Ups Cardiovascular Risk Whether or Not Later Diabetes Develops

Veronica Hackethal, MD

November 21, 2016

Women with a history of gestational diabetes (GDM) are at increased risk of cardiovascular events even if they don't subsequently develop type 2 diabetes after their affected pregnancy, results from a new Canadian study indicate.

Having gestational diabetes increases a woman's risk of developing type 2 diabetes during her lifetime by about sevenfold, an association that is already well recognized, say Ravi Retnakaran, MD, and Baiju R Shah, MD, PhD, of the University of Toronto, Ontario, in their paper published online November 7 in Diabetes Care.

And more recently, it has emerged that women with prior GDM have an increased risk of cardiovascular disease per se, compared with their peers who did not develop gestational diabetes, but until now it had not been known whether this higher risk was dependent on the development of type 2 diabetes.

"This study showed that women with gestational diabetes mellitus have an increased risk of macrovascular complications whether or not they develop type 2 diabetes. That risk is highest in those who develop type 2 diabetes, which is not surprising. But even if they don't develop type 2 diabetes, they still have an increased risk of macrovascular outcomes," Dr Retnakaran told Medscape Medical News.

"The message from this study is that if you have GDM during pregnancy you need to know that you're at risk for type 2 diabetes and CVD complications in the future," Dr Retnakaran emphasized.

The study also indicates that women with GDM who subsequently develop type 2 diabetes are at increased risk of microvascular complications, such as diabetic retinopathy and nephropathy, but if they have only GDM they do not seem to be at greater risk of these complications, another important clinical finding, he added.

Only Those With GDM and T2D Developed Microvascular Complications

In the study researchers used administrative databases to identify all women in Ontario, Canada without diabetes or CVD before pregnancy and who had given birth to a live infant between April 1994 and March 2014 (n=1,515,079).

The analysis separated women into four groups:

  • Women with GDM who went on to develop type 2 diabetes (n=15,585).

  • Women with GDM who did not develop type 2 diabetes (n=41,299).

  • Women without GDM who developed type 2 diabetes (n=49,397).

  • Women without GDM who did not develop type 2 diabetes (n=1,408,798).

Over a median follow-up of 10 years, the researchers evaluated retinopathy procedures (photocoagulation, vitrectomy) and nephropathy procedures (dialysis), as well as the likelihood of macrovascular complications such as coronary artery and cerebrovascular disease events.

Results showed that, regardless of whether women had GDM, if they developed type 2 diabetes they had increased risk of micro- and macrovascular complications.

Among women with GDM, only the group who also developed type 2 diabetes had increased risk of microvascular complications, including a greater-than-fourfold increased risk for vitrectomy/photocoagulation (hazard ratio [HR], 4.49), a more-than-seven-times increased risk of renal dialysis (HR, 7.52), and over-four-times increased risk of hospitalization for foot infection (HR, 4.32) (all P < .0001), compared with women without GDM who did not develop type 2 diabetes.

Prioritize and Support Breastfeeding to Reduce Risk

And as would be expected, women who had GDM and developed type 2 diabetes had almost three-times increased risk of a CVD event (HR, 2.82; P < .0001), and over-three-times increased risk of a CAD event (HR 3.54; P < .0001), compared with women without GDM who did not develop diabetes.

But even those women who had GDM but did not develop type 2 diabetes had higher risks of macrovascular events — a 30% increased risk of a CVD event (HR, 1.30; P = .008) and 41% increased risk of a CAD event (HR, 1.41; P = .005) compared with women without GDM or type 2 diabetes.

While results were adjusted for age, income, and region of residence, the analysis could not adjust for other important confounders like race, body mass index, weight gain, or the presence of other comorbid conditions such as polycystic ovary syndrome and certain autoimmune diseases, Erica Gunderson, PhD, MPH, of Kaiser Permanente Northern California, Oakland, California, pointed out in an email to Medscape Medical News.

And importantly, the study could not evaluate the impact of lactation and breast feeding on GDM and diabetes progression. Breastfeeding for over 5 months is linked to a 50% reduced incidence of type 2 diabetes in women who have had GDM, according to Dr Gunderson.

"Breastfeeding promotion is a much higher priority than diet and physical activity during the first year postpartum and is necessary to accomplish the metabolic reset for women to recover from the hyperlipidemia, hyperinsulinemia, and hyperglycemia of normal pregnancy," she commented.

However, too many women are not able to breastfeed because of lack of sufficient paid family leave in the United States in particular, plus there are other barriers, she emphasized.

"Women should not be expected to put their families in financial jeopardy by unpaid leave. The system currently does not support breastfeeding for families who have the greatest need for benefits to prevent diabetes in women and their children," she stressed.

Important to Test Women With GDM for Subsequent Type 2 Diabetes

Another issue is testing for progression of diabetes in the postpartum period.

The American Diabetes Association and the Canadian Diabetes Association recommend postpartum glucose tolerance testing in women with a history of GDM.

"This study emphasizes the importance of that test. Women who developed diabetes after GDM had the highest rates of everything, macrovascular as well as microvascular outcomes," Dr Retnakaran stressed.

These women with GDM have been shown a "window" into their future health risk, he explained.

The fact that many women do not receive the recommended postpartum screening for diabetes is one of the "great missed opportunities" in clinical medicine, according to Dr Retnakaran.

Dr Gunderson believes there "needs to be a simple test to predict future risk of progression to type 2 diabetes within several weeks after delivery [in those who've had GDM] that has high accuracy and is simple for women to do." More studies are needed on this, she stressed.

Also, said Dr Retnakaran, "as clinicians we need to recognize that if a woman has a history of GDM, we need to consider the possibility that she could be at risk of developing CVD" even if she doesn't develop diabetes.

"The next step would be asking what's determining that increased risk and what can be done about it clinically," he concluded.

Dr Retnakaran is supported by a Heart and Stroke Foundation of Ontario Mid-Career Investigator award, and his research program is supported by an Ontario Ministry of Research and Innovation Early Researcher award. Dr Shah is supported by a Canadian Institutes of Health Research New Investigator award. Dr Gunderson reports no relevant financial relationships.

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Diabetes Care. Published online November 7 2016. Abstract

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