Does Gestational Diabetes Per Se Up Long-term Cardiovascular Risk?

Women with a history of gestational diabetes are at greater risk for cardiovascular disease (CVD) events — especially myocardial infarction (MI) — later in life compared with women who do not develop gestational diabetes during pregnancy, even though the absolute risk is low, indicates a new analysis from the prospective Nurses' Health Study II.

The study was published online October 16 in JAMA Internal Medicine.

Although prior studies have identified gestational diabetes as a risk factor for intermediate markers of CVD risk — such as subsequent hypertension, dyslipidemia, and type 2 diabetes — the relationship between gestational diabetes and subsequent CVD had not previously been prospectively evaluated with careful control for common risk factors or mediating lifestyle characteristics, say Deirdre Tobias, ScD, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues.

Their work confirms the higher rates of CVD among women with gestational diabetes who later develop type 2 diabetes compared with women who didn't have either, note Erica Gunderson, PhD, Kaiser Permanente Northern California, Oakland, and Marc Jaffe, MD, Kaiser Permanente South San Francisco Medical Center, California, in an accompanying editorial.

And a "new finding" is "a borderline 30% higher relative risk of CVD events in women with a history of gestational diabetes who did not subsequently develop type 2 diabetes," indicating "that a history of gestational diabetes may increase CVD risk distinct from overt [type 2] diabetes or differences in lifestyle behaviors," they stress.

However, after adjustment for relevant risk factors, this was attenuated to a 20% increased relative risk, so women who maintain a healthy lifestyle through their middle years may reduce their CVD risk despite having a history of gestational diabetes.

Overall, 6% of Pregnancies Affected by Gestational Diabetes

Out of 89,479 parous women in the study, 5.9% had a history of gestational diabetes in at least one pregnancy at baseline or follow-up. During a median follow-up of 25.7 years, the researchers documented 1161 CVD events — 612 MIs and 553 strokes.

"Compared with parous women without gestational diabetes, those with a history of gestational diabetes experienced a 60% greater [absolute] risk of CVD during follow-up," the authors report.

The risk was attenuated when adjusted for risk factors including behavioral, such as weight gain, smoking, quality of diet, alcohol consumption, physical activity, and aspirin use; however, women with a history of gestational diabetes still had a 29% higher risk of a CVD event over long-term follow-up relative to women with no history of gestational diabetes, the authors report.

Investigators also assessed history of gestational diabetes and future risk of MI or stroke separately.

In a fully adjusted analysis, a history of gestational diabetes significantly increased the risk of MI by 45% (P = .02), but not stroke (hazard ratio [HR], 1.10; P = .60).

Gestational Diabetes, Diabetes, and CVD Risk

As is well established, a history of gestational diabetes also increases a woman's risk of type 2 diabetes. In this long-term analysis, 19% of women with a history of gestational diabetes subsequently developed type 2 diabetes compared with 4.8% of women with no prior history of gestational diabetes.

"The fully adjusted model indicated a greater than threefold elevated risk of CVD for women with both gestational diabetes and type 2 diabetes, or type 2 diabetes only, vs women without any diabetes," the investigators observe (HR, 3.71 and 3.74, respectively).

Importantly, however, after adjustment for weight and other lifestyle factors, women with a history of gestational diabetes who did not eventually develop type 2 diabetes were not at increased risk for CVD events, they add.

This finding in particular indicates that women who maintain a healthy lifestyle through midlife may reduce their CVD risk despite having a history of gestational diabetes, the investigators suggest.

The protective effect of lifestyle among women with a history of gestational diabetes was further reinforced by the finding that women with a diet-quality score in the top half, nonsmokers, those who maintained a healthy weight throughout the 25.7-year follow-up, and those who exercised at least 500 MET-min/week were not at increased risk of CVD events either.

"Furthermore, among women with at least three of these four healthy lifestyle factors, a history of gestational diabetes was not associated with CVD risk," the authors point out.

In contrast, women with a history of gestational diabetes who engaged in two or fewer of these healthy lifestyle behaviors had a 57% higher risk of a CVD event later in life, they add.

Prepregnancy weight also influenced CVD risk over time, as women with a history of gestational diabetes who were overweight or obese prior to becoming pregnant were over twice as likely to experience a CVD event (HR, 2.04) compared with those with no history of gestational diabetes.

"Collectively, these findings support the role of lifestyle for the prevention of CVD among high-risk women with a history of gestational diabetes, although the small absolute rate increase of approximately 0.3 CVD events per 1000 person-years observed for those with a history of gestational diabetes among these younger, predominantly white women may preclude widespread costly long-term interventions," the authors say.

They add that prospective studies with carefully phenotyped CVD markers pre- and postpregnancy are needed to "tease out whether gestational diabetes itself induces adverse CV changes, is simply a marker for underlying high risk, or is some combination of these."

Be More Vigilant With Women Who've Had Gestational Diabetes

In an accompanying editorial, Drs Gunderson and Jaffe say that say that several years ago the American College of Obstetricians and Gynecologists along with the National Diabetes Education Program called for primary-care physicians to screen women with a history of gestational diabetes before and after pregnancy to improve clinical outcomes.

"Gestational diabetes identifies young women who may benefit from heightened vigilance after pregnancy," the editorialists suggest.

The study was supported by the National Institutes of Health. Dr Zhang is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant financial relationships. Dr Gunderson has received funding from Janssen Pharmaceuticals. Dr Jaffe has no relevant financial relationships.

JAMA Intern Med. Published online October 16, 2017. Abstract, Editorial

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