High-Normal Glucose Challenge Tests in Pregnancy May Predict Future Risk of CV Events

For many women, the syrupy orange drink given as part of a standard glucose challenge test late in the second trimester of pregnancy is easily forgotten, especially if the test results are normal. But a new study suggests that the findings from those tests may be more important to long-term cardiovascular health than previously recognized.

While gestational diabetes has been linked to later cardiovascular risk, including in a recent large US study, the new data indicate that even measurements on the higher end of normal could predict women at increased risk of developing cardiovascular disease in the years after pregnancy.

“As it is, we struggle as clinicians to take care of women who are diagnosed with gestational diabetes, conveying that this is a long-term risk and it's important to maintain healthy lifestyles and health behaviors into the future,” study co-author Baiju R. Shah, MD (University of Toronto, Canada), said in an interview with TCMTD. “For women who screen normal and don't have gestational diabetes, the message is always that everything is fine, and that they don't need to think about it again. But what we're showing here is that's not necessarily the case.”

In a study published online ahead of print in the Lancet last month, Shah and Ravi Retnakaran, MD (Mount Sinai Hospital, Toronto, Canada), looked across the spectrum of plasma glucose results in a large group of pregnant women and found that even those on the higher end of normal had an increased risk of cardiovascular events in the ensuing years compared with women at the lower end of normal.

For women who screen normal and don't have gestational diabetes, the message is always that everything is fine, and that they don't need to think about it again. But what we're showing here is that's not necessarily the case. Baiju R. Shah

The population cohort study included 259,164 Canadian women, followed for a median of 3.9 years after a pregnancy-related glucose challenge test. Of these, 5.3% had a result of 8.0 mmol/L or higher. Gestational diabetes is generally diagnosed at a 1-hour postchallenge plasma glucose measurement of 11.1 mmol/L or higher, with measurements between 7.8 mmol/L and 11.0 mmol/L considered to be indicative of impaired glucose tolerance, or prediabetes.

A Continuous Measure of Metabolic Compensation

Not surprisingly, cardiovascular events in the study population of pregnant women in their 20s and 30s were rare, occurring in just 0.5%. However, when patients were stratified by glucose measurements, each 1-mmol/L increase in glucose above 7.1 mmol/L was associated with a 13% greater risk of cardiovascular disease. The association remained after adjustment for multiple factors including parity, gestational diabetes in a prior pregnancy, hypertension, preeclampsia, preterm delivery, and postpartum progression to diabetes.

“Furthermore, this relationship persisted even after excluding the women who had gestational diabetes,” Retnakaran and Shah write. “It thus emerged that the glucose challenge test provided a continuous measure of maternal glycemia in pregnancy that related to subsequent risk of cardiovascular disease in both the general obstetrical population and the subpopulation of women without gestational diabetes.”

The association also persisted after additional adjustments, including restricting outcomes to only MI and stroke as well as excluding all twin and multiple gestation pregnancies. Compared with those who had measurements of ≤ 7.1 mmol/L, women who had an abnormal glucose measurements ≥ 7.8 mmol/L had a significant increase in cardiovascular disease (HR 1.94; 95% CI 1.29-2.92), as did women with measurements between 7.2 mmol/L and 7.7 mmol/L (HR 1.65; 95% CI 0.99-2.76).

To TCTMD, Shah said the study emphasizes that the information obtained from the test can help women and their physicians foresee their long-term cardiovascular profile. In a sense, he added, pregnancy can be considered a metabolic stress test that gives a glimpse into the ability or inability of an individual’s metabolism to compensate.

“If your underlying metabolism is one that’s going to lead you to have high blood sugar in pregnancy, it makes sense that it also probably is going to lead you to have high blood sugar in the future, and maybe hypertension and cardiovascular disease as well,” Shah noted.

The study also raises an interesting conundrum since glucose tests in pregnancy are ordered by a woman’s ob-gyn, and that information may never reach their other healthcare providers if gestational diabetes is not diagnosed.

“The fact that [the test] was abnormal or even on the high end of normal needs to be fed back to the primary care physician, and to the patient of course, so they can be aware of it,” Shah said. “It is a marker of increased risk and therefore it’s important to think about prevention and healthy behaviors into the long term. Right now, the way our healthcare system is structured, a lot of this information just disappears and it isn't readily accessible down the line. We think just making sure it gets copied to the primary care provider, something as simple as that, could make a big difference for prevention.”