A Step Closer to Predicting Preeclampsia Risk in Diabetes

Norra MacReady

August 15, 2013

Pregnant women with type 1 diabetes have a preeclampsia risk 2 to 4 times higher than that of women without the condition, and now researchers think they have identified some novel markers that may help identify diabetic women most at risk.

Valerie A. Holmes, PhD, senior lecturer at the Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, and colleagues assessed levels of angiogenic and antiangiogenic compounds found in the maternal serum of women with type 1 diabetes in their second trimester and found that abnormal levels of these markers were present in those who developed preeclampsia.

The study, the largest of its kind to date, "would suggest that these markers may have additional predictive risk above and beyond traditional clinical risk factors," said Dr. Holmes. The study was published online August 6, 2013 in Diabetes Care.

"Previous studies have reported altered angiogenic profiles in women at risk of preeclampsia, but few have specifically looked at women with type 1 diabetes," Dr. Holmes told Medscape Medical News in an email. "Our findings, in a carefully characterized population of women with type 1 diabetes, demonstrate that adding measures of [these] factors to established clinical risk factors significantly improves the prediction of preeclampsia. These results are an important step on the road to establishing a preeclampsia 'risk score' for women with type 1 diabetes."

Some Interest in Commercial Development of Tests

The researchers studied 540 women participating in the Diabetes and Preeclampsia Intervention Trial (DAPIT), which enrolled patients from 25 centers across Scotland, Northern Ireland, and England between April 2003 and June 2008. Blood samples were taken at 26 weeks' gestation and analyzed by laboratory staff members who were blinded to each woman's preeclampsia status.

The association of angiogenic factors, such as placental growth factor (PlGF) and antiangiogenic factors — such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) — with preeclampsia was determined through logistic regression analysis adjusted for age, body mass index (BMI), diabetes duration, parity, history of preeclampsia, current smoking, and clinical parameters such as blood pressure, hemoglobin A1c, and renal function.

Of the 540 women included in this study, 94 (17%) developed preeclampsia, and 198 (37%) gave birth prematurely (before 37 weeks' gestation), including 61 women with preeclampsia (65% of women with preeclampsia, compared with 31% of women without preeclampsia; P < .001).

The scientists observed significantly higher levels of sFlt-1 and sEng and significantly lower levels of PlGF, as well as altered ratios of these antiangiogenic and angiogenic factors, during the second trimester in women who later developed preeclampsia compared with those who did not.

"Our findings show that established clinical risk factors, such as previous history of preeclampsia, age, BMI, diabetes duration, parity, blood glucose control, and blood pressure, are indeed reliable indicators of risk in this population," Dr. Holmes told Medscape Medical News. But the results "also suggest that angiogenic factors provide added clinical value when predicting risk," she said.

"These findings need to be validated in another group of women with diabetes before incorporating routine testing into the clinical context. Once they are validated, the next step would be to develop a 'risk score' for women with diabetes, based on a combination of established risk factors and angiogenic-factor results."

The tests for angiogenic factors are currently restricted mainly to research settings, she noted, but there is commercial interest in developing such assays.

"With increasing evidence of the role of angiogenic factors in the pathogenesis of preeclampsia, several companies have developed commercially available assays for at least one of the angiogenic factors we investigated, PlGF, to assist with preeclampsia diagnosis and screening. It is possible that in the future, and with further testing, these assays may emerge as part of routinely available screening test to assist clinicians in determining risk," she said.

This study was funded by grants from the Wellcome Trust and facilitated by the Belfast Health and Social Care Trust, Queen's University Belfast, and by the Manchester Biomedical Research Centre and Greater Manchester Comprehensive Local Research Network. The authors have reported no relevant financial relationships.

Diabetes Care. Published online August 6, 2013. Abstract

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