The Role of Angiogenic and Antiangiogenic Factors in the Second Trimester in the Prediction of Preeclampsia in Pregnant Women With Type 1 Diabetes

  1. for the Diabetes and Preeclampsia Intervention Trial (DAPIT) Study Group
  1. 1Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom
  2. 2Department of Obstetrics, St. Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
  3. 3Department of Diabetes, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
  4. 4Department of Diabetes, St. John’s Hospital at Howden, West Lothian, United Kingdom
  5. 5Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom
  1. Corresponding author: Valerie Holmes, v.holmes{at}


OBJECTIVE To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial.

RESULTS Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120–423] vs. 365 pg/mL [237–582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108–3,393] vs. 1,193 pg/mL [844–1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9–7.9] vs. 5.1 ng/mL[(4.3–6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17–71] vs. 71 [44–114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4–15.7] vs. 3.1 [1.8–5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001).

CONCLUSIONS These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

  • Received April 22, 2013.
  • Accepted May 31, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

This Article

  1. Diabetes Care
  1. All Versions of this Article:
    1. dc13-0944v1
    2. 36/11/3671 most recent