Circulating Levels of the Antiangiogenic Marker Soluble FMS-Like Tyrosine Kinase 1 Are Elevated in Women With Pregestational Diabetes and Preeclampsia
Angiogenic markers in preeclampsia and preexisting diabetes
- Allison Cohen, MD123,
- Kee-Hak Lim, MD34,
- Young Lee, MD34,
- Sarosh Rana, MD45,
- S. Ananth Karumanchi, MD134 and
- Florence Brown, MD123
- 1Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- 2Joslin Diabetes Center, Boston, Massachusetts
- 3Harvard Medical School, Boston, Massachusetts
- 4Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- 5Brown University, Providence, Rhode Island
- Address correspondence and reprint requests to Florence Brown, MD, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: florence.brown{at}joslin.harvard.edu
Preeclampsia is characterized by the development of proteinuria and hypertension after 20 weeks gestation, and it is associated with maternal and fetal morbidity. Preeclampsia affects ∼5% of pregnancies, though women with preexisting diabetes are three to four times more likely to develop preeclampsia (1). Preeclampsia is associated with altered angiogenic factors, including increased levels of circulating soluble FMS-like tyrosine kinase 1 (sFlt1) and reduced levels of vascular endothelial growth factor and placental growth factor (PlGF). Hypertension and proteinuria of preeclampsia may be caused by an imbalance of these angiogenic factors (2–10). Circulating sFlt1, an antiangiogenic protein, binds to proangiogenic proteins, vascular endothelial growth factor, and PlGF, preventing their interaction with endothelial cell receptors and inducing endothelial dysfunction. Rats given sFlt1 develop proteinuria, hypertension, and glomerular endotheliosis, which are hallmarks of preeclampsia (3). Alterations in sFlt1 and PlGF are observed several weeks before symptoms (2).
It is unknown whether alterations in sFlt1 and PlGF are present in women with diabetes who then develop preeclampsia or whether a different pathway is responsible. Ultimately, it would be helpful to have a way to diagnose and predict preeclampsia in women with pregestational diabetes, as they frequently have preexisting hypertension and/or proteinuria, which make it difficult to differentiate superimposed preeclampsia.
We evaluated a small group of women with diabetes and compared levels of sFlt1 and PlGF at delivery in both those who developed preeclampsia and those …
