Facteurs anti-angiogéniques et prééclampsie au cours de la grossesse diabétique de type 1

Abstract

Aims/hypothesis

Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFβ1, confer high risk of preeclampsia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in preeclampsia.

Methods

Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term.

Results

Approximately 22 % of the diabetic women developed preeclampsia, primarily after their third trimester visit. In women with preeclampsia (diabetic preeclampsia, N = 26) vs those without hypertensive complications (diabetic normotensive, N = 95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of preeclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic preeclampsia vs type 1 diabetic normotensive women at the third trimester visit (P < 0.05) and the normal rise of PlGF during pregnancy was blunted (P < 0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r² = 42 %; P < 0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (P < 0.0001).

Conclusions/interpretation

Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of preeclampsia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-eclampsia and may contribute to the high incidence of preeclampsia in this patient group.