Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women

作者：Yu Y; Jenkins A J; Nankervis A J; Hanssen K F; Scholz H; Henriksen T; Lorentzen B; Clausen T; Garg S K; Menard M K; Hammad S M; Scardo J C; Stanley J R; Dashti A; May K; Lu K; Aston C E; Wang J J; Zhang S X; Ma J X; Lyons T J^*

来源：Diabetologia, 2009, 52(1): 160-168.

DOI：10.1007/s00125-008-1182-x

• Anti-angiogenic factors
• Diabetes
• Endoglin
• Pigment epithelium-derived factor
• Placental growth factor
• Pre-eclampsia
• Pregnancy
• sFlt1
• Soluble VEGF receptors

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 TGF beta 1, confer high risk of pre-eclampsia 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 pre-eclampsia.
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 pre-eclampsia, primarily after their third trimester visit. In women with pre-eclampsia (diabetic pre-eclampsia, 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 pre-eclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-eclampsia 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 (r(2)=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 pre-eclampsia 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 pre-eclampsia in this patient group.

• 出版日期2009-1