Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women |
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Authors: | 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 |
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Institution: | Harold Hamm Oklahoma Diabetes Center & Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. |
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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 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 (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 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. |
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Keywords: | Anti-angiogenic factors Diabetes Endoglin Pigment epithelium-derived factor Placental growth factor Pre-eclampsia Pregnancy sFlt1 Soluble VEGF receptors |
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