Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women.
OBJECTIVE
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 TGFbeta1, 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
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.
Yu
Y
Y
Harold Hamm Oklahoma Diabetes Center & Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jenkins
A J
AJ
Nankervis
A J
AJ
Hanssen
K F
KF
Scholz
H
H
Henriksen
T
T
Lorentzen
B
B
Clausen
T
T
Garg
S K
SK
Menard
M K
MK
Hammad
S M
SM
Scardo
J C
JC
Stanley
J R
JR
Dashti
A
A
May
K
K
Lu
K
K
Aston
C E
CE
Wang
J J
JJ
Zhang
S X
SX
Ma
J-X
JX
Lyons
T J
TJ
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000097:blood*; D015703:Antigens, CD / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D000071063:Endoglin; D005136:Eye Proteins / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood; D015843:Serpins / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D000071063:Endoglin; D005136:Eye Proteins; D006442:Glycated Hemoglobin; D013006:Growth Hormone; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D015843:Serpins; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099174:Pigment Epithelium-Derived Factor; C064206:ENG protein, human; C098069:PIGF protein, human; C501162:FLT1 protein, human