title: Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women.
abstract: 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.
authors.affiliation: Harold Hamm Oklahoma Diabetes Center & Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: A J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: A J
authors.initials: AJ
authors.lastname: Nankervis
authors.forename: K F
authors.initials: KF
authors.lastname: Hanssen
authors.forename: H
authors.initials: H
authors.lastname: Scholz
authors.forename: T
authors.initials: T
authors.lastname: Henriksen
authors.forename: B
authors.initials: B
authors.lastname: Lorentzen
authors.forename: T
authors.initials: T
authors.lastname: Clausen
authors.forename: S K
authors.initials: SK
authors.lastname: Garg
authors.forename: M K
authors.initials: MK
authors.lastname: Menard
authors.forename: S M
authors.initials: SM
authors.lastname: Hammad
authors.forename: J C
authors.initials: JC
authors.lastname: Scardo
authors.forename: J R
authors.initials: JR
authors.lastname: Stanley
authors.forename: A
authors.initials: A
authors.lastname: Dashti
authors.forename: K
authors.initials: K
authors.lastname: May
authors.forename: K
authors.initials: K
authors.lastname: Lu
authors.forename: C E
authors.initials: CE
authors.lastname: Aston
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
authors.forename: S X
authors.initials: SX
authors.lastname: Zhang
authors.forename: J-X
authors.initials: JX
authors.lastname: Ma
authors.forename: T J
authors.initials: TJ
authors.lastname: Lyons
mesh_terms: 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
chemical_list: 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