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

Diabetologia. 2009 Jan;52(1):160-8. doi: 10.1007/s00125-008-1182-x. Epub 2008 Nov 5.

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 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/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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiogenesis Inhibitors / blood*
  • Antigens, CD / blood
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Endoglin
  • Eye Proteins / blood
  • Female
  • Glycated Hemoglobin A / analysis
  • Growth Hormone / blood
  • Humans
  • Membrane Proteins / blood
  • Nerve Growth Factors / blood
  • Pre-Eclampsia / blood*
  • Pregnancy
  • Pregnancy Complications / blood
  • Receptors, Cell Surface / blood
  • Serpins / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Angiogenesis Inhibitors
  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Eye Proteins
  • Glycated Hemoglobin A
  • Membrane Proteins
  • Nerve Growth Factors
  • PIGF protein, human
  • Receptors, Cell Surface
  • Serpins
  • pigment epithelium-derived factor
  • Growth Hormone
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1