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

Y. Yu, A.J. Jenkins, A.J. Nankervis, K.F. Hanssen, H. Scholz, T. Henriksen, B. Lorentzen, T. Clausen, S.K. Garg, M.K. Menard, S.M. Hammad, J.C. Scardo, J.R. Stanley, A. Dashti, K. May, K. Lu, C.E. Aston, J.J. Wang, S.X. Zhang, J.-X. MaT.J. Lyons

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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 TGFß1, 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.
Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalDiabetologia
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

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

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    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., ... Lyons, T. J. (2009). Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women. Diabetologia, 52(1), 160-168. https://doi.org/10.1007/s00125-008-1182-x