Insulin Resistance and Alterations in Angiogenesis: Additive Insults That May Lead to Preeclampsia

Ravi Thadhani*, Jeffrey L. Ecker, Walter P. Mutter, Myles Wolf, Karen V. Smirnakis, Vikas P. Sukhatme, Richard J. Levine, S. Ananth Karumanchi

*Corresponding author for this work

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208±116 versus 256±101 nmol/L, P=0.05) and PlGF (16±14 versus 67±150 pg/mL, P<0.001), and in multivariable analysis, women with serum levels of PlGF ≤20 pg/mL had an increased risk of developing preeclampsia (odds ratio [OR] 7.6, 95% CI 1.4 to 38.4). Stratified by levels of serum SHBG (≤175 versus >175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal tesfing for interaction (PlGFXSHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PIGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia.

Original languageEnglish (US)
Pages (from-to)988-992
Number of pages5
JournalHypertension
Volume43
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Clinical trials
  • Insulin resistance
  • Preeclampsia
  • Pregnancy

ASJC Scopus subject areas

  • Internal Medicine

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    Thadhani, R., Ecker, J. L., Mutter, W. P., Wolf, M., Smirnakis, K. V., Sukhatme, V. P., Levine, R. J., & Karumanchi, S. A. (2004). Insulin Resistance and Alterations in Angiogenesis: Additive Insults That May Lead to Preeclampsia. Hypertension, 43(5), 988-992. https://doi.org/10.1161/01.HYP.0000124460.67539.1d