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(Hypertension. 2004;43:988.)
© 2004 American Heart Association, Inc.

Scientific Contributions

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

From the Renal Unit, Massachusetts General Hospital, and Harvard Medical School (R.T, J.L.E., M.W., K.V.S.), Boston; Renal Unit, Beth Israel Deaconess Hospital and Harvard Medical School (W.P.M., V.P.S., S.A.K.), Boston; National Institute of Diabetes (R.J.L.), Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.

Correspondence to Ravi Thadhani, MD, MPH, Bullfinch 127, 55 Fruit Street, Massachusetts General Hospital, Boston, MA 02114. E-mail thadhani.r{at}mgh.harvard.edu

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 testing 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 PlGF 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.

Key Words: pregnancy • insulin resistance • preeclampsia • clinical trials

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