Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia.
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 < or =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 (< or =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.
Thadhani
Ravi
R
Renal Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA. thadhani.r@mgh.harvard.edu
Ecker
Jeffrey L
JL
Mutter
Walter P
WP
Wolf
Myles
M
Smirnakis
Karen V
KV
Sukhatme
Vikas P
VP
Levine
Richard J
RJ
Karumanchi
S Ananth
SA
D015415:Biomarkers; D001724:Birth Weight; D001794:Blood Pressure; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007333:Insulin Resistance; D018919:Neovascularization, Physiologic; D010298:Parity; D010920:Placenta / Q000098:blood supply*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D016037:Single-Blind Method
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012738:Sex Hormone-Binding Globulin; D000072483:Placenta Growth Factor