Wolf Myles, Sandler Laura, Muñoz Kristine, Hsu Karen, Ecker Jeffrey L, Thadhani Ravi
Renal Unit, Departments of Medicine and Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2002 Apr;87(4):1563-8. doi: 10.1210/jcem.87.4.8405.
Insulin resistance is implicated in the pathogenesis of preeclampsia, but prospective data are limited. SHBG, a marker of insulin resistance among nonpregnant individuals, has not been studied in detail during pregnancy. We conducted a prospective, nested, case-control study to test the hypothesis that increased insulin resistance, marked by reduced first trimester SHBG levels, is associated with increased risk of subsequent preeclampsia. First trimester SHBG levels were measured in 45 nulliparous women who subsequently developed preeclampsia (blood pressure, > or =140/90 mm Hg; proteinuria, either > or =2+ by dipstick or > or =300 mg/24 h, after 20 wk gestation) and in 90 randomly selected normotensive nulliparous controls. Compared with controls, women who developed preeclampsia had significantly reduced first trimester SHBG levels (302 +/- 130 vs. 396 +/- 186 nmol/liter; P < 0.01). Every 100 nmol/liter increase in SHBG was associated with a 31% reduced risk of preeclampsia [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.55, 0.88; P < 0.01]. After adjusting for covariates in a multiple logistic regression model, the association between first trimester SHBG and preeclampsia remained significant (per 100 nmol/liter increase; OR, 0.66; 95% CI, 0.47, 0.92; P = 0.01). When subjects were stratified by body mass index (lean: body mass index, < 25 kg/m(2); overweight: body mass index, > or =25 kg/m(2)), overweight women had lower SHBG levels than lean women (286 +/- 156 vs. 410 +/- 166 nmol/liter; P < 0.01), and within each stratum, women with preeclampsia had lower SHBG levels than their respective controls. In a multivariable analysis, the association between SHBG and preeclampsia strengthened among lean women, such that every 100 nmol/liter increase in serum SHBG was associated with a 55% reduction in the risk of preeclampsia (OR, 0.45; 95% CI, 0.27, 0.77; P < 0.01), whereas in overweight women, the association was mitigated (OR, 1.02; 95% CI, 0.62, 1.69; P = 0.9). We conclude that increased early pregnancy insulin resistance is independently associated with subsequent preeclampsia. First trimester SHBG levels may be a useful biomarker for preeclampsia, especially among lean women who otherwise would be perceived to be at low risk.
胰岛素抵抗与先兆子痫的发病机制有关，但前瞻性数据有限。性激素结合球蛋白（SHBG）是未孕个体胰岛素抵抗的一个标志物，在孕期尚未进行详细研究。我们开展了一项前瞻性巢式病例对照研究，以检验以下假设：孕早期SHBG水平降低所标志的胰岛素抵抗增加与随后发生先兆子痫的风险增加相关。对45例初产妇进行了孕早期SHBG水平测定，这些产妇随后发生了先兆子痫（血压≥140/90 mmHg；蛋白尿，妊娠20周后试纸检测≥2+或24小时尿蛋白≥300 mg），并与90例随机选择的血压正常的初产妇对照。与对照组相比，发生先兆子痫的女性孕早期SHBG水平显著降低（302±130 vs. 396±186 nmol/L；P<0.01）。SHBG每增加100 nmol/L，先兆子痫风险降低31%[比值比（OR），0.69；95%置信区间（CI），0.55，0.88；P<0.01]。在多因素逻辑回归模型中对协变量进行校正后，孕早期SHBG与先兆子痫之间的关联仍然显著（每增加100 nmol/L；OR，0.66；95%CI，0.47，0.92；P = 0.01）。当根据体重指数对受试者进行分层时（瘦：体重指数<25 kg/m²；超重：体重指数≥25 kg/m²），超重女性的SHBG水平低于瘦女性（286±156 vs. 410±166 nmol/L；P<0.01），并且在每个分层中，发生先兆子痫的女性的SHBG水平低于各自的对照组。在多变量分析中，SHBG与先兆子痫之间的关联在瘦女性中增强，血清SHBG每增加100 nmol/L，先兆子痫风险降低55%（OR，0.45；95%CI，0.27，0.77；P<0.01），而在超重女性中，这种关联减弱（OR，1.02；95%CI，0.62，1.69；P = 0.9）。我们得出结论，孕早期胰岛素抵抗增加与随后发生先兆子痫独立相关。孕早期SHBG水平可能是先兆子痫的一个有用生物标志物，尤其是在那些原本被认为风险较低的瘦女性中。
