Li Meng-Ying, Rawal Shristi, Hinkle Stefanie N, Zhu Ye-Yi, Tekola-Ayele Fasil, Tsai Michael Y, Liu Si-Min, Zhang Cui-Lin
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda MD 20817, USA.
Department of Nutritional Sciences, School of Health Professions, Rutgers University, Newark NJ 07107, USA.
Matern Fetal Med. 2020 Jan 24;2(1):2-9. doi: 10.1097/FM9.0000000000000037. eCollection 2020 Jan.
This study investigated the prospective associations of circulating levels of sex hormone-binding globulin (SHBG) levels with cardiometabolic biomarkers and risk of gestational diabetes (GDM) during pregnancy. It also examines the longitudinal trajectory of SHBG in women with and without GDM.
We conducted a nested case-control study of 107 incident GDM cases and 214 matched controls within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The cohort enrolled non-obese and obese women aged 18-40 years with a singleton pregnancy between 8 and 13 weeks of gestation from 2009 to 2013. GDM was ascertained via medical records review. Blood samples were drawn four times at gestational weeks 10-14, 15-26, 23-31, and 33-39. The prospective associations between SHBG levels and cardiometabolic biomarkers were examined using the Spearman partial correlation among the controls. The longitudinal trajectories of SHBG levels were examined among the cases and the controls. Meta-analysis of prospective studies were performed to examine the association between SHBG levels and GDM risk.
SHBG levels at gestational weeks 10-14 were significantly inversely associated with fasting insulin ( = -0.17, = 0.01) and insulin resistance as measured by HOMA-IR (= -0.17, = 0.01) at gestational week 15-26. SHBG at gestational weeks 10-14 and 15-26 was lower in cases than controls (mean ± standard deviation: (204.0 ± 97.6) . (220.9 ± 102.5) nmol/L, = 0.16 and (305.6 ± 124.3) . (322.7 ± 105.1) nmol/L, = 0.14, respectively), yet the differences were not significant. In the meta-analysis, SHBG was 41.5 nmol/L (95% confidence interval: 23.9, 59.1, < 0.01) significantly lower among women with GDM than without, and each 50 nmol/L increase in SHBG was significantly associated with an odds ratio of 0.85 (95% confidence interval: 0.76-0.95, = 0.01) for GDM.
Lower SHBG levels in early pregnancy were prospectively associated with higher high insulin levels and insulin resistance in mid-pregnancy and subsequent risk of GDM, independent of adiposity. SHBG may serve as a marker for the identification of high-risk pregnancies during early pregnancy.
本研究调查了孕期循环中性激素结合球蛋白（SHBG）水平与心血管代谢生物标志物及妊娠期糖尿病（GDM）风险之间的前瞻性关联。同时还研究了患有和未患有GDM的女性中SHBG的纵向变化轨迹。
我们在尤妮斯·肯尼迪·施莱佛国家儿童健康与人类发展研究所单胎队列胎儿生长研究中进行了一项巢式病例对照研究，纳入了107例新发GDM病例和214例匹配对照。该队列纳入了2009年至2013年期间年龄在18 - 40岁、单胎妊娠、妊娠8至13周的非肥胖和肥胖女性。通过病历审查确定GDM。在妊娠第10 - 14周、15 - 26周、23 - 31周和33 - 39周采集四次血样。使用对照组中的Spearman偏相关分析SHBG水平与心血管代谢生物标志物之间的前瞻性关联。在病例组和对照组中研究SHBG水平的纵向变化轨迹。进行前瞻性研究的荟萃分析以检验SHBG水平与GDM风险之间的关联。
妊娠第10 - 14周时SHBG水平与妊娠第15 - 26周时的空腹胰岛素（r = -0.17，P = 0.01）以及通过HOMA-IR测量的胰岛素抵抗（r = -0.17，P = 0.01）显著负相关。病例组妊娠第10 - 14周和15 - 26周时的SHBG低于对照组（均值±标准差：(204.0 ± 97.6) 对 (220.9 ± 102.5) nmol/L，P = 0.16；以及(305.6 ± 124.3) 对 (322.7 ± 105.1) nmol/L，P = 0.14），但差异不显著。在荟萃分析中，患有GDM的女性的SHBG显著低于未患GDM的女性，差值为41.5 nmol/L（95%置信区间：23.9，59.1，P < 0.01），并且SHBG每增加50 nmol/L，GDM的优势比显著降低至0.85（95%置信区间：0.76 - 0.95，P = 0.01）。
妊娠早期较低的SHBG水平与妊娠中期较高的高胰岛素水平和胰岛素抵抗以及随后的GDM风险前瞻性相关，且独立于肥胖因素。SHBG可作为孕早期识别高危妊娠的标志物。
