Sex Hormone–Binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes—A Longitudinal Pregnancy Cohort Study and a Meta-analysis

Background: Sex hormone-binding globulin (SHBG) has been implicated in glucose metabolism and the development of type 2 diabetes. However, its role in glucose metabolism during pregnancy is unclear.

Objectives: This study investigated the prospective associations of SHBG with cardiometabolic biomarkers during pregnancy and gestational diabetes (GDM) risk.

Methods: We conducted a nested case-control study of 107 GDM cases and 214 matched controls without GDM in the NICHD Fetal Growth Studies-Singleton Cohort. GDM was ascertained by medical record review. Blood samples were drawn at 10-14, 15-26, 23-31 and 33-39 gestational weeks (GW). Prospective associations of SHBG with cardiometabolic biomarkers were estimated using Spearman’s correlation coefficient adjusting for potential confounders. Difference in SHBG levels between GDM and non-GDM women was estimated in the present study cohort and a meta-analysis of existing prospective evidence. Odds ratios (OR) for GDM by SHBG quartiles were estimated using conditional logistic regression.

Results: SHBG at GW 10-14 was significantly and inversely related to fasting glucose, fasting insulin, insulin resistance and HbA1c levels, and positively related to high-density lipoprotein and cholesterol levels at GW 15-26. Cases had lower SHBG levels compared to controls at GW 10-14 (mean ± SD: 204.0 ± 97.6 vs. 220.9 ± 102.5 nmol/L) and 15-26 (305.6 ± 124.3 vs. 322.7 ± 105.1 nmol/L), yet the differences were not significant. Meta-analysis of 11 prospective studies, including ours, estimated SHBG levels to be 0.50 SD (95% CI: 0.36-0.65) lower among women with than without GDM.

Conclusions: Higher SHBG levels in early pregnancy was associated with a favorable glucose metabolic profile among pregnant women. Synthesis of prospective studies supports an inverse association between SHBG levels and GDM risk.