Central obesity has been linked to type 2 diabetes but prospective data are limited among pregnant women. We examined the associations of central obesity measures, waist-to-hip ratio (WHR) and waist circumference (WC), in early pregnancy with subsequent gestational diabetes (GDM) risk; and evaluated the potential for insulin resistance markers to mediate the central obesity and GDM association. Within the Pregnancy Environment and Lifestyle Study prospective cohort of 1,750 women, waist and hip circumferences were measured at 10-13 weeks of gestation. In a nested case-control study within the cohort, 115 GDM cases ascertained by Carpenter-Coustan criteria and 230 non-GDM controls had fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and adiponectin measurements at weeks 16-19. Multivariable Poisson and conditional logistic regression models were used, adjusting for established risk factors including age ≥35 years, minority race/ethnicity, pre-pregnancy overweight/obesity, family history of diabetes, previous GDM, and preexisting hypertension. Compared to women with WHR <0.85 and no established risk factors, women with WHR ≥0.85 and no risk factors had a 3.74-fold (95% CI 1.92-7.27) increased risk of GDM, and women with WHR ≥0.85 and at least one risk factor had a 6.63-fold (3.48-12.63) increased risk. In the receiver-operating-characteristic curve analysis, WHR significantly improved GDM risk prediction beyond established risk factors (C-statistics 0.796 vs. 0.744, P-for-difference <0.0001). Similar but attenuated results were observed for WC ≥88cm. Insulin, HOMA-IR, and adiponectin levels mediated the WHR-GDM association by 9.0%, 9.6%, and 11.1%, respectively; corresponding mediation proportions for WC-GDM were 40.0%, 41.1%, and 35.4% (all P-values <0.04). Our findings suggest that central obesity in early pregnancy represented a high-risk phenotype for GDM and may help identify at-risk women for early screening, prevention, and treatment.
Y. Zhu: None. M. Hedderson: None. C. Quesenberry: None. J. Feng: None. A. Ferrara: None.