Central obesity increases the risk of gestational diabetes partially through increasing insulin resistance

OBJECTIVE: We examined the associations of central obesity measures, waist-to-hip ratio (WHR) and waist circumference (WC), in early pregnancy with subsequent risk of gestational diabetes (GDM); and evaluated the potential mediating role of insulin resistance markers. METHODS: Within the prospective Pregnancy Environment and Lifestyle Study cohort of 1,750 women, waist and hip circumferences were measured at gestational weeks 10–13. In a nested case-control study within the cohort, 115 GDM cases and 230 controls had fasting serum insulin, HOMA-IR, and adiponectin measurements at gestational weeks 16–19. Poisson and conditional logistic regression models were used, adjusting for established risk factors for GDM including prepregnancy overweight/obesity. RESULTS: For women with WHR<0.85, one or more established risk factors increased GDM risk 1.99-fold (95% CI 0.99–4.02). For women with WHR≥0.85, but no established risk factors, GDM risks increased 2.41-fold (1.14–5.06), and with other risk factors, 6.22-fold (3.49–11.10). Similar but attenuated results were observed for WC≥88 cm. Insulin, HOMA-IR, and adiponectin levels mediated the WHR-GDM association by 9511%; corresponding mediation proportions for the WC-GDM association were 35–41% (all P-values<0.04). CONCLUSIONS: Central obesity in early pregnancy represented a high-risk phenotype for GDM independent of other risk factors including overweight/obesity and may inform early screening and prevention strategies.