Central Obesity Increases the Risk of Gestational Diabetes Partially Through Increasing Insulin Resistance

Abstract

Objective: This study 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 mellitus (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, WC and hip circumference were measured at gestational weeks 10 to 13. In a nested case-control study within the cohort, 115 GDM cases and 230 controls had fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and adiponectin measurements at gestational weeks 16 to 19. Poisson and conditional logistic regression models were used, adjusting for established risk factors for GDM, including prepregnancy overweight or 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 risk increased 2.41-fold (95% CI: 1.14-5.06), and in those with established risk factors it increased 6.22-fold (95% CI: 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 9% to 11%; corresponding mediation proportions for the WC-GDM association were 35% to 41% (all P < 0.04).

Conclusions: Central obesity in early pregnancy represented a high-risk phenotype for GDM independent of other risk factors, including overweight or obesity, and may inform early screening and prevention strategies.

Fig. 1. Joint association of central obesity measures and established risk factors with risk of gestational diabetes

WC, waist circumference; WHR, waist-to-hip ratio. High-risk group was defined as women having one or more of the following established risk factors for gestational diabetes: age ≥35 years, high-risk race/ethnicity (Asian/Pacific Islander, African American, Hispanic, or other), prepregnancy overweight/obesity (BMI ≥23.0 or 25.0 kg/m² for Asians or non-Asians, respectively), family history of diabetes, previous gestational diabetes, and pre-existing hypertension. Low-risk group was defined as women having none of the above listed risk factors for gestational diabetes.

Fig. 2. Leave-one-out cross-validated incremental predictive value of waist-to-hip ratio (A) and waist circumference (B) in early pregnancy for subsequent risk of gestational diabetes

WC, waist circumference; WHR, waist-to-hip ratio. C statistics were estimated by leave-one-out cross validation for risk prediction of gestational diabetes using waist-to-hip ratio or waist circumference (red curve), in addition to the conventional model including established risk factors (age ≥35 years, high5risk race/ethnicity [Asian/Pacific Islander, African American, Hispanic, or other], prepregnancy overweight/obesity (BMI ≥23.0 or 25.0 kg/m² for Asians or non-Asians, respectively), family history of diabetes, previous gestational diabetes, and pre-existing hypertension; blue curve).