Obesity tied to gestational diabetes risk

Obesity appears to exert a detrimental causal effect on the risk of gestational diabetes (GDM), with lipid metabolism acting as a potential driver of the relationship, according to the results of a Mendelian randomization (MR) analysis.

Researchers drew summary-level data from the largest available genome-wide association studies of five obesity traits, five lipid traits, and GDM. They examined genetically predicted causal associations of general and central obesity with GDM, as well as explored the mediating role of circulating lipids.

Total effect was estimated using two-sample univariate MR, the direct effect using multivariate MR, and the mediating effect using MR-based mediation analysis.

Univariate MR showed that GDM both general and central obesity were associated with GDM. The odds of GDM rose per 1-SD increase in body mass index (BMI; odds ratio [OR], 1.64; p=5.05×10⁻¹⁷), in waist-to-hip ratio (WHR; OR, 1.57; p=2.27×10⁻¹⁴), and in WHR adjusted for BMI (OR, 1.42; p=6.11×10⁻¹⁵).

On further analysis, GDM also had heterogeneous associations with waist circumference (OR, 1.64; p=5.57×10⁻¹⁴) and hip circumference (OR, 1.20; p=0.002), suggesting that body fat distribution could influence GDM risk.

Finally, circulating triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I each mediated between 5 percent and 10 percent of the association between obesity and GDM.