Serum retinol-binding protein 4 levels and risk of gestational diabetes mellitus: A nested case-control study in Chinese women and an updated meta-analysis

Aims We prospectively evaluated the association of circulating retinol-binding protein 4 (RBP4) levels in early pregnancy and risk of incident gestational diabetes mellitus (GDM) in pregnant women. Methods A nested case-control study was conducted among 332 women who developed GDM and 664 matched controls based on the Tongji-Shuangliu Birth Cohort. GDM was diagnosed during 24-28 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group criteria. Serum RBP4 levels in early pregnancy (6-15 weeks of gestation) were determined by ELISA assay. Multivariable conditional logistic regression models were used to analyse the association and generated the odds ratio (OR) and 95% confidence interval (CI). EMBASE and PubMed were searched up to 30 November 2020 to identify studies investigating the association between blood RBP4 levels in early pregnancy and incident GDM. Results In the multivariable model with adjustment of potential risk factors, the OR comparing the extreme quartiles of serum RBP4 levels was 2.26 (95% CI: 1.34, 3.81; p for trend <0.001), and each standard deviation (SD) increment of RBP4 was associated with 1.39-fold (95% CI: 1.15, 1.69) higher risk of GDM. The results were confirmed in a meta-analysis that included additional four studies with an overall OR of 1.47 (95% CI: 1.18, 1.83) per 1-SD increment of RBP4. Conclusions Serum RBP4 levels in early pregnancy, independent of metabolic risk factors, are positively associated with the risk of GDM in pregnant women. Our findings may provide new insights into the mechanisms underlying the aetiology of GDM.