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

Abstract

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.

Retinol-binding protein 4 (RBP4) circulating levels and gestational diabetes mellitus: a systematic review and meta-analysis

“…The noted moderate effect size during this pregnancy period suggests that such elevated circulating RBP4 levels may be associated to GDM. This finding is in accord with previous research indicating the potential role of RBP4 in insulin resistance and glucose metabolism regulation after the first trimester of pregnancy ( 13 – 15 ). Thus, monitoring circulating RBP4 levels in pregnant women during the second trimester could be further explored as a potential GDM biomarker.…”

“…This finding suggests that circulating RBP4 levels in early pregnancy may be an early biomarker for GDM; although, the limited number of eligible existing studies for this early pregnancy timepoint warrants caution in interpreting this finding. Nevertheless, this is in accord to that from a previous meta-analysis from Wu et al ( 13 ) on the association between RBP4 levels in early pregnancy and GDM risk. However, the paucity of relevant data for this pregnancy trimester/timepoint was also noted in this previous meta-analysis, together with potential ethnic-related differences; hence, further research is clearly required to determine if circulating RBP4 has potential as a GDM-related biomarker during the first trimester.…”

“…Concerning handling incomplete outcome data, one study was at a high risk of bias, while one other had an unclear risk in this category; the remaining studies ( n = 32; 91%) were judged to have a low risk of bias. In the selective outcome reporting domain, all studies apart from one had a low risk of bias ( 13 , 18 – 25 , 28 , 31 – 33 , 35 , 39 – 57 ); Zhu et al ( 58 ) was judged to have an unclear risk.…”

“…From the nine studies that examined the relationship between circulating RBP4 levels during the first pregnancy trimester and GDM, seven were meta-analyzed ( 13 , 18 – 20 , 32 , 41 , 54 ) (946 GDM vs. 1701 non-GDM controls). Based on these, circulating RBP4 levels were statistically higher in pregnant women with GDM compared to pregnant controls (SMD: 0.322; 95% CI: 0.126 to 0.517; p < 0.001) ( Figure 3 ).…”

“…In this context, there has been increasing interest in investigating the potential role of RBP4 as a novel biomarker for GDM. However, the reported results have been inconsistent, with previous meta-analyses suggesting that serum RBP4 levels in early pregnancy show an independent positive association with GDM risk ( 13 ), and that Asian women with GDM had increased circulating RBP4 levels during the second/third pregnancy trimester ( 14 ). Although such data support the hypothesis that circulating RBP4 may be linked to GDM ( 15 ), there is still a need for a comprehensive systematic analysis and an updated meta-analysis of the relevant published studies examining the association between GDM and circulating RBP4 levels measured during all pregnancy stages/trimesters.…”