A Prospective Study of Maternal Plasma Concentrations of Retinol-Binding Protein 4 and Risk of Gestational Diabetes Mellitus

Abstract

Background: The aim of this study was to investigate whether retinol-binding protein 4 (RBP4) concentrations, measured at the first prenatal visit, are associated with risk of gestational diabetes mellitus (GDM). Methods: From July 2015 to June 2016, consecutive women who admitted to the obstetrics center of our hospital were included. At the first prenatal visit (the median gestational age was 6 [interquartile range 4–10] weeks) in the hospital, involved subjects were tested for fasting plasma glucose (FPG) and RBP4 using venous plasma samples collected after at least 8 h of fasting in the morning. Data for FPG and RBP4 concentrations at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test performed between 24 and 28 weeks of gestation were collected and analyzed. Results: Blood at first prenatal visit was available for 827 women, among whom GDM developed in 101 (12.2%). In multivariate models comparing the second (Q2), third, and fourth quartiles against the first quartile of RBP4, concentrations of RBP4 in Q2, Q3, and Q4 were associated with GDM later developed, and increased risk of GDM by 54, 205, and 536%. There was a significant statistical difference in the area under the curve between the established risk factors alone and the addition of RBP4 concentrations (difference, 0.039 [95% CI 0.030–0.052]; p = 0.03). In the subgroup of women combined with obesity and FABP4 ≥median, the measured OR was 9.83 (95% CI [4.76–16.13]; p < 0.001) for GDM compared to those without obesity and FABP4 <median. Conclusions: There is evidence of a positive association of early pregnancy elevated RBP4 concentration with increased GDM risk, particularly among women with advanced age and obesity.

Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases

“…Interestingly, high levels of FABP4 were proposed as a predictive biomarker of GDM from at the 1st and 3rd trimester of gestation [133–135]. Also, an upregulation of plasma RBP4 at the 1st and 2nd trimester was modestly correlated with GDM risk, particularly among women with advanced age and obesity [115, 136] (Table 3A). Finally, fibroblast growth factor-23 (FGF-23) is as a multi-functional cytokine with relevant implications in phosphate and vitamin-D metabolism.…”

Vitamin A Requirements in Pregnancy and Lactation

“…Among diabetic pregnancies, the adipokine RBP does not have a statistically significant association with the occurrence of PE ( 92 ). Other studies have investigated the association between higher RBP concentrations and the risk of gestational diabetes, finding both positive ( 93–96 ) and negative associations ( 97 ).…”

Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study

“…The relationship between RBP4 levels in early pregnancy and the risk of GDM have been assessed by limited studies and inconclusive results were yielded. A prospective study found that compared with the first quartile of RBP4 in the first trimester, adjusted ORs of GDM for the second, third and fourth quartile were 1.54, 3.05 and 6.36 respectively [7]. Another case-control study found participants in the highest quartile of serum RBP4 had a 1.89 times higher risk of GDM compared with participants in the lowest quartile, while the relationship did not reach statistical significance after adjustment for maternal age, race, family history of diabetes, and pre-pregnancy overweight status [21].…”

“…Nevertheless, this metaanalysis only includes one article in the "before 24 weeks" subgroup and no association between serum RBP4 level and GDM risk was found [9]. Recently, a prospective study revealed that early pregnancy RBP4 concentrations were associated with increased risk of GDM [7]. However, none of the previous studies analyzed RBP4 levels at different trimesters before the diagnosis of GDM.…”

“…Several previous studies assessed the association between RBP4 and GDM and yielded inconsistent results [7,8]. A meta-analysis pooled results from 14 casecontrol studies reported that the serum RBP4 level was associated with the risk of GDM (pooled standardized mean difference = 0.816) [8].…”