Retinol-binding protein 4: a novel adipokine implicated in the genesis of LGA in the absence of gestational diabetes mellitus

Abstract

Objective: Adipokines (cytokines produced by adipose tissue) play a major role in the control of body weight and energy distribution. Retinol-binding protein 4 (RBP4), only recently recognized as an adipokine, has been proposed to modulate systemic insulin sensitivity. The goal of this study was to determine whether there is an association between maternal plasma RBP4 concentration and the birth of a large-for-gestational-age (LGA) newborn in women with and without gestational diabetes mellitus (GDM).

Study design: This cross-sectional study included pregnant women at term in the following groups: 1) normal pregnancy with an appropriate-for-gestational-age (AGA) neonate (n=64); 2) normal pregnancy with an LGA neonate (n=44); 3) GDM with an AGA neonate (n=55); and 4) GDM with an LGA neonate (n=42). Maternal plasma RBP4 concentration was determined by ELISA. Parametric and non-parametric statistics were used for analyses.

Results: 1) Patients with GDM, either with AGA or LGA neonates, had a higher median plasma concentration of RBP4 than normal pregnant women who delivered an AGA neonate (P=0.01 and P=0.008, respectively); 2) mothers without GDM but with LGA neonates had a higher median plasma concentration of RBP4 than those with normal pregnancy and AGA newborns (P=0.001); 3) these findings remained significant after adjusting for maternal age, body mass index and gestational age at blood sampling.

Conclusion: GDM is characterized by alterations in maternal circulating RBP4 concentrations akin to those of Type 2 diabetes mellitus. RBP4 concentrations in maternal plasma may play a role in accelerated fetal growth in the absence of overt carbohydrate intolerance.

Figure 1. Box and whisker plot of the comparison of the median maternal plasma RBP4 concentrations between women with and without GDM and/or an LGA fetus

The median maternal plasma RBP4 concentration was higher in patients with GDM, either with an AGA or with an LGA neonate, than in those with a normal pregnancy and an AGA fetus. Similarly, pregnant women with a normal pregnancy and an LGA neonate had a higher median maternal plasma RBP4 concentration than those with a normal pregnancy and an AGA newborn.

Figure 2. Box and whisker plot of the comparison of the median maternal plasma RBP4 concentrations between normal weight and overweight/obese pregnant women, with and without GDM and/or an LGA fetus

Among overweight/obese patients, the median maternal plasma RBP4 concentration was significantly higher in patients with GDM, either with an AGA or with LGA neonate, than in those with a normal pregnancy and an AGA neonate. Similarly, overweight/obese pregnant women with a normal pregnancy and an LGA newborn had a higher median maternal plasma RBP4 concentration than those with a normal pregnancy and an AGA neonate. In contrast, among normal weight pregnant women, there was no significant difference in the median maternal plasma RBP4 concentration between the different study groups. Within each study group, the median maternal plasma RBP4 concentration did not differ significantly between normal weight and overweight/obese pregnant women.