Abstract
ContextThe Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth.ObjectiveTo analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity.Design and methodsA prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity.ResultsSerum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (β = −0.199, P = 0.008) and the diagnosis of gestational diabetes (β = −0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (β = 0.214, P = 0.005 and β = 0.231, P = 0.002, respectively).ConclusionsCirculating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin-Follistatin system in maternal and fetal metabolism during pregnancy.
Highlights
Gestational diabetes mellitus (GDM) is one of the most frequent metabolic disorders complicating pregnancy
Serum follistatin levels were significantly lower in GDM than in normal glucose tolerance (NGT) pregnant women (8.2162.32 ng/mL vs 9.2263.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups
In the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with Homeostasis model of insulin resistance (HOMA-IR) (b = 20.199, P = 0.008) and the diagnosis of gestational diabetes (b = 20.138, P = 0.049)
Summary
Gestational diabetes mellitus (GDM) is one of the most frequent metabolic disorders complicating pregnancy. Late pregnancy is a state of physiological insulin resistance in which nutritional, hormonal and inflammatory factors are involved. When pregnant women fail to overcome this insulin resistance, GDM develops [1]. This metabolic disturbance modifies the in utero environment affecting fetal development and favoring fetal overgrowth and adipose tissue accretion. It has been shown that the measurement of fractional limb volume, a soft tissue parameter of fetal body composition, is more accurate to monitor fetal nutritional status and is closely related to neonatal adiposity [4]
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