Association of Circulating GDF-15 with Fetal Growth in Gestational Diabetes

Background/Objectives: Growth differentiation factor-15 (GDF-15) is a component of the transforming growth factor beta (TGF-β) family that may act as regulator of inflammation. A possible protective role of GDF-15 against glucose alterations has been hypothesized. The aim of this pilot study was to evaluate the relationship between a circulating concentration of GDF-15 and metabolic/inflammatory parameters, as well as with adverse perinatal outcomes in patients with gestational diabetes mellitus (GDM). Methods: Twenty-four (n = 24) patients with GDM and n = 29 age-matched pregnant women with normal glucose tolerance (NGT) were recruited at the third trimester of gestation. Clinical and biochemical parameters were collected. Serum levels of GDF-15, small dense low density lipoprotein cholesterol (sdLDL), interleukin 6 (IL-6), a Soluble Urokinase Plasminogen Activator Receptor (su-PAR) were measured by an enzyme-linked immunosorbent assay kit. Fetal ultrasound parameters, maternal, delivery, and perinatal outcomes, were assessed. Results: Serum GDF-15 did not differ between GDM and NGT (p = 0.286). However, in linear regression analysis, a significant negative association was observed between GDF-15 and fetal weight percentile at the third trimester, only in patients with GDM (p = 0.013), even after adjustment for age and pre-pregnancy BMI (p = 0.029). GDF-15 positively associated with IL-6, adjusting for pre-pregnancy BMI (p = 0.047). Pregnant women with adverse perinatal outcomes had higher levels of GDF-15 (p = 0.043). In the regression model, higher levels of GDF-15 were associated with an increased likelihood of adverse perinatal outcomes after adjustment for age and pre-pregnancy BMI (p = 0.044). Conclusions: Besides its action as regulator of inflammation, GDF-15 might have a possible protective role against hyperglycemia-related excessive fetal growth in GDM. GDF-15 circulating levels might also be related to adverse perinatal outcomes.