SAT-LB045 Maternal Obesity in Early Pregnancy Is Associated with the Decreased Active IGF-I Availability and Increased Leptin Concentrations

Abstract

Introduction: Maternal obesity (MO) is the global health problem, associated with high fetal and maternal mortality. Cardiovascular remodelling in obese pregnant patients has been linked to development of preeclampsia. IGF-I is important for maternal adaptation to pregnancy, e.g. maternal tissue growth and metabolism. Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5 releasing active IGF-I. Leptin, produced by placenta and adipose tissue, is a cytokine with cardio metabolic properties, the concentration of which is increased in obese subjects and in pregnant patients. The aim of this study was to evaluate serum levels of PAPP-A2 (as an indicator of IGF -I pathway activation) and Leptin in the obese and non-obese patients in first trimester of pregnancy. Glycosylated fibronectin (GlyFib) and Inhibin A (Inh A) were evaluated as additional a markers of remodelling and placental function (respectively). Material and methods. This was a prospective observational study, patients were enrolled during first trimester of pregnancy according to the IRB-approved protocol (L#17-136): obese (OB, BMI ≥ 30 kg/m2, n=13) and non-obese (nOB, BMI<30 kg/m2 , n=14). Patients with pre-pregnancy cardiovascular pathology were excluded. Concentrations of PAAP-A2, GlyFib, Inh A and Leptin were measured, using commercially available ELISAs: AL-109, AL-123 and AL-160 from AnshLab (Webster, TX, USA) and Invitrogen (Waltham, MA). The data are presented as Mean ± SEM. Results. In 3/13 OB and in 1/14 nOB patients PAAP-A2 concentrations were below 0.3 MoM (CI [4.8 - 34 ng/ml] and [CI 5.8-21 ng/ml] respectively). GlyFib (OB, 303.4 ± 35.6 µg/ml; nOB, 208.7 ± 19.26 µg/ml) and Leptin concentrations (OB, 72775 ± 3802 pg/ml; nOB, 48882 ± 4052 pg/ml) were increased in OB patients compared to nOB (*p<0.05; ***p<0.0005, Mann-Whitney test, respectively). Inh A concentrations (OB, 479.6 ± 105.9 pg/ml; nOB, 381 ± 81.65 pg/ml) did not differ between two groups. In the nOB population, incidence of preeclampsia was 1/15 (6.7%) which was not associated with low PAPP-A2 levels. In the OB population, incidence of preeclampsia was 3/10 (30%) where 2/3 of cases were associated with low PAPP-A2 levels. Discussion. IGF-I and Leptin regulate cardiovascular remodelling and placentation. The mismatch of these two factors might represent the mechanism of pathological cardiovascular adaptation in OB pregnant patients. Limitations of this study are small sample size, non-inclusion of other predisposed populations (PCOS, GDM, autoimmune disorders) and loss to follow-up. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.