Angiogenic Imbalance and Inflammatory Biomarkers in the Prediction of Hypertension as Well as Obstetric and Perinatal Complications in Women with Gestational Diabetes Mellitus.

Almudena Lara-Barea,Fernando Bugatto,Cristina López-Tinoco,Manuel Aguilar-Diosdado,Juan Antonio Córdoba-Doña,Raquel De La Varga-Martínez,Begoña Sánchez-Lechuga,Antonio Campos-Caro,Ana I Arroba

doi:10.3390/jcm11061514

Abstract

Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28–32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23–0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24–5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

Highlights

Hypertensive disorders of pregnancy (HDP) are present in 5–10% of gestations worldwide and contribute to an increase in maternal and neonatal complications [1]
One hypothesis claims that the association between gestational diabetes mellitus (GDM) and preeclampsia could be—at least partly—due to insulin resistance and its adaptation in normal pregnancy, whereas in individuals predisposed to other risk factors this could lead to pathological processes, such as the development of GDM and preeclampsia [5,6]
Our results revealed no differences in both of these biomarkers in pregnancies complicated by intrauterine growth restriction (IUGR) among women who developed HDP, but we did find that the soluble fms-like tyrosine kinase-1 (sFlt-1)/PIGF ratio was negatively correlated with the week of pregnancy at delivery and the weight of the newborn in women with GDM who developed subsequent HDP, both of which were consistent with those reported by other authors [47,48]

Summary

Introduction

Hypertensive disorders of pregnancy (HDP) are present in 5–10% of gestations worldwide and contribute to an increase in maternal and neonatal complications [1]. In pregnant women with pregestational diabetes, the risk is around 20%, compared to women without diabetes where it is around 5% [2]. Pregnant women with gestational diabetes mellitus (GDM) have an increased risk of HDP compared with non-GDM women [3], the rate is variable due to the low disease prevalence of both conditions, the lack of a universal disease classification, and interdependent risk factors for both GDM and HDP [4]. One hypothesis claims that the association between GDM and preeclampsia could be—at least partly—due to insulin resistance and its adaptation in normal pregnancy, whereas in individuals predisposed to other risk factors this could lead to pathological processes, such as the development of GDM and preeclampsia [5,6]. Prospective studies illustrate the link between the downregulation of adiponectin as well as anti-inflammatory cytokines (e.g., IL-4 and IL-10) and the upregulation of leptin as well as proinflammatory cytokines implicated in insulin resistance (e.g., IL-6 and TNF-α) [7,8]

Objectives

Methods

Results

Conclusion