Introduction
The low-density lipoprotein receptor-related protein 5 (LRP5) and its inhibitor sclerostin, are key components of bone metabolism and potential contributors to type 2 diabetes mellitus susceptibility. This study aims at evaluating the expression of placental LRP5 and sclerostin in pregnancies with gestational diabetes mellitus (GDM) and investigate possible associations with umbilical sclerostin concentrations and clinical outcomes in mothers and their neonates.
Methods
Twenty-six GDM-mothers and 34 non-GDM mothers of Caucasian origin and their neonates admitted in a Gynecology and Obstetrics Department of a university hospital were included in this study. Demographic data and maternal fasting glucose concentrations (24-28 weeks of gestation) were retrieved from the patients’ medical records. Placental LRP5 was determined by immunohistochemistry (IHC) and Western blotting (WB) analysis, while placental sclerostin by IHC. Umbilical serum sclerostin concentrations were measured by ELISA.
Results
Placental sclerostin IHC intensity values were positively correlated with LRP5 values as detected either by IHC (r=0.529; p<0.001) or WB (r=0.398; p=0.008), with pregestational maternal BMI values (r=0.299; p=0.043) and with maternal fasting glucose concentrations (r=0.475; p=0.009). Placental sclerostin and LRP5 were significantly greater in GDM compared to non-GDM placentas (h-score: 65.08±17.09 vs. 11.45±2.33, p<0.001; 145.53±43.74 vs. 202.88±58.65, p<0.001; respectively).
Discussion
Sclerostin and LRP5 were detected in human placentas. The overexpression of placental sclerostin and LRP5 values in GDM compared to non-GDM pregnancies, as well as the positive association of placental sclerostin values with pregestational maternal BMI and maternal fasting glucose concentrations may indicate the development of an adaptive mechanism in face of maternal hyperglycemia.
BACKGROUND:
Offspring exposed in foetal life to gestational diabetes mellitus (GDM) are at increased risk for future metabolic diseases.
OBJECTIVE:
To explore the prognostic role of abdominal aorta intima-media thickness (aIMT) in neonates exposed to GDM as a possible biomarker for later atherogenesis and its possible correlation with thioredoxin-interacting protein (TXNIP), a protein involved in oxidative stress.
METHODS:
In this prospective, observational study, mother-infant pairs were studied in 2 groups (57 patients with GDM and 51 controls without GDM). TXNIP levels were measured in the placenta, as well as in the umbilical and neonatal blood. The data were correlated with aIMT in neonates.
RESULTS:
aIMT was increased in GDM offspring (patients: median [range]=0.39 mm [0.31-0.46] vs controls: median=0.28 mm [0.23-0.33]; p=0.001) and remained significant after adjusting for possible confounders (e.g., triglycerides, blood pressure, vitamin D, birth weight and gender; β coefficient=0.131 p=0.049). TXNIP levels were increased in trophoblasts (p=0.001) and syncytiotrophoblasts (p=0.001) and were decreased in endothelial cells (p=0.022) in GDM offspring vs controls. Moreover, TXNIP levels in trophoblasts positively correlated with aIMT (r=0.369; p=0.001). TXNIP levels in umbilical/neonatal blood were not associated with GDM.
CONCLUSIONS:
Increased aIMT was demonstrated in the offspring of mothers with GDM. Non-invasive measurement of aIMT could be used as a biomarker to identify children at increased risk for atherogenesis later in life. This information may encourage early preventive measures. TXNIP may be associated with GDM and/or aIMT.
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