Changes in circulating levels of carboxymethyllysine, soluble receptor for advanced glycation end products (sRAGE), and inflammation markers in women during normal pregnancy

Objective: To determine the circulating levels of insulin, Nε-carboxymethyllysine (CML), soluble receptor for advanced glycation end products (sRAGE), and markers of inflammation and oxidative stress (OS) in maternal and umbilical cord blood in a cohort of healthy women with normal pregnancy. Methods: We conducted an observational longitudinal study in a group of women (n = 31; age range 18–39 years) with healthy pregnancy starting at 30 weeks of gestation and finishing at the time of delivery. We collected weight and height in the participants and their neonates and calculated body mass index (BMI). Blood from each patient was collected at 30th week of pregnancy and at delivery when a sample of cord blood was also obtained. Glucose, lipid profile, CML, sRAGE, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), highly sensitivity C-reactive protein (hsPCR), and insulin were determined. The study was approved by the University of Guanajuato Institutional Ethics Committee. Results: All pregnancies reached term (mean gestational time 38.9 ± 0.83 weeks) and there were no maternal complications. Mean age was 27.6 years. Lipid profile values were higher in the group compared with our values in nonpregnant women. During pregnancy, levels of insulin increased (p <.0006), CML (p <.0001) and sRAGE (p <.01) decreased, levels of MDA did not change, while those of TNF-α and hsPCR tended to increase. In the neonates, we found lower levels of CML (p <.003), hsPCR (p <.004), and insulin (p <.004) and higher levels of sRAGE (p <.013) and TNF-α (p <.022) compared to their mothers at delivery. In the total group, we found association of CML of the mother at baseline with the CML (p <.0006) and MDA (p <.002) in neonates, while maternal sRAGE at the end of pregnancy was associated with CML (p <.004) of their neonates. Conclusions: Our study confirms that normal pregnancy is accompanied by insulin resistance (IR) and significant increase in lipid profile, and demonstrates that circulating levels of CML and sRAGE decreased significantly at the end of pregnancy. The lack of association between the course of insulin levels and those of CML probably results from the predominant role of placental factors in the pathogenesis of IR in pregnancy. sRAGE levels in the neonates are markedly increased compared to their mothers suggesting a placental origin of this compound which may have a protective effect on the fetus since sRAGE restricts Advanced glycation end product (AGE) effects and may exert anti-inflammatory effects.