High Plasmatic Levels of Advanced Glycation End Products are Associated with Metabolic Alterations and Insulin Resistance in Preeclamptic Women

Abstract

Aims: The purpose of this study was to investigate the association between plasmatic levels of advanced end glycation products (AGEs) and the metabolic profile in subjects diagnosed with preeclampsia, due to the known relation of these molecules with oxidative stress and inflammation, which in turn are related with PE pathogenesis. Background: It has been reported that increased levels of AGEs are observed in patients with preeclampsia as compared with healthy pregnant subjects, which was mainly associated with oxidative stress and inflammation. Besides, in women with preeclampsia, there are metabolic changes such as hyperinsulinemia, glucose intolerance, dyslipidemia, among others, that are associated with an exacerbated insulin resistance. Additionally, some parameters indicate the alteration of hepatic function, such as increased levels of liver enzymes. However, the relationship of levels of AGEs with altered lipidic, hepatic and glucose metabolism parameters in preeclampsia has not been evaluated. Objective: To investigate the association between plasmatic levels of AGEs and hepatic, lipid and metabolic profiles in women diagnosed with preeclampsia. Methods: Plasma levels of AGEs were determined by a competitive enzyme-linked immunosorbent assay (ELISA) in 15 patients diagnosed with preeclampsia and 28 normoevolutive pregnant subjects (control group). Hepatic (serum creatinine, gamma-glutamyl transpeptidase, aspartate transaminase, alanine transaminase, uric acid, and lactate dehydrogenase), lipid (apolipoprotein A, apolipoprotein B, total cholesterol, triglycerides, low-density lipoproteins, and high-density lipoproteins) and metabolic variables (glucose, insulin, and insulin resistance) were assessed. Results: Plasmatic levels of AGEs were significantly higher in patients with preeclampsia as compared with the control. A positive correlation between circulating levels of AGEs and gamma-glutamyl transpeptidase, uric acid, glucose, insulin, and HOMA-IR levels was found in patients with preeclampsia. In conclusion, circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, variables of hepatic and metabolic profile, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance. Conclusions: Circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, hepatic and metabolic profiles, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance, suggesting that excessive glycation and an impaired metabolic profile contribute to the physiopathology of preeclampsia.

Could AGEs be markers of pre-eclampsia? Study of concentration of advanced protein glycation products in pregnant women with physiological pregnancy and pregnancy complicated with pre-eclampsia

“…Little is known about the levels of circulating AGEs in pregnancy. One study found elevated serum AGE levels in women with PE [17], while another suggested that gestational diabetes was associated with increased serum AGE levels [18]. Single studies indicate the potential applicability of protein glycation end products in predicting premature rupture of the amniotic fluid sac and preterm labor [19].…”

Maternal Tryptophan Catabolites and Insulin Resistance Parameters in Preeclampsia

“…Mid-trimester maternal IR is associated with later PE [11]. Hepatic and metabolic profiles, especially those associated with IR, are higher in PE than in healthy pregnant women [12]. One of the less studied pathways in the PE is the kynurenine pathway (KP), which degrades 95% of the tryptophan (TRP) to kynurenine (KYN) and either its neurotoxic or neuroprotective immunogenic metabolites [13].…”