Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus

Abstract

Aims. The objective of the study was to measure one of the circulating Advanced Glycation End Products (AGEs) -Nε-(carboxymethyl)lysine (CML) -in a case-control study (n = 307) of pregnant women with gestational diabetes mellitus (GDM) and physiological pregnancies and to ascertain the factors contributing to CML levels and the potential relevance of CML for selected perinatal and postpartum outcomes. Methods. All subjects underwent oGTT between 24 th and 30 th week of gestation and GDM was diagnosed according to WHO criteria. CML was determined by ELISA using commercial kit. Results. Unadjusted and plasma protein adjusted CML levels were significantly higher in women with GDM compared to healthy controls (P = 0.00043 and P = 1x10 -5 , respectively, Mann-Whitney). CML was significantly inversely correlated with both pre-and mid-gestational BMI, however, differences between GDM and control group remained significant even after adjustment for BMI. CML levels correlated with 1-h and 2-h post-load glycaemia during oGTT. Conclusion. In conclusion, we found statistically significantly higher protein-and BMI-normalised CML levels measured during 24-30 th week of gestation in women with GDM compared to healthy pregnant controls. Further studies are warranted to comprehensively asses the spectrum of AGEs in GDM and their relevance to future metabolic health of mother and offspring.

The relationship between advanced glycation end products and gestational diabetes: A systematic review and meta-analysis

“…Regarding the geographical distribution, the review included seven studies from Europe [30][31][32][33][34][35][36], seven studies from Asia [37][38][39][40][41][42][43] and two studies from Latin America [44,45]. Thirteen of these studies employed case-control design [30,32,33,[35][36][37][38][39][40][41][42][43][44] whereas the rest three studies were cross-sectional in design [31,34,45]. Specifically, the meta-analysis of AGEs involved 774 cases and 834 controls.…”

“…The systematic review and meta-analysis involved studies that reported the outcome measures at both first and second trimesters [32], first and third trimesters [36], second trimester [30,31,34,41,44], second and third trimesters [38,42], and third trimester of pregnancy [33,35,37,39,40] whereas two studies did not specify gestational period during sample collection [43,45]. Blood sample was collected from 13 studies [30,31,33,[35][36][37][38][39][40][42][43][44][45], skin sample from two studies [32,34], and placenta sample from one study [41] ( Table 1). For analysis of specific AGEs and metabolic biomarkers, five and four studies were included to generate the pooled estimates of HOMA-IR [31,37,42,43,45], and HbA1c [31,33,37,43], respectively.…”

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

“…in addition, other studies have identified that insulin therapy does not improve fetal or newborn metabolic outcomes (8), and that it can cause alterations in the placenta (9), indicating factors other than glucose may be involved in the pathophysiology of GdM. in a number of studies, advanced glycation end products (AGEs) have been identified to be present in higher levels in women suffering from GdM (10,11) and these products are associated with poor fetal outcomes (12). aGes are reportedly involved in increasing the permeability of retinal vascular and endothelial cells (13,14).…”

Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes

“…Results -including our earlier study of carboxymethyl lysine in GDM pregnancy and postpartumshowed mostly increased AGEs plasma levels in GDM compared to healthy pregnant women [9][10][11][12]. Formation of AGEs may be limited by the action of Bprotective^pathways that either metabolize existing precursors of AGEs (e.g.…”