Maternally transmitted and food-derived glycotoxins: a factor preconditioning the young to diabetes?

Veronica Mericq, Cecilia Piccardo, Weijing Cai, Xue Chen, Li Zhu, Gary E Striker, Helen Vlassara, Jaime Uribarri, Veronica Mericq, Cecilia Piccardo, Weijing Cai, Xue Chen, Li Zhu, Gary E Striker, Helen Vlassara, Jaime Uribarri

Abstract

Objective: Proinflammatory advanced glycation end products (AGEs) found in thermally processed foods correlate with serum AGEs (sAGEs) and promote type 1 and type 2 diabetes in mice. Herein we assess the relationship of maternal blood and food AGEs to circulating glycoxidants, inflammatory markers, and insulin levels in infants up to age 1 year.

Research design and methods: AGEs (N(ε)-carboxymethyllysine [CML] and methylglyoxal derivatives) were tested in sera of healthy mothers in labor (n = 60), their infants, and infant foods. Plasma 8-isoprostane, fasting glucose, insulin, leptin, and adiponectin levels were assessed in 12-month-old infants.

Results: Significant correlations were found between newborn and maternal serum CML (sCML) (r = 0.734, P = 0.001) serum methylglyoxal derivatives (sMGs) (r = 0.593, P = 0.001), and 8-isoprostanes (r = 0.644, P = 0.001). Infant adiponectin at 12 months negatively correlated with maternal sCML (r = -0.467, P = 0.011), whereas high maternal sMGs predicted higher infant insulin or homeostasis model assessment (P = 0.027). Infant sAGEs significantly increased with the initiation of processed infant food intake, raising daily AGE consumption by ∼7.5-fold in year 1.

Conclusions: Maternal blood and food-derived AGEs prematurely raise AGEs in children to adult norms, preconditioning them to abnormally high oxidant stress and inflammation and thus possibly to early onset of disease, such as diabetes.

Figures

Figure 1
Figure 1
Association between circulating AGE and 8-isoprostane levels in mothers and newborns. Correlations between maternal and newborn sCML (A), maternal and newborn sMGs (B), sCML and sMGs at birth (C), and maternal and newborn 8-isoprostane (8-iso) (D). Correlations were estimated by Pearson correlation coefficients.
Figure 2
Figure 2
A and B: Circulating levels of AGEs in infants increase with age. Serum levels of CML (A) and methylglyoxal derivatives (B) were measured by ELISAs in maternal (M) and umbilical cord blood from newborns at delivery (0) and children at age 6 and 12 months. Data shown are means ± SEM. Statistically significant differences are shown between mother and infants at any age (*), between newborn and 6 months (#), newborn and 12 months (§), and 6 and 12 months (&). C and D: At 12 months of age, lower adiponectin levels (D) and higher HOMA levels (C) in infants correlate with higher maternal sAGE levels. HOMA levels were analyzed at 12 months after separation of infants in groups by extreme quartiles of maternal sMGs. *P < 0.05. D: Plasma adiponectin levels in 12-month-old infants were correlated (Pearson correlation coefficient) with maternal sCML levels. Data are means ± SEM.

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