Alterations in the metabolic signature of full-term infants of diabetic mothers

Abstract

Abstract Background Maternal diabetes during pregnancy may alter the metabolomic profile of the offspring, increasing the risk of perinatal complications and potentially predisposing them to adverse metabolic consequences during later life. To assess this risk, we aimed to study the levels of amino acids and acylcarnitines in the cord blood of infants of diabetic mothers (IDMs). Methods Fifty term-IDMs were compared to 25 healthy newborns. Of the diabetic mothers, 37 had gestational diabetes mellitus (GDM), and 13 had pre-gestational diabetes mellitus (PGDM). Amino acid and acylcarnitine concentrations were measured in dried spot samples of cord blood using ultra-performance liquid chromatography–mass spectrometry (UPLC-MS). Results We observed significantly higher levels of valine, aspartic acid, the leucine-to-isoleucine (Leu:Ile), and leucine-to-phenylalanine (Leu:Phe), and decreased values of methionine and the phenylalanine-to-tyrosine (Phe:Tyr) in neonates in the GDM group compared to controls. Neonates of mothers with GDM showed higher levels of C2-carnitine, C5-carnitine, C5:1, and C4-OH (C3-DC) compared to controls. Neonates of mothers with PGDM also showed higher levels of C2-carnitine, C0-carnitine, and C5:1 compared to controls. There were no significant differences in amino acids or acylcarnitine levels between IDMs with GDMs and PGDMs. Principle component analysis (PCA) showed that principal component 1 (PC1) was responsible for the majority of differences between IDMs and controls. PC1 consisted of aspartic, valine, leu:lle, C4-OH(C3-DC), C2-carnitine, C0-carinitine, C5-carnitine, C18:1, and C16:1. Variable importance in projection (VIP) scores based on PLS-DA loadings showed high values for aspartic, valine, leu:lle, Leu:Phe, C4-OH(C3-DC), C2-carnitine, C0-carnitine, C5:1, C5-DC, C18:1, C16:1, C5-carnitine in IDMs, and high values for Met:Phe, methionine, and Phe:Tyr in controls. Conclusion Maternal diabetes leads to alterations in amino acid concentrations and the carnitine shuttle pathway of their offspring.