First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes

Abstract

■ AbstractBACKGROUND: Current screening methods for gestational diabetes mellitus (GDM) are insufficient in detecting the risk of GDM in the first trimester of the pregnancy. Recent metabolomic studies have detected altered amino acid and acylcarnitine concentrations in type 2 diabetes (T2D). Because of the similarities between T2D and GDM, the determination of these metabolites may be useful in early screening for GDM. AIM: To evaluate the association between GDM and first-trimester maternal serum concentrations of ten amino acids and 31 acylcarnitines. METHODS: This retrospective case-control study included data from pregnant women screened at Oulu University Hospital between 1. 1.2008 and 31.12.2011. A total of 31,146 women participated voluntarily in a first-trimester combined screening (for chromosomal abnormalities). The study population included 69 women who developed GDM during pregnancy and 295 women without diabetes before or after pregnancy. The serum concentrations of ten amino acids and 31 acylcarnitines were analyzed from frozen serum samples taken in the first-trimester screening. Multiple of median (MoM) values were compared between the two groups. RESULTS: In the GDM group, serum levels of arginine were significantly higher (1.13 MoM vs. 0.97 MoM), and those of glycine (0.93 MoM vs. 1.03 MoM) and 3-hydroxyisovalerylcarnitine (0.86 MoM vs. 1.03 MoM) significantly lower compared to the control group (all p < 0.01). In each case, arginine, glycine, and 3-hydroxy-isovaleryl-carnitine would have detected 46%, 32%, and 39% of GDM cases, with a false-positive rate of 20%. Combining these three metabolites with the first-trimester serum marker pregnancy-associated plasma protein A (PAPP-A) and prior risk (age, BMI, and smoking) achieved a detection rate of 72%. CONCLUSION: There are significant differences in the serum levels of arginine, glycine, and 3-hydroxy-isovalerylcarnitine between controls and women who subsequently develop GDM. These differences were already existent in the first trimester of the pregnancy. The use of metabolites in combination with prior risk and first-trimester PAPP-A represents a reliable method to identify women at risk of GDM.

Diabetes Leads to Alterations in Normal Metabolic Transitions of Pregnancy as Revealed by Time-Course Metabolomics

“…Alterations in glycine/serine/threonine serum metabolism in GDM have previously been reported during the third trimester of pregnancy [ 52 ]. Glutamine and threonine are decreased during late gestation [ 53 , 54 , 55 ], while glycine is significantly decreased during the first and third trimesters with GDM, as well as in non-pregnant cohorts with T2D [ 36 , 37 , 38 , 39 , 56 , 57 ]. Glutamine showed a significant interaction effect, with decreases in early gestation trending towards significance following a post-hoc analysis ( p = 0.09).…”

Glycosylated fibronectin as a first trimester marker for gestational diabetes

“…Previous studies have shown that maternal serum biomarkers are altered already in the first trimester of pregnancy in women who subsequently develop GDM. Studied markers include metabolites such as glycine and arginine, fatty acids, sex hormone binding globulin (SHBG), inflammatory markers, adipocyte-derived markers, placenta-derived markers, placental exomes and glycosylated (Sambucus nigra lectinreactive) fibronectin [5][6][7][8][9][10][11][12].…”

Mid-late pregnancy maternal glycolipids in gestational diabetes mellitus (GDM) fluctuated in glycosylated hemoglobin levels of 5.5%-6.4% associated with umbilical cord blood of amino acid and carnitine profiles: a nested case-cohort observational study

“…Foetal metabolism, as indicated by carnitine levels and amino acids, is related to the risk of preterm infants, maternal gestational age and neonatal development [23,24] . Dysglycaemia is an important link between maternal serum amino acids and carnitines [25] , maternal obesity/overweight [26] and maternal and foetal lipid pro les [27] . We explored the relationship between GDM uctuated in glycosylated hemoglobin levels of 5.5%-6.4%(as GDM a ) and neonatal carnitine levels and amino acids and their potential in uence on foetal growth.…”