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Rev Diabet Stud, 2016, 13(4):236-245 DOI 10.1900/RDS.2016.13.236

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

Jaana Nevalainen1, Mikko Sairanen2, Heidi Appelblom2, Mika Gissler3, Susanna Timonen4, Markku Ryynänen1

1Department of Obstetrics and Gynecology, PL 24, 90100, Oulu University Hospital, Finland
2Perkin Elmer, PL 10, 20101, Turku, Finland
3National Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland
4Department of Obstetrics and Gynecology, PL 52, 20521, Turku University Hospital, Finland
Address correspondence to: Jaana Nevalainen, e-mail: marttjaa@paju.oulu.fi

Manuscript submitted July 25, 2016; resubmitted August 26, 2016; accepted October 21, 2016.

Keywords: gestational diabetes, acylcarnitine, arginine, glycine, 3-hydroxy-isovalerylcarnitine


BACKGROUND: 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-hydroxy-isovalerylcarnitine (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.

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