title: First-Trimester Maternal Serum Amino Acids and Acylcarnitines Are Significant Predictors of Gestational Diabetes.
abstract: 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.
  
  
  OBJECTIVE
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, PL 24, 90100, Oulu University Hospital, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Nevalainen
authors.affiliation: Perkin Elmer, PL 10, 20101, Turku, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Sairanen
authors.affiliation: Perkin Elmer, PL 10, 20101, Turku, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Appelblom
authors.affiliation: National Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Gissler
authors.affiliation: Department of Obstetrics and Gynecology, PL 52, 20521, Turku University Hospital, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Timonen
authors.affiliation: Department of Obstetrics and Gynecology, PL 24, 90100, Oulu University Hospital, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Ryynänen
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D015536:Down-Regulation; D005260:Female; D005387:Finland / Q000453:epidemiology; D005998:Glycine / Q000097:blood*; D006785:Hospitals, University; D006801:Humans; D062145:Maternal Serum Screening Tests; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012189:Retrospective Studies; D012306:Risk; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: C098116:3-hydroxyisovalerylcarnitine; D015415:Biomarkers; D001120:Arginine; D002331:Carnitine; D005998:Glycine