title: First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry.
abstract: OBJECTIVE
  Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve first-trimester prediction of GDM among obese and non-obese women compared with single markers.
  
  
  METHODS
  A nested case-control study was performed on first-trimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI ≥27 kg/m(2)) and a non-obese group (BMI <27 kg/m(2)). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay.
  
  
  RESULTS
  After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, non-obese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone.
  
  
  CONCLUSIONS
  Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.|The Danish Diabetes Academy, Odense, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Ravnsborg
authors.affiliation: Department of Obstetrics and Gynaecology, Odense University Hospital, Odense, Denmark.
authors.forename: Lise Lotte T
authors.initials: LL
authors.lastname: Andersen
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Natacha D
authors.initials: ND
authors.lastname: Trabjerg
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.|The Danish Diabetes Academy, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
authors.affiliation: The Danish Diabetes Academy, Odense, Denmark.|Department of Obstetrics and Gynaecology, Odense University Hospital, Odense, Denmark.|Department of Endocrinology, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Dorte M
authors.initials: DM
authors.lastname: Jensen
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. Martin.Overgaard@rsyd.dk.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Martin.Overgaard@rsyd.dk.
authors.forename: Martin
authors.initials: M
authors.lastname: Overgaard
mesh_terms: D054392:Adipokines / Q000097:blood; D001053:Apolipoproteins / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D016640:Diabetes, Gestational / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D009765:Obesity / Q000097:blood; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood
chemical_list: D054392:Adipokines; D001053:Apolipoproteins
keywords: Adipokine; Apolipoprotein; Early prediction; Gestational diabetes mellitus; Obesity; Targeted MS
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