Reliable biomarkers for gestational diabetes mellitus (GDM) would be beneficial in the early prevention of adverse metabolic outcomes during pregnancy and beyond.
Objectives
The objective of this study was to investigate whether the early pregnancy serum metabolic profile differs in women developing GDM from those remaining healthy. Furthermore, we evaluated the potential of these metabolites to act as predictive markers for GDM.
Methods
This was a prospective study investigating overweight and obese [prepregnancy BMI (in kg/m2) =25 and >30, respectively] pregnant women (prepregnancy median BMI: 28.5; IQR: 26.4–31.5;n = 357). Fasting serum samples were analyzed with a targeted NMR approach in early pregnancy (median: 14.3 weeks of gestation). GDM was diagnosed on the basis of a 2-h, 75-g oral-glucose-tolerance test at a median of 25.7 weeks of gestation.
Results
In early pregnancy, 78 lipid metabolites differed in women who later developed GDM (n = 82) compared with those who remained healthy (n = 275) (ANCOVA, adjusted for confounding factors and corrected for multiple comparisons; false discovery rate <0.05). Higher concentrations of several-sized VLDL particles and medium- and small-sized HDL particles, and lower concentrations of very large-sized HDL particles, were detected in women developing GDM. Furthermore, concentrations of amino acids including 2 branched-chain amino acids, isoleucine and leucine, and GlycA, a marker for low-grade inflammation, were higher in women who developed GDM. Receiver operating characteristic analysis revealed that the most predictive marker for GDM was a higher concentration of small-sized HDL particles (AUC: 0.71; 95% CI: 0.67, 0.77;P < 0.001).
Conclusions
We identified a distinct early pregnancy metabolomic profile especially attributable to small HDL particles in women developing GDM. The aberrant metabolic profile could represent a novel way to allow early identification of this most common medical condition affecting pregnant women. This trial was registered at clinicaltrials.gov as NCT01922791.
Keywords
gestational diabetes
metabolomics
overweight
obesity
prediction
HDL
Abbreviations used:
BCAA
branched-chain amino acid
BH
Benjamini–Hochberg
GDM
gestational diabetes mellitus
GlycA
glycoprotein acetylation
OGTT
oral-glucose-tolerance test
PCA
principal component analysis
ROC
receiver operating characteristic
Cited by (0)
The clinical trial was supported by the State Research Funding for university-level health research in the Turku University Hospital Expert Responsibility Area, Academy of Finland (258606); the Diabetes Research Foundation; and the Juho Vainio Foundation. Funding to the University of Turku for the metabolomics analyses and reporting was provided by Janssen Research & Development, LLC.
Author disclosures: KM, TV, OP NH, EK, and KL, no conflicts of interest.
The study sponsors were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.
Data sharing: Publicity about the data sets generated during the current study would limit the ongoing study; therefore, the data are only available from the corresponding author upon reasonable request.
