Background: 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: HDL; gestational diabetes; metabolomics; obesity; overweight; prediction.
Copyright © American Society for Nutrition 2019.