GC-MS based Gestational Diabetes Mellitus longitudinal study: Identification of 2-and 3-hydroxybutyrate as potential prognostic biomarkers.
Gestational Diabetes Mellitus (GDM) causes severe short- and long-term complications for the mother, fetus and neonate, including type 2-diabetes (T2DM) later in life. In this pilot study, GC-Q/MS analysis was applied for plasma metabolomics fingerprinting of 24 healthy and 24 women with GDM at different stages of gestation (second and third trimester) and postpartum (one and three months). Multivariate (unsupervised and supervised) statistical analysis was performed to investigate variance in the data, identify outliers and for unbiased assessment of data quality. Plasma fingerprints allowed for the discrimination of GDM pregnant women from controls both in the 2nd and 3rd trimesters of gestation. However, metabolic profiles tended to be similar after delivery. Follow up of these women revealed that 4 of them developed T2DM within 2 years postpartum. Multivariate PLS-DA models limited to women with GDM showed clear separation 3 months postpartum. In the 2nd trimester of gestation there was also a clear separation between GDM women that were normoglycemic after pregnancy and those with recognized postpartum T2DM. Metabolites that had the strongest discriminative power between these groups in the 2nd trimester of gestation were 2-hydroxybutyrate, 3-hydroxybutyrate, and stearic acid. We have described, that early GDM comprises metabotypes that are associated with the risk of future complications, including postpartum T2DM. In this pilot study, we provide evidence that 2-hydroxybutyrate and 3-hydroxybutyrate may be considered as future prognostic biomarkers to predict the onset of diabetic complications in women with gestational diabetes after delivery.
Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: danuta.dudzik@ceu.es.
Danuta
D
Dudzik
Department of Clinical Medicine, Faculty of Health Science, Medical University of Bialystok, 37 Szpitalna Street, 15-254, Bialystok, Poland. Electronic address: mzorawski@wp.pl.
Marcin
M
Zorawski
Clinical Department of Perinatology, Public Clinic Hospital, Medical University of Bialystok, 24a Sklodowskiej-Curie Street, 15-276, Bialystok, Poland. Electronic address: mariusz.z.skotnicki@gmail.com.
Mariusz
M
Skotnicki
Clinical Department of Endocrinology, Diabetology and Internal Diseases, Public Clinic Hospital, Medical University of Bialystok, 24a Sklodowskiej-Curie Street, 15-276, Bialystok, Poland. Electronic address: wieslawzarz@wp.pl.
Wieslaw
W
Zarzycki
Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: antogar@ceu.es.
Antonia
A
García
Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: sangulo@ceu.es.
Santiago
S
Angulo
Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: pazloga@ceu.es.
M Paz
MP
Lorenzo
Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: cbarbas@ceu.es.
Coral
C
Barbas
Biochemistry and Molecular Biology, Facultad de Farmacia, Universidad San Pablo CEU, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: pramos@ceu.es.
M Pilar
MP
Ramos
D020155:3-Hydroxybutyric Acid; D015415:Biomarkers; D016640:Diabetes, Gestational; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008137:Longitudinal Studies; D010865:Pilot Projects; D011247:Pregnancy; D011379:Prognosis
D015415:Biomarkers; D020155:3-Hydroxybutyric Acid
2-hydroxybutyrate; 3-hydroxybutyrate; Fingerprinting; Gas chromatography; Gestational diabetes mellitus; Maternal metabolism; Metabolomics; Type 2-diabetes mellitus