Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial

Danielle E Haslam; Jun Li; Liming Liang; Marijulie Martinez; Cristina Palacios; Maria A Trak-Fellermeier; Paul W Franks; Kaumudi Joshipura; Shilpa N Bhupathiraju

doi:10.3390/metabo10070284

Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial

Metabolites. 2020 Jul 10;10(7):284. doi: 10.3390/metabo10070284.

Authors

Danielle E Haslam^{1

2

3}, Jun Li^{3

4}, Liming Liang^{4

5}, Marijulie Martinez⁶, Cristina Palacios⁷, Maria A Trak-Fellermeier⁷, Paul W Franks⁸, Kaumudi Joshipura^{4

6}, Shilpa N Bhupathiraju^{1

2

3}

Affiliations

¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
² Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
³ Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA.
⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA.
⁵ Department of Biostatistics, Harvard T.H. Chan School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA.
⁶ Center for Clinical Research and Health Promotion, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936-5067, Puerto Rico.
⁷ Dietetics and Nutrition Department, Robert Stempel College of Public Health & Social Work, Florida International University, 11200 SW 8th Street AHC5, Miami, FL 33199, USA.
⁸ Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12, SE-214 28 Malmö, Sweden.

Abstract

The oral glucose tolerance test (OGTT) is used to diagnose gestational and other types of diabetes. We examined metabolite changes during an OGTT, and how a comprehensive diet and physical activity intervention may influence these changes in a population of overweight/obese Hispanic pregnant women. Integration of changes in metabolites during an OGTT may help us gain preliminary insights into how glucose metabolism changes during pregnancy. Among women from the Pregnancy and EARly Lifestyle improvement Study (PEARLS), we measured metabolites during a multipoint OGTT (fasting, 30, 60 and 120 min) at early and mid-pregnancy. Metabolite levels were measured by liquid chromatography-mass spectrometry in plasma samples in the lifestyle intervention (n = 13) and control (n = 16) arms of the study. A total of 65 candidate metabolites were selected that displayed changes during an OGTT in previous studies. Paired and unpaired t-tests were used to examine differences in Δfast-120 min: (1) at early and mid-pregnancy; and (2) by intervention assignment. We applied principal component analysis (PCA) to identify those metabolites that differed by intervention assignment and OGTT time points. Most of the characteristic changes in metabolites post-OGTT were similar at both gestational time points. PCA identified characteristic metabolite patterns associated with OGTT time points at both early and mid-pregnancy. These metabolites included ketone bodies, tryptophan, acyl carnitines, polyunsaturated fatty acids, and biomarkers related to bile acid, urea cycle, arginine, and proline metabolism. PCA identified distinct Δfast-120 min in fatty acid, acyl carnitine, bile acid, ketone body, and amino acid levels at mid- compared to early pregnancy. Participants in the intervention group did not display mean decreases in Δfast-120 min of several long-chain acyl carnitines that were observed in the control group. These findings provide preliminary insight into metabolites, whose role in increased insulin resistance during pregnancy, should be explored further in future studies.

Keywords: GDM; OGTT; diet; metabolomics; omics; physical activity; pregnancy.

Abstract

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