Plasma Amino Acids in Early and Mid-Pregnancy With Subsequent Risk of Gestational Diabetes and Cardiometabolic Markers – Both Type of Amino Acids and Gestational Timing Matter

OBJECTIVES: To prospectively evaluate associations of plasma amino acids (AAs) in early and mid-pregnancy with gestational diabetes mellitus (GDM) risk and cardiometabolic biomarkers in a longitudinal U.S. multiracial pregnancy cohort. METHODS: We conducted a nested case-control study within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. Individual AAs at gestational weeks (GW) of 10–14, 15–26, 23–31, and 33–39 were assessed among 107 GDM cases (mean GW for GDM ascertainment: 27.4) and 214 controls matched on age, race/ethnicity, and gestational age at sample collection. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations of plasma AAs at 10–14 GW and 15–26 GW with subsequent risk of GDM, adjusting for major covariates. We estimated Spearman's partial correlation coefficients between AAs at 10–14 GW and fasting cardiometabolic markers at 15–26 GW. RESULTS: At 10–14 GW, each SD increment in glycine levels was related to a 45% lower risk of GDM (adjusted OR, 95% CI: 0.55, 0.39–0.79), whereas each SD increase in alanine, aspartic acid, and glutamic acid was associated with a 43% (aOR, 95% CI: 1.43, 1.08–1.88), 41% (aOR, 95% CI: 1.41, 1.11–1.80), and 39% (aOR, 95% CI: 1.39, 0.98–1.98) greater risk of GDM, respectively. At 15–26 GW, similar findings to those at GW 10–14 were observed for glycine, alanine, and aspartic acid. In addition, each SD increment in glutamine-to-glutamic acid-ratio was related to a 50% lower risk of GDM (OR, 95% CI: 0.50, 0.26–0.94). By contrast, higher levels of branched-chain AA (BCAA) isoleucine and aromatic AAs tyrosine and phenylalanine were associated with a higher risk of GDM (OR, 95% CI: 1.64, 1.19–2.27 for isoleucine; 1.56, 1.16–2.09 for tyrosine; and 1.15, 0.87–1.53 for phenylalanine). Higher levels of glycine and lower levels of alanine, BCAA, and aromatic AAs were associated with a more favorable cardiometabolic biomarker profile. CONCLUSIONS: Associations of AAs with GDM differed by both types of AAs and timing over pregnancy. These findings suggest potentially important roles of glycine in both early- and mid-pregnancy, and BCAA and aromatic AAs in mid-pregnancy in the development of GDM and maternal cardiometabolic profiles. FUNDING SOURCES: The Eunice Kennedy Shriver NICHD, American Recovery and Reinvestment Act.