Divergent changes in serum branched-chain amino acid concentrations and estimates of insulin resistance throughout gestation in healthy women

Authors: ALLMAN, BRITTANY - Arkansas Children'S Nutrition Research Center (ACNC); DIAZ, EVA - Arkansas Children'S Nutrition Research Center (ACNC); ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC); BORSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2020
Publication Date: 4/10/2020
Citation: Allman, B.R., Diaz, E.C., Andres, A., Borsheim, E. 2020. Divergent changes in serum branched-chain amino acid concentrations and estimates of insulin resistance throughout gestation in healthy women. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa096.
DOI: https://doi.org/10.1093/jn/nxaa096

Interpretive Summary: High blood levels of branched-chain amino acids (BCAA; LEU, leucine; ISO, isoleucine; VAL, valine) are often related to higher levels of resistance to the blood sugar-controlling hormone insulin, when they are measured at one time point in populations such as pregnant women with obesity. However, the relationship between the change in BCAA concentration and the change in insulin resistance throughout the duration of pregnancy (a period where insulin resistance typically increases) has not yet been described. In a study tracking metabolism of pregnant women through the third trimester, it was found that LEU and ISO concentrations were positively correlated with measurements of insulin resistance (homeostatic model assessment of insulin resistance, HOMA2-IR) at early and late pregnancy. However, when body fat percentage was factored in, these relationships in early pregnancy decreased or disappeared. We also found that the change in LEU was negatively associated with the change in HOMA2-IR from from early to late pregnancy. Lastly, it was found that a greater decrease in LEU was associated with lower insulin sensitivity. For the first time, we report divergent changes in BCAA blood concentration and insulin resistance throughout pregnancy, which is the opposite of the current dogma. The results from the current study highlight the importance of taking metabolic measurements over the entire course of pregnancy (rather than one time point) when determining relationships between blood amino acids (such as the BCAA) and the body's ability to control blood sugar through the hormone insulin.

Technical Abstract: Branched-chain amino acid (BCAA) concentrations in the blood have been correlated with insulin resistance, but this relation throughout gestation (period in which insulin resistance typically increases) is unclear. The objective of this study was to determine the associations between changes in BCAA concentrations and estimates of insulin resistance throughout gestation. Serum BCAA (Leu, Ile, Val) concentrations and insulin resistance/sensitivity [i.e., homeostatic model assessment-2 of insulin resistance (HOMA2-IR), estimated metabolic clearance rate (MCR) of glucose, and estimated first- and second-phase insulin responses] were assessed at early (EP; 8.5 +/- 0.2 wk) and/or late (LP; 29.2 +/- 0.8 wk) pregnancy in 53 healthy women from the Glowing cohort. Adjusted Spearman correlations were used to evaluate the association between BCAA and insulin resistance/sensitivity measures at EP and LP, adjusted for body fat percentage and gestational weight gain (GWG). A multiple linear regression analysis was used to assess the association between changes in HOMA2-IR and BCAAs throughout gestation. Groups were made post hoc based on the mean percentage change (10% decrease) in Leu throughout gestation, creating a group with a >=10% decrease in LeuLP-EP (BELOW) and a <10% decrease in LeuLP-EP (ABOVE), and Student's t tests were performed to assess differences between groups. Leu and Ile concentrations positively correlated with HOMA2-IR at both time points, but these relations at EP disappeared/weakened when adjusted for body fat percentage. From EP to LP, the change in Leu (LeuLP-EP) was negatively associated with the change in HOMA2-IR (HOMA2-IRLP-EP) (B = -0.037, P = 0.006). MCR was lower in the BELOW group compared with the ABOVE group, whereas there was no difference in HOMA2-IR between groups. In this pregnancy cohort, BCAA concentrations decreased throughout gestation, whereas the mean insulin resistance did not change. These data do not support a connection between changes in blood BCAA concentrations and estimates of insulin resistance in pregnant women.