Exploring the mediating effects of amino acids on BMI and gestational diabetes mellitus: a longitudinal population-based cohort study

Abstract

Objective: To investigate the associations between pre-pregnancy BMI, amino acid metabolism in early pregnancy, and glucose levels/gestational diabetes mellitus (GDM) in later pregnancy. We also examined the mediating effects of amino acids on BMI and glucose.

Methods: The cohort study examined the association between BMI, first-trimester amino acids, and glucose/GDM among 1074 pregnant women. Regression analyses detected changes in amino acid levels and glucose measurements from oral glucose tolerance test (OGTT) at the 10th, 50th, and 90th percentiles. A mediation analysis was conducted to determine if amino acids mediated the relationship between BMI and glucose/GDM.

Results: Four essential amino acid concentrations (leucine, phenylalanine, threonine, and valine) increased significantly with increasing BMI (P < 0.05). Additionally, overweight women exhibited higher levels of non-essential amino acids (alanine, arginine, asparagine, aspartate, proline, tyrosine) and ornithine than underweight and normal-weight women. Women with GDM demonstrated higher levels of leucine, valine, alanine, asparagine, proline, and tyrosine compared to those without (P < 0.05). Fasting blood glucose (OGTT0) increased by 0.07 mmol/L when alanine levels increased by 50%. Similarly, increasing asparagine and leucine levels by 50% led to a 0.24 mmol/L increase in 1-hour postprandial blood glucose (OGTT1). A 50% rise in alanine, asparagine, and leucine levels led to average increases of 0.31, 0.19, and 0.21 mmol/L in mean 2-h postprandial blood glucose (OGTT2). These associations were statistically significant at the upper 90th percentile of the OGTT2 distribution. 50% increase in valine was correlated with a 0.22 mmol/L increase in mean OGTT2. The levels of alanine accounted for 11.76%, 8.08%, and 11.38% of the associations between BMI and GDM, OGTT0, and OGTT2, respectively. Additionally, the indirect effect of BMI-associated OGTT2 on leucine levels was estimated to be 5.39 percent.

Conclusion: Amino acid metabolism is correlated with BMI, GDM, and glucose levels. Notably, BMI and GDM/glucose intolerance are significantly mediated by alanine and leucine levels. This suggests a new way to study why overweight or obese mothers are more likely to develop GDM and glucose intolerance.

Keywords: BMI; amino acid metabolism; cohort study; gestational diabetes mellitus; glucose; mediating effect.

Figure 1

Distribution changes in OGTT0 as function of 50% increase in amino acids. The models were adjusted for maternal age, parity, level of education, family income, family history of diabetes, polycystic ovary syndrome, passive smoking, folic acid supplements prepare for pregnancy, pre-pregnancy BMI, fasting blood for amino acid metabolism, weight gain during pregnancy before OGTT, gestational age for amino acids metabolism detection.

Figure 2

Distribution changes in OGTT1 as function of 50% increase in amino acids. The models were adjusted for maternal age, parity, level of education, family income, family history of diabetes, polycystic ovary syndrome, passive smoking, folic acid supplements prepare for pregnancy, pre-pregnancy BMI, fasting blood for amino acid metabolism, weight gain during pregnancy before OGTT, gestational age for amino acids metabolism detection.

Figure 3

Distribution changes in OGTT2 as function of 50% increase in amino acids. The models were adjusted for maternal age, parity, level of education, family income, family history of diabetes, polycystic ovary syndrome, passive smoking, folic acid supplements prepare for pregnancy, pre-pregnancy BMI, fasting blood for amino acid metabolism, weight gain during pregnancy before OGTT, gestational age for amino acids metabolism detection.

Figure 4

Mediation analysis with standardized coefficients of BMI, amino acids and GDM or glucose. The models were adjusted for maternal age, parity, level of education, family income, family history of diabetes, polycystic ovary syndrome, passive smoking, folic acid supplements prepare for pregnancy, fasting blood for amino acid metabolism, weight gain during pregnancy before OGTT, gestational age for amino acids metabolism detection.All models were found to be statistically significant (P < 0.05). (A), mediating effects of Ala on BMI and GDM; (B), mediating effects of Ala on BMI and OGTT0; (C), mediating effects of Ala on BMI and OGTT2; (D), mediating effects of Leu on BMI and OGTT2.