Prospective Study Of Protein Nutritional Status During Pregnancy And The Risk Of Gestational Diabetes Mellitus

Background: Gestational diabetes mellitus(GDM)is a prevalent pregnancy complication that can have short-and long-term adverse effects on both mothers and their offspring.Protein is an essential nutrient for maternal and infant health.However,previous epidemiological studies have drawn inconsistent conclusions regarding the role of dietary protein in GDM.Moreover,there is insufficient evidence regarding the association between dietary amino acid intake during pregnancy and GDM risk.With advances in detection technology,more studies have investigated the link between circulating amino acid levels and GDM risk.It was found that the circulating amino acid levels in GDM pregnant women were significantly different from those in healthy pregnant women.However,previous studies have only detected limited types of amino acids and metabolites,or lacked absolute quantitative data.Objective: To investigate the association between protein nutritional status during pregnancy and the risk of GDM in a population of Chinese pregnant women in terms of dietary protein intake,dietary amino acid intake,and plasma amino acid and metabolite levels.Methods: Part I and Part II were designed using a prospective cohort study,with a sample of 2006 pregnant women enrolled in the Tongji Birth Cohort(TJBC)from 2018 to 2022.Dietary intake was assessed in early pregnancy using a semi-quantitative food frequency questionnaire.The diagnosis of GDM is made using a 75 g 2-hour oral glucose tolerance test during 24–28 weeks of gestation.The association of dietary protein and amino acid intake during pregnancy with the risk of GDM was assessed by using multivariate Logistic regression.Part III was designed using a nested case-control study that included 110 GDM cases and 110 healthy controls matched 1:1 according to maternal age(± 3 years)and gestational week of blood collection(± 3 weeks).Ultra-performance liquid chromatography-tandem mass spectrometry was used to determine plasma amino acid and metabolite levels in early pregnancy.The determinants of plasma amino acid and metabolite levels were assessed by multiple linear regression.Further,multivariate conditional Logistic regression with the least absolute shrinkage and selection operator was utilized to determine the optimal amino acid metabolic markers of GDM,and the metabolite risk score(MRS)was constructed to assess their predictive performance.Results:(1)Among the 2006 participants,378 pregnant women(18.8%)were diagnosed with GDM.The median dietary total protein intake was 53.64 g/day,with animal and plant protein intakes of 18.64 g/day and 34.39 g/day,respectively.Compared with the lowest quartile group(Q1),the odds ratio(OR)and 95% confidence interval(CI)for the risk of GDM in the second quartile(Q2)to the highest quartile(Q4)of dietary total protein intake were 1.49(1.03,2.15),1.90(1.29,2.82),and 1.78(1.10,2.88),respectively.The OR and 95% CI of animal protein intake in Q2 to Q4 groups were 1.37(0.94,2.00),1.85(1.20,2.87),and 1.96(1.10,3.50),respectively.The dose-response analysis revealed significant nonlinear relationships of dietary total protein and animal protein intake with the risk of GDM.Further analysis of dietary protein from different sources found that protein intake from red meat,dairy products,and refined grains were associated with an increased risk of GDM.Conversely,protein intake from whole grains in the Q2 group was associated with a reduced risk of GDM.(2)Compared to the Q1 group,the risk of GDM was significantly increased in the Q3 group for dietary leucine,lysine,phenylalanine,serine,threonine,and valine intake,with OR and 95% CI of 1.60(1.08,2.37),1.66(1.12,2.48),1.56(1.07,2.29),1.53(1.04,2.26),1.50(1.02,2.21),and 1.47(1.01,2.15),respectively.In addition,there was a linear positive association between dietary proline intake and the risk of GDM(P for trend = 0.025),with OR and 95% CI of 1.45(1.02,2.07),1.51(1.03,2.22),and 1.72(1.12,2.67)for the Q2 to Q4 groups compared with the Q1 group,and each standard deviation increment in dietary proline intake was associated with a 20% increase in the risk of GDM(OR: 1.20;95% CI: 1.02,1.41).(3)Maternal age,pre-pregnancy BMI,educational level,monthly household income,primiparity,physical activity during pregnancy,passive smoking during pregnancy,and dietary protein intake from different sources may be important determinants of maternal plasma amino acid and metabolite levels.Eight metabolites were selected as the best subset for predicting the GDM risk,with 5-L-glutamyl-L-alanine,asparagine,homocitrulline,kynurenic acid,N-acetyl-L-glutamine,and N-acetyl-L-tyrosine being positively associated with GDM risk,while glycine and succinic acid being negatively associated with GDM risk.The MRS,which consists of these metabolites,was strongly associated with an increased risk of GDM.In addition,combining MRS with traditional risk factors resulted in a significant improvement in the predictive performance of GDM risk.Conclusions: Dietary total protein and animal protein intake during pregnancy showed significantly positive associations with GDM risk,and nonlinear associations existed.Dietary intake of leucine,lysine,phenylalanine,proline,serine,threonine,and valine during pregnancy was positively associated with the risk of GDM.In addition,the optimal amino acid metabolic markers identified in this study could help to improve the prediction of GDM risk.