Associations of Maternal rs1801131 Genotype in MTHFR and Serum Folate and Vitamin B12 with Gestational Diabetes Mellitus in Chinese Pregnant Women.

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B12, with gestational diabetes mellitus (GDM). However, few studies have evaluated the combined effects of these nutrients with OCM related gene polymorphisms on GDM. This study investigated whether OCM related genetic variants modified the associations of folate and B12 with GDM. Logistic regression was used to estimate odds ratios (ORs) for OCM related nutrients and single nucleotide polymorphisms (SNPs) in genes encoding main OCM related enzymes (MTHFR, MTR, and MTRR) on GDM. Higher folate concentrations were associated with increased GDM risk (OR: 1.59; 95% CI: 1.22, 2.13). However, higher B12 concentrations were associated with reduced GDM risk (OR: 0.76; 95% CI: 0.65, 0.92). Pregnancies with MTHFR rs1801131 G alleles had a significantly lower risk of GDM than pregnancies with T alleles (OR: 0.65; 95% CI: 0.47, 0.91) under the dominant model. The genotype-stratified analysis revealed the association between folate and GDM (OR: 1.66, 95% CI: 1.20, 2.30) or B12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM.

Joint effect of urinary arsenic species and serum one-carbon metabolism nutrients on gestational diabetes mellitus: A cross-sectional study of Chinese pregnant women.

BACKGROUND: Growing evidence indicates that arsenic (As) exposure can increase the risk of gestational diabetes mellitus (GDM). However, little is known about As species and GDM and the combined effect of As and one-carbon metabolism (OCM) on GDM. OBJECTIVES: We aimed to examine the associations between As species and GDM and evaluate the potential interactions of folate, vitamin B12, and homocysteine (Hcy) with As species on GDM prevalence. METHOD: We measured levels of arsenite (As3+), arsenate (As5+), dimethylarsinic acid (DMA), and arsenobetaine (AsB) species in urine and folate, vitamin B12, and Hcy in serum from 396 pregnant women in Tianjin, China. The diagnosis of GDM was based on an oral glucose tolerance test. Associations of As species in urine with GDM were evaluated using generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR). Additive interactions of As and OCM with GDM were estimated by determining the relative excess risk due to interaction (RERI). RESULTS: Of the 396 pregnant women, 89 were diagnosed with GDM. Continuous increases in urinary inorganic As were associated with GDM in the GLMs, with adjusted odds ratios of 2.12 (95% CI: 0.96, 4.71) for As3+, and 0.27 (95% CI: 0.07, 0.98) for As5+. The BKMR in estimating the exposure-response functions showed that As3+ and AsB were positively associated with GDM. However, As5+ showed a negative relationship with GDM. Although the additive interactions between As exposure and OCM indicators were not significant, we found that pregnant women with higher urinary As3+ and total As accompanied by lower serum vitamin B12 were more likely to have higher odds of GDM (3.12, 95% CI: 1.32, 7.38 and 3.10, 95% CI: 1.30, 7.38, respectively). CONCLUSIONS: Our data suggest a positive relation between As3+ and GDM but a negative relation between As5+ and GDM. Potential additive interaction of As and OCM with GDM requires further investigation.

Associations of urinary phenolic environmental estrogens exposure with blood glucose levels and gestational diabetes mellitus in Chinese pregnant women.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are considered to be related to diabetes, but studies of the association between phenolic EDCs and gestational diabetes mellitus (GDM) are limited. OBJECTIVES: To assess associations of maternal urinary bisphenol A (BPA), nonylphenol (NP), and 2-tert-octylphenol (2-t-OP) with GDM occurrence. METHODS: A cross-sectional study was performed among 390 Chinese women at 24-28 weeks of gestation. GDM was diagnosed with a 2-h 75-g oral glucose tolerance test (OGTT). BPA, NP, and 2-t-OP concentrations were determined in urine samples. Linear and logistic regression tests evaluated associations of BPA, NP, and 2-t-OP with blood glucose levels and GDM prevalence. RESULTS: The 2-t-OP concentrations in GDM patients were significantly higher than in non-GDM women with median values of 2.23 µg/g Cr and 1.79 µg/g Cr, respectively. No significant difference was observed in BPA and NP. Urinary 2-t-OP was positively associated with blood glucose levels after adjustment for several confounding factors and urinary BPA and NP. Higher 2-t-OP levels were associated with higher odds of GDM (OR: 5.78; 95% CI: 2.04, 16.37), whereas higher NP levels were associated with lower odds (OR: 0.22; 95% CI: 0.05, 0.85) in the adjusted models. In addition, compared to the first quartile of 2-t-OP, the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GDM in the second, third, and fourth quartiles were 2.81 (1.23, 6.42), 3.01 (1.30, 6.93), and 5.49 (2.24, 13.46), respectively. CONCLUSION: Our study indicates that, for the first time to our knowledge, exposure to 2-t-OP is associated with a higher risk of GDM. However, higher NP exposure is associated with lower GDM risk. Further studies are necessary to affirm the associations of 2-t-OP and NP with GDM, and to elucidate the causality of these findings.

Joint effects of folate and vitamin B12 imbalance with maternal characteristics on gestational diabetes mellitus.

BACKGROUND: This study examined whether folate and vitamin B12 imbalance is associated with gestational diabetes mellitus (GDM) and explored interactions between B vitamin imbalance and maternal risk factors for GDM. METHODS: A cross-sectional study was performed in 406 Chinese pregnant women. Serum folate, vitamin B12 , and blood glucose concentrations were measured at 24 to 28 weeks gestation during GDM screening. A diagnosis of GDM was made based on International Association of Diabetes and Pregnancy Study Groups criteria (fasting plasma glucose [FPG] ≥5.1 mM, 1-hour plasma glucose ≥10.0 mM, or 2-hour plasma glucose ≥8.5 mM). Binary logistic regression was used to obtain odds ratios (ORs) after controlling for different confounders. RESULTS: Higher folate levels were associated with higher glucose concentrations and a higher risk of GDM (OR 1.98; 95% confidence interval [CI] 1.00-3.90), whereas higher vitamin B12 levels were associated with lower FPG and a lower risk of GDM (OR 0.30; 95% CI 0.15-0.60). A higher folate: vitamin B12 ratio was associated with higher glucose and a higher risk of GDM (OR 3.08; 95% CI 1.63-5.83). The presence of both a higher folate: vitamin B12 ratio and advanced age further increased the OR to 2.13 (95% CI 1.09-4.15) with a significant additive interaction. Furthermore, a higher folate: vitamin B12 ratio and a higher prepregnancy body mass index (pp-BMI) were synergistically associated with an increased risk of GDM (OR 3.03; 95% CI 1.40-6.57). CONCLUSIONS: An imbalance between folate and vitamin B12 , represented by a higher folate: vitamin B12 ratio, was highly associated with GDM risk, and this association could be further modified by maternal age and pp-BMI.

Small-for-gestational age and its association with maternal blood glucose, body mass index and stature: a perinatal cohort study among Chinese women.

OBJECTIVE: To examine whether maternal low blood glucose (BG), low body mass index (BMI) and small stature have a joint effect on the risk of delivery of a small-for-gestational age (SGA) infant. DESIGN: Women from a perinatal cohort were followed up from receiving perinatal healthcare to giving birth. SETTING: Beichen District, Tianjin, China between June 2011 and October 2012. PARTICIPANTS: 1572 women aged 19-39 years with valid values of stature, BMI and BG level at gestational diabetes mellitus screening (gestational weeks 24-28), glucose challenge test <7.8 mmol/L and singleton birth (≥37 weeks' gestation). MAIN OUTCOME MEASURES: SGA was defined as birth weight <10th centile for gender separated gestational age of Tianjin singletons. RESULTS: 164 neonates (10.4%) were identified as SGA. From multiple logistic regression models, the ORs (95% CI) of delivery of SGA were 0.84 (0.72 to 0.98), 0.61 (0.49 to 0.74) and 0.64 (0.54 to 0.76) for every 1 SD increase in maternal BG, BMI and stature, respectively. When dichotomises, maternal BG (<6.0 vs ≥6.0 mmol/L), BMI (<24 vs ≥24 kg/m(2)) and stature (<160.0 vs ≥160.0 cm), those with BG, BMI and stature all in the lower categories had ∼8 times higher odds of delivering an SGA neonate (OR (95% CI) 8.01 (3.78 to 16.96)) relative to the reference that had BG, BMI and stature all in the high categories. The odds for an SGA delivery among women who had any 2 variables in the lower categories were ∼2-4 times higher. CONCLUSIONS: Low maternal BG is associated with an increased risk of having an SGA infant. The risk of SGA is significantly increased when the mother is also short and has a low BMI. This may be a useful clinical tool to identify women at higher risk for having an SGA infant at delivery.

The association between glucose challenge test level and fetal nutritional status.

OBJECTIVE: To examine the relationship between maternal glucose challenge test (GCT) levels and fetal nutritional status index (FNSI: a ratio of child's birth weight (kg) over squared maternal height (m(2)). METHODS: A total of 2193 women from the Beichen district, Tianjin, China, who had 50 g GCT at gestational age 24-28 weeks, gave a full-term singleton birth between June 2011 and October 2012, and with both maternal height and birth weight measures are included in this report. RESULTS: Approximately 28.0% of women had a GCT ≥ 7.8 mmol/L. The newborns of mothers with a GCT ≥ 7.8 mmol/L had significantly higher level of FNSI ([kg/m(2)], boys: 1.336 versus 1.296, p < 0.001; girls: 1.312 versus 1.268, p < 0.0001). Logistic regression results, after adjustment for maternal age, residence, education, nationality, history of disease and reproduction, insurance and gestational age, indicated that every unit increase in FNSI was associated with approximately threefold higher odds (OR [95% CI]: 3.6 [1.5, 8.9]) of being in GCT ≥ 7.8 mmol/L for women giving birth as boys and fivefold higher odds (5.9 [2.5, 14.1]) for giving birth as girls. CONCLUSIONS: Women with a GCT ≥ 7.8 mmol/L have babies with a higher FNSI, suggesting that these infants may be overnourished before birth and may increase cardiovascular risk in their future.