Comprehensive Genetic and Pathway Analysis of Gestational Diabetes: A Multidimensional Bioinformatics Approach

Objectives: Studies on the relationship between vitamin B12 and gestational diabetes mellitus (GDM) have shown different results. Given the lack of research in this area in Iran and the inconsistent findings of studies carried out in other nations, this study was conducted in light of the significance of the problem, particularly with regard to the health of expectant mothers. Materials and Methods: This case-control study was performed on 120 pregnant women referred to Ayatollah Rouhani hospital in Babol, private offices, and health centers to evaluate the vitamin B12 level in women with and without GDM. GDM was defined as 1) after oral ingestion of 75g glucose, fasting plasma glucose level (PGL) >92 mg/dL, 1-hour PGL >180mg/dL, or 2-hour PGL >153mg/ dL during 24-28 weeks of gestational age, or 2) in the 100-g oral glucose tolerance test (OGTT), PGL >195 mg/dL, one-hour PGL >180 mg/dL, 2-hour PGL >155, and 3-hour PGL >140, and GDM was diagnosed if there were at least 2 out of 4 mentioned cases. According to the above definition, pregnant women with GDM were placed in the case group, while those without GDM were placed in the control group. After 8 hours of fasting, intravenous blood samples were taken and sent to the laboratory for measurement, and vitamin B12 deficiency was considered <99 pg/dL after 28 gestational weeks. Results: Vitamin B12 deficiency was prevalent in 14.2% of 120 pregnant women studied. Vitamin B12 deficiency was more common in GDM women than in non-GDM women (58.8%-41.2%). A normal level of vitamin B12 could act as a protective factor against GDM. The vitamin B12 levels increased in the 30- to 40-year-old women with GDM. In other age groups, vitamin B12 levels were higher in non-GDM women than in GDM women. Among 17 women with vitamin B12 deficiency, 52.9% had a fasting PGL >92. Conclusions: The results of the present study suggest that measuring vitamin B12 levels may aid in the early diagnosis of GDM and prevent maternal and fetal complications.

OBJECTIVETo investigate the association of folate and vitamin B12 in early pregnancy with gestational diabetes mellitus (GDM) risk.RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association.RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (Ptrend = 0.021). Vitamin B12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B12 with GDM was observed.CONCLUSIONSHigher maternal RBC folate and vitamin B12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B12 is not significantly associated with 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.

The relationship between vitamin B12 and gestational diabetes mellitus (GDM) remains controversial. To comprehensively evaluate the relationship between vitamin B12 and GDM, and to provide more information on GDM prevention, this study provides a systematic review and meta-analysis of vitamin B12 and GDM. As of September 22, 2021, 304 articles were searched in PubMed, Web of Science, EMBASE, and Cochrane databases, of which 15 studies met the inclusion criteria. Results presented there was no association between maternal vitamin B12 concentration during the first trimester with GDM, however, low vitamin B12 concentration in the second or third trimester of pregnancy was related to an increased risk of GDM. Compared with the non-GDM group, the vitamin B12 concentration in the GDM group was remarkably decreased (MD: -10·79; 95%CI: -21·37, -0·21), and vitamin B12 deficiency increased the risk for GDM (OR: 1·59; 95%CI: 1·10, 2·29). These effects were more significant among Asians. In addition, an increased ratio of high folate to low vitamin B12 in serum also increased the risk of GDM (OR: 1·87; 95% CI: 1·46, 2·41). These results suggest that more vitamin B12 may need to be provided during pregnancy.

Background: A developing fetus can be adversely affected by gestational diabetes mellitus (GDM). This condition is prevalent among South Asian women. A contributing factor to GDM is insulin resistance (IR). Only a few B12 and folate markers have been studied in association with GDM and IR, as studies have shown vitamin B12 (B12) and folate status to be associated with GDM. Objective: The current study aimed to determine the association between Vitamin B12 and folate markers and insulin resistance in pregnant women with GDM and NGT. Methods: Pakistani women (29 GDM and 41 NGT) with a mean age of 29 y, BMI, and gestational age of 33 weeks were included in the research. The serum total vitamin B12, and other parameters like folate, methylmalonic acid, plasma homocysteine and 5-methyl tetrachloro folic acid (RCF). The T-tests and chi-squared test and spearman's correlation test were used to determine whether there was any correlation between vitamin B12 and blood glucose levels in pregnant women with and without gestational diabetes. A simple multiple regression analysis was used to see whether B12 and folate status indicators predicted Insulin Resistance (IR). Results: There was no statistically significant difference between NGT and GDM, demonstrating that both groups have the same features. Although a significant difference was found between BMI (p=0.037), Serum Fasting Glucose (p=0.001), HOMA_IR (p=0.001), Serum HDL (p=0.001), Serum TC (p=0.040), and Systolic BP (p=0.001). Women in both groups took iron and folic acid supplements in roughly equal numbers. Still, the GDM group had an excess of women taking multivitamin supplements (P = 0.039) and women taking iron supplements (P=0.001). In Spearman’s analysis HOMA-IR correlated negatively with total serum B12 (P &lt; 0.00). The regression model is statistically significant with (F=1.927, P=0.046) p-value is less than the alpha value. Coefficient of determination R2=0,309, which indicated that 30.9% variation came in the response variable due to the explanatory variable and the rest due to other unknown factors. Practical implication Conclusions: it is concluded that there is a significant correlation between vitamin B12, folate and blood glucose level in Pakistani pregnant women in the third trimester. Moreover, vitamin B12 and folic acid have an impact on fetal health, i.e., weight, length and circumference of the head and chest. Keywords: gestational diabetes Mellitus, HOMA-IR, normal glucose tolerance, Peshawar

Associations of maternal serum folate, vitamin B12 and their imbalance with gestational diabetes mellitus: The mediation effects of the methionine cycle related metabolites.

Gestational diabetes mellitus (GDM) is described as a glucose intolerance of variable severity which begun or was firstly recognized during gravidity. Two major metabolic disorders, insulin resistance and β-cell dysfunction, currently play major role in pathogenesis of GDM. Our intention was to investigate total serum homocysteine and vitamin B12 levels in pregnant women with GDM and non-diabetic gravid women. Serum homocysteine and vitamin B12 levels were prospectively measured in a total of 79 pregnant women, 60 of whom were diagnosed with GDM, and 19 of whom were healthy controls. Serum homocysteine levels were analyzed by ELISA. Vitamin B12 concentrations were determined by chemiluminescent immunoassay, and lipids were determined enzymatically. GDM and control groups did not differ in terms of the serum homocysteine levels (median 7.24 vs 7.97 umol/L, respectively, p = 0.15). Nor did we find any association between serum homocysteine levels and BMI (r = 0.06, p = 0.55, respectively). There was no correlation between serum homocysteine and fasting serum glucose (r = 0.3, p = 0.8, respectively). There was no relationship between serum homocysteine concentrations and glycosylated hemoglobin (HgbA1c) levels (r = 0.06, p = 0.67, respectively). Serum vitamin B12 concentrations did not differ between the GDM and control groups (median 286 vs 262 pg/mL, respectively, p = 0.17). We found that levels of Vitamin B12 correlated inversely with fasting serum glucose concentrations (r = -0.44, p = 0.0009). Vitamin B12 concentrations increased along with LDL (r = 0.27, p = 0.043) and HDL (r = 0.38, p = 0.004) levels, however were inversely correlated with serum triglycerides (r = -0.34, p = 0.009). GDM patients with low Vitamin B12 values tend to have higher fasting serum glucose and altered lipid profiles (high triglycerides, low HDL and LDL). In women with GDM, serum homocysteine levels are not associated with HbA1c level, fasting glycemia, or BMI.

Micronutrients (folate and vitamin B12) and homocysteine are key components of the one-carbon metabolism and literature on the associations of these micronutrients with the pathophysiology of gestational diabetes mellitus (GDM) is unclear. The current study aims to examine the levels of these micronutrients across pregnancy in women who develop GDM and compare them with non-GDM women. A total of 200 pregnant women (100 Non-GDM and 100 GDM) were included in the study and blood samples were collected at 4 different time intervals throughout pregnancy (Visit-1 = 11-14 weeks, Visit-2 = 18-22 weeks, Visit-3 = 26-28 weeks, and Visit-4 = at delivery). Vitamin B12 levels at V3 and V4 (p = 0.031 and p = 0.001) and folate levels from V2, till delivery (p < 0.01 for V2, V3 and p = 0.025 for V4) were higher in GDM as compared to non-GDM. However, homocysteine levels were lower at all time points across gestation (p < 0.01 for all) in women with GDM. Intake of vitamin B12 & folate rich foods was comparable in GDM and Non-GDM women. Also, the percentage of GDM women who took vitamin B12 supplements was comparable between groups, while folate supplements were higher V1 (p < 0.01) in GDM women. Elevated micronutrients and lower homocysteine levels in GDM women necessitate more research for better understanding the role of these one carbon nutrients in the etiology of GDM and emphasizes the need to establish the optimum maternal vitamin B12 and folate levels for fetal development.

Objective: In this study, it was aimed to evaluate the nutritional adequacy status of pregnant women with gestational diabetes and to examine the relationship between biochemical parameters such as vitamin D, vitamin B12, hemoglobin, hematocrit and fasting glucose. Methods: In the study, serum vitamin D and B12 levels of 130 pregnant women between 24-28 weeks of gestation were examined. As a result of 75-gram oral glucose tolerance test, 70 pregnant women were diagnosed with gestational diabetes mellitus (GDM). The control group consisted of 60 healthy pregnant women. Nutritional factors were obtained through a questionnaire (anthropometric measurements, micronutrients, 3-day food consumption frequency, use of vitamin supplements) and groups were compared in terms of biochemical parameters (vitamin D, vitamin B12). Results: Pregnant women with GDM; mean age (30.34 ± 5.28), family history of diabetes (17.1%), pre-pregnancy body mass index percentage (54.3%), rate of skipping meals were higher. The rate of use of vitamin and mineral supplements in pregnant women with GDM was low. According to the analysis of 3-day food consumption records of pregnant women with GDM, it was determined that the intake of micronutrients vitamin D and vitamin B12 was insufficient. Biochemical parameters such as vitamin D, vitamin B12, hemoglobin and hematocrit were found to be lower in pregnant women with GDM. Conclusion: GDM is the most common endocrinological disorder in pregnancy. The study showed that inadequate nutrient intake negatively affects blood glucose levels and biochemical findings. Individuals with GDM should be referred to a nutritionist, medical nutrition therapy (TBT) appropriate for their individual characteristics should be given and monitored.

The insulin-like growth factor (IGF) axis is involved in the regulation of growth and metabolism; however, little is known about its role in the development of gestational diabetes mellitus (GDM). The aim of our study was to determine serum IGF-1, IGF-2 and selected IGF binding protein (IGFBP) levels and their mRNA expression in subcutaneous (SAT) and visceral adipose tissue (VAT) and placenta in the context of pregnancy and GDM. Thirty-seven pregnant females - 21 with GDM (GDM group) and 16 without GDM (P group) - and 15 age-matched non-pregnant control females (NP group) were included into the study. Blood samples were taken in 28th-32th and 36th-38th gestational week and 6-12 months after delivery (GDM and P group) or before diagnostic laparoscopy (NP group). SAT, VAT and placental samples were obtained during delivery or surgery, respectively. Compared with NP group serum IGF-1, IGFBP-1 and 3 were increased in both GDM and P subjects reaching maximum levels in 38th-39th gestational week. IGF-2 was elevated only in GDM group culminating 6 months after delivery (745.1±24.7 vs. 909.2±62.8 vs. 998.7±92.7 ng/ml, p=0.017 for GDM and 726.9±28.4 vs. 791.2±44.2 vs. 748.9±58.4 ng/ml, p=0.341 for P group, respectively). IGFBP-3 was higher and IGFBP-4 was decreased in GDM vs. P group during the whole study (IGFBP3: 631.0±22.9 vs. 536.9±15.4 ng/ml, p=0.003 for GDM vs. P group; IGFBP4: 14.79±2.71 vs. 22.78±2.94 ng/ml, p&amp;lt;0.001 for GDM vs. P group). mRNA expression of IGF-1, IGFBP-3, 4 and 5 was increased in SAT, while IGF-2 and IGFBP-4 mRNA was elevated in VAT in GDM and P relative to NP group. Placental mRNA expression of IGF-2, IGF-2 receptor, IGFBP-3 and 4 was higher in GDM compared with P group. In conclusion, females with GDM had increased serum IGF-2, IGFBP-3 and reduced IGFBP-4 levels and elevated placental mRNA expression of several components of IGF axis compared with pregnant women without GDM. These changes might play a role in the development of GDM. Disclosure K. Anderlová: None. P. Simjak: None. A. Cinkajzlova: None. J. Klouckova: None. H. Kratochvilova: None. Z. Lacinová: None. P. Kaválková: None. H. Krejci: None. M. Mraz: None. M. Haluzik: None. M. Krsek: None.

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.

Background:The estrogen receptor α (ERα) gene is a potential candidate gene of gestational diabetes mellitus (GDM). Objectives: The purpose of the study was to investigate the relationship of ERα gene polymorphism (single nucleotide polymorphism [SNP]) and its expression in placental tissues with the development of GDM. Methods: The SNPs of PvuII and Xba I in the ERα gene of 175 pregnant women with GDM and 240 healthy pregnant women were detected by polymerase chain reaction-restriction fragment length polymorphism. Immunohistochemistry and western blotting were used to analyze the expression of the ERα gene in placental tissues. Results: The results showed that the frequency of the CC + CT genotype and the C allele frequency of PvuII in the GDM group was significantly higher than that of the control group (p < 0.05). There was no significant difference in the genotype distribution and allele frequency of Xba I between the GDM group and control group. The expression of ERα in placental tissues of pregnant women with GDM was higher than that in the control group (p < 0.05). The participants with the PvuII CC + CT genotype had elevated levels of fasting blood glucose, homeostasis model assessment of insulin resistance (IR), and ERα expression in placental tissues compared with those with the TT genotype in the GDM group (p < 0.05). The SNP of Xba I of ERα gene had no correlation with clinical biochemical indicators of GDM and the expression of ERα in placental tissues (p > 0.05). Conclusions: This study suggested that SNP of the ERα gene and abnormal expression of ERα in placenta tissues were associated with GDM. The C allele of PvuII may be associated with GDM. In addition, SNP of the PvuII site in pregnant women with GDM was related to the degree of IR and to the upregulation of ERα expression in placental tissues, which may play an important role in the pathogenesis of GDM.

Background: Gestational diabetes mellitus (GDM) is one of the most common complications in pregnant women. Vitamin B12 serves in synthesis of methionine from homocysteine. Low vitamin B12 inhibits DNA synthesis and elevates homocysteine. Elevated homocysteine level linked with insulin resistance that is associated with GDM. Various researchers suggested an association of serum vitamin B12 concentration with GDM. Estimation of serum vitamin B12 may be helpful in management of GDM. Objective: To observe the association of vitamin B12 concentration with risk of developing GDM. Methods: This cross-sectional study was carried out at the Department of Laboratory Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh between March 2021 and February 2022. A total of 86 women were enrolled; of them 43 were GDM women selected as cases and 43 were normal pregnant women taken as control group. Their demographic profile, relevant medical history with clinical examination findings were recorded. Serum vitamin B12 concentrations of the study population were estimated following standard procedure. Results: The mean serum vitamin B12 concentration was found significantly low in GDM women (158.7±91.8 pmol/L versus 264.5±100.9 pmol/L, p= 0.001). Pearson’s correlation coefficient test between serum vitamin B12 concentration with fasting plasma glucose level, plasma glucose level 1 hours after 75 gm glucose and plasma glucose level 2 hours after 75 gm glucose showed a significantly negative correlation (r= -0.432, p= 0.004; r= -0.519, p&lt;0.001 and r= -0.687, p&lt;0.001). In multivariate logistic regression analysis, the odd ratio of vitamin B12 concentration with GDM was 1.997 (95% CI; p= 0.042). Conclusion: Serum vitamin B12 concentration is significantly low in GDM women, which is negatively correlated with plasma glucose levels among GDM women. Serum vitamin B12 concentration may be used as a predictive tool to identify risk of developing GDM.

The role of vitamin B12 in maternal obesity, insulin resistance, and gestational diabetesmellitus (GDM) is debatable. This study was undertaken to determine and compare the levels of serum vitamin B12 and homocysteine (Hcy) in pregnant women with and without GDM and to correlate them with maternal obesity. A total of 45 pregnant women with GDM and 45 pregnant women without GDM between 24 and 28 weeks of gestation were included in the study. Their body mass index (BMI) was calculated. Vitamin B12, Hcy, lipid profile, and blood glucose levels were measured. Serum vitamin B12 levels were low in both GDM and non-GDM groups. Only four women from the non-GDM group had normal vitamin B12 levels. Women with GDM had a significantly better socioeconomic status, probably accounting for relatively higher vitamin B12 levels, i.e., 146.2 pg/ml compared to 112 pg/ml in the non-GDM women.Women with GDM had significantly higher BMI (p = 0.001), higher triacylglycerol (TAG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), and lower high-density lipoprotein (HDL) as compared to non-GDM women. No significant statistical difference in Hcy was found between the two groups. Vitamin B12 levels were low in both groups of women, but were higher in the GDM group, probably because the higher socioeconomic status among women with GDM played a role.Vitamin B12 deficiency was linked with higher BMI, and women with GDM had higher levels of TAG, VLDL, and blood pressure, highlighting a state of insulin resistance.

NEK7-mediated activation of NLRP1 and NLRP3 inflammasomes in the progression of Gestational Diabetes Mellitus.