Evaluation of preadipocyte factor-1 (Pref-1) level in cord blood of newborns born by mothers with gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication, which leads to short and long-term consequences in both mother and fetus exposed to hyperglycemia. The aetiology of this condition is proposed to be based on the dysfunction of the adipose tissue, which is characterised by the aberrant generation of adipokines. One of them is preadipocyte factor-1 (Pref-1), which could mediate controlling the adaptation of the maternal metabolism to pregnancy. AIMS: The study aims to examine the level of Pref-1 in the cord blood of healthy pregnant women's neonates and fetuses born to mothers with GDM. MATERIALS AND METHODS: Cord blood samples were collected from 30 newborns of mothers with GDM and 40 newborns of healthy pregnant women. Pref-1 concentrations were measured with an ELISA kit. RESULTS: Fetal Pref-1 concentrations were significantly lower in newborns of mothers with GDM compared to the normal pregnancy group children (5.32 ± 0.29 vs. 7.38 ± 0.53; p < 0.001). Mothers with GDM had a significantly higher index of BMI before pregnancy, maternal gestational weight gain, and maternal fasting glucose. In-depth analysis through multiple variant linear regression revealed a significant association between fetal serum Pref-1 levels, exposure to GDM, and gestational age. CONCLUSION: These findings contribute valuable insights into maternal-fetal health and pave the way for more targeted and effective clinical interventions.

Butyrate and iso-butyrate: a new perspective on nutrition prevention of gestational diabetes mellitus.

BACKGROUND: Dietary imbalance, such as a lower proportion of complex carbohydrates and a higher protein diet, may contribute to gestational diabetes mellitus (GDM) risks through their metabolisms. However, there is a lack of knowledge regarding the association between butyrate, iso-butyrate, and GDM, which are metabolisms of the two primary nutrients above. This study aimed to clarify the association of butyrate and iso-butyrate with GDM. METHODS: A nested case-control study was conducted based on the Beijing Birth Cohort Study (BBCS) from 2017 to 2018. Totally, 99 singleton women were involved (GDM: n = 49, control: n = 50). All participants provided blood samples twice (in their first and second trimesters). Gas chromatography-mass spectrometry (GC-MS) was used for butyrate and iso-butyrate detection. Unconditional logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. RESULTS: The results showed that butyrate in the first trimester was negatively correlated with GDM (odds ratio (OR): 0.00, 95% confidential interval (CI): 0.00-0.21, P = 0.008), and iso-butyrate in the second trimester was positively related to GDM (OR: 627.68, 95% CI: 40.51-9724.56, P < 0.001). The ratio (butyrate/iso-butyrate) was negatively associated with GDM, both in the first trimester (OR: 0.00, 95%CI: 0.00-0.05, P < 0.001) and in the second trimester (OR: 0.52, 95% CI: 0.34-0.80, P = 0.003). The area under the curve (AUC) using the ratio in the first trimester combined with clinical risk factors achieved 0.89 (95% CI: 0.83-0.95). Iso-butyrate in the second trimester combined with clinical risk factors achieved an AUC of 0.97 (95% CI: 0.92-1.00). CONCLUSIONS: High iso-butyrate and low butyrate levels may be associated with an increased risk of GDM. As they are produced through dietary nutrient formation by gut microbiota, further studies on the association of dietary intake and butyrate or iso-butyrate concentration in plasma may help find a novel approach to nutritional intervention for GDM.

The application of plasma circRAD18 in the prediction of gestational diabetes mellitus (GDM) and its adverse effects.

BACKGROUND: In cancer biology, circRAD18 promotes glucose metabolism, potentially indicating its involvement in glucose metabolism-related disorders, such as gestational diabetes mellitus (GDM). The present study investigated the predictive role of circRAD18 in GDM and its potential adverse effects. METHODS: A total of 482 women who intended to get pregnant in short-term were enrolled. For those who successfully conceived, plasma samples were collected and followed up until delivery to monitor the occurrence of GDM and its associated adverse events. The accumulation of circRAD18 in plasma was analyzed using RT-qPCR. GDM-free curves and ROC curves were plotted to assess the predictive value of plasma circRAD18 for GDM. RESULTS: After admitting 482 female patients, 388 of them achieved pregnancy within half a year. During the follow-up period, 52 cases were diagnosed with GDM. Compared to non-GDM group (n = 336), the GDM group (n = 52) had a lower accumulation level of circRAD18 on the day of pregnancy confirmation. In addition, low levels of circRAD18 accumulation on that day distinguished potential GDM patients from non-GDM cases. The 388 cases were divided into high and low circRAD18 level groups (n = 194). GDM-free curve analysis showed that patients in the low circRAD18 level group had a higher incidence of GDM compared to the high level group (43/194 vs. 9/194). A close association was found between low levels of plasma circRAD18 and hypertension, but not premature delivery, intrauterine death, malformation, intrauterine infection, miscarriage, macrosomia or intrauterine distress. CONCLUSION: The reduction in the accumulation of plasma circRAD18 is predictive of GDM and hypertension in pregnant women.

Association of DPP-4 Concentrations with the Occurrence of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain.

Gestational diabetes mellitus (GDM) is considered one of the most common diseases that occur during pregnancy. In addition to increasing the risk of numerous complications throughout gestation, it is also believed to have a long-term potential to impact the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease for the mother and her offspring. While there are clear guidelines for healthy weight gain in pregnancy depending on pre-pregnancy BMI, as well as dietary and training recommendations to achieve this, an increasing number of women are experiencing excessive gestational weight gain (EGWG). Such patients have a higher risk of developing GDM and gestational hypertension, as well as requiring caesarian delivery. Dipeptidyl peptidase-4 (DPP-4) is a glycoprotein that seems to play an important role in glucose metabolism, and inhibition of its activity positively affects glucose regulation. The aim of our study was to compare DPP-4 concentrations in patients with GDM and EGWG with healthy women. DPP-4 levels were assessed in serum and urine samples collected on the day of delivery. The bioelectrical impedance analysis (BIA) method was also used to analyze the body composition of patients on the second day of the postpartum period. DPP-4 serum concentrations were significantly higher in patients in the GDM and EGWG groups compared to healthy women. Urinary DPP-4 concentrations were significantly higher in the control and GDM groups than in the EGWG group. Serum DPP-4 levels were positively correlated with BMI measured before pregnancy, on the delivery day, and in the early postpartum period, among other factors. According to our knowledge, this is the first study to determine DPP-4 levels in EGWG patients. DPP-4 may be related to the occurrence of GDM and EGWG; however, this requires further research.

Effect of different nutrients on blood glucose, inflammatory response and oxidative stress in gestational diabetes mellitus: a network meta-analysis.

We searched PubMed, Web of Science, Embase, The Cochrane Library, China Biomedical Literature Database and other databases from inception to June 2023. The included studies were randomised controlled trials (RCT). The studies were screened by four authors, divided into two independent pairs. A total of eighteen studies were included, including 1362 patients, involving twelve intervention measures. The different nutrients had a significant effect on improving blood glucose, reducing inflammation levels and reducing oxidative stress compared with placebo (P < 0.05). Cumulative probability ranking showed that vitamin A + vitamin D + vitamin E ranked first in lowering fasting blood glucose (standardised mean difference (SMD) = 41.30, 95 % CI (2.07, 825.60)) and postprandial 2-h blood glucose (SMD = 15.19, 95 % CI (4.16, 55.53)). In terms of insulin resistance index, the first highest probability ranking is vitamin D (SMD = 5.12, 95 % CI (0.76, 34.54)). In terms of reducing the high-sensitivity C-reactive protein level, the first in probability ranking is VE (SMD = 2.58, 95 % CI (1.87,3.55)). The results of cumulative probability ranking showed that Mg + Zn + Ca + VD ranked first in reducing TNF-α (SMD = 1.90, 95% CI (0.40, 9.08)) and IL-6 (SMD = 1.83, 95 % CI (0.37, 9.12)). In terms of reducing malondialdehyde levels, the first ranked probability is VB1 (SMD = 4.99, 95 % CI (1.85, 13.46)). Cumulative probability ranking results showed that Ca + VD ranked first in reducing total antioxidant capacity (SMD = 0.66,95 % CI (0.38, 1.15)) and glutathione (SMD = 1.39, 95 % CI (0.43, 4.56)). In conclusion, nutritional interventions have significant effects on improving blood glucose, inflammatory levels and oxidative stress in patients with gestational diabetes. Due to the high uncertainty in the results and differences in the number and quality of studies included, the reliability of the conclusions still needs to be validated by conducting large-sample, high-quality RCT studies.

Predicting insulin use among women with gestational diabetes diagnosed in oral glucose tolerance test.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications affecting pregnant women. While most women will achieve adequate glycemic levels with diet and exercise, some will require pharmacological treatment to reach and maintain glucose levels between the desired thresholds. Identifying these patients early in pregnancy could help direct resources and interventions. METHODS: This retrospective cohort of women with GDM diagnosed with an abnormal 75g-OGTT presents data from 869 patients (724 in the diet group and 145 in the insulin group). Univariate logistic regression was used to compare the groups, and multivariable logistic regression was used to identify independent factors associated with the need for insulin. A log-linear function was used to estimate the probability of requiring pharmacological treatment. RESULTS: Women in the insulin group had higher pre-pregnancy BMI index (29.8 vs 27.8 kg/m2, odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.09), more frequent history of previous GDM (19.4% vs. 7.8%, OR 2.84, 95% CI 1.59-5.05), were more likely to have chronic hypertension (31.7% vs. 23.2%, OR 1.54, 95% CI 1.04-2.27), and had higher glucose levels at all three OGTT points. Multivariable logistic regression final model included age, BMI, previous GDM status, and the three OGTT values as predictors of insulin requirement. CONCLUSIONS: We can use regularly collected data from patients (age, BMI, previous GDM status, and the three OGTT values) to calculate the risk of a woman with GDM diagnosed in OGTT needing insulin. Identifying patients with a greater risk of requiring pharmacological treatment could help healthcare services to better allocate resources and offer closer follow-up to high-risk patients.

Adropin as a potential protective factor of metabolic complications in obese pregnant women with hyperglycaemia diagnosed in early pregnancy.

Adropin is a hormone which increases insulin sensitivity. It enhances the oxygenation of glucose in the muscles. The 91 obese pregnant women (BMI >30 kg/m2) with gestational diabetes mellitus (GDM) diagnosed in the first half of pregnancy has been recruited to the study group. The control group consisted of 10 age matched and homogeneous pregnant women with BMI <25 kg/m2. Blood samples were collected on visit V1 - between the 28th and 32nd week and on visit V2 - between the 37th and 39th week of gestation. The ELISA test was used to measure the adropin level. The results in the study group and the control group were compared. Blood samples were collected at the same visits. The median concentration of adropin was 442.2 pg/ml on V1 and 453.1 pg/ml on V2. The increase was significant (p<0.05). Results were significantly lower in the control group's patients, i.e. 57.0 pg/ml (p<0.001) on V1 and 107.9 pg/ml on V2 (p<0.001). The higher adropin level on the V1 and V2 visits were related to patients' lower BMI and better metabolic control. The increase in the adropin level in the third trimester may have been involved in the weight gain reduction, whereas better dietary adherence might have had a compensatory effect on increasing insulin resistance. However, the small control group is a limitation of this study.

Serum folate mediates the associations of MTHFR rs1801133 polymorphism with blood glucose levels and gestational diabetes mellitus in Chinese Han pregnant women.

This study aimed to explore the mediation effects of one-carbon metabolism (OCM) related nutrients on the association between MTHFR rs1801133 polymorphism and gestational diabetes mellitus (GDM). Folate, vitamin B12 and homocysteine (Hcy) were measured in the serum of 1254 pregnant women. Linear and logistic regressions were used to estimate the associations of OCM nutrients and MTHFR rs1801133 polymorphism with blood glucose levels and GDM risk. Mediation analysis was applied to test the mediation effects of folate, vitamin B12 and Hcy on the association of MTHFR rs1801133 polymorphism with blood glucose concentrations and GDM. Pregnant women with MTHFR rs1801133 CC genotype had higher serum folate (10·75 v. 8·90 and 9·40 ng/ml) and lower serum Hcy (4·84 v. 4·93 and 5·20 µmol/l) than those with CT and TT genotypes. Folate concentrations were positively associated with fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG), 2-h plasma glucose (2-h PG) and GDM risk. Vitamin B12 levels were negatively correlated with FPG and GDM. Although no direct association was found between MTHFR rs1801133 genotypes and GDM, there were significant indirect effects of MTHFR rs1801133 CC genotype on FPG (ß: 0·005; 95 % CI: 0·001, 0·013), 1-h PG (ß: 0·006; 95 % CI: 0·001, 0·014), 2-h PG (ß: 0·007; 95 % CI: 0·001, 0·015) and GDM (ß: 0·006; 95 % CI: 0·001, 0·014) via folate. In conclusion, serum folate mediates the effect of MTHFR rs1801133 on blood glucose levels and GDM. Our findings potentially provide a feasible GDM prevention strategy via individualised folate supplementation according to the MTHFR genotypes.

The effect of fruit consumption time on glucose regulation in pregnancy with gestational diabetes / O efeito do tempo de consumo de fruta na regulação da glicose na gravidez com diabetes gestacional

ABSTRACT Objective This study aims to determine the effect of fruit consumption time on blood glucose regulation in pregnant women with gestational diabetes. Methods The study was carried out with 64 volunteer participants diagnosed with gestational diabetes. Participants who were directed to the Department of Nutrition and Dietetics were divided into two groups according to the order of application; Group 1 was included in the nutrition treatment program for a week, consuming fruit for the main meal and Group 2 for the snack. During this process, the participants were applied a personalized nutrition plan that was adjusted equally for macronutrients of all meals containing isocaloric 3 main and 4 snacks. In this process, blood glucose values were measured six times a day by the participants and the blood glucose results of both groups before starting the nutrition therapy and on the seventh day after starting the medical nutrition therapy were compared. Results The mean age of the women participating in the study was 33.50±4.95 years and 32.28±5.18 years for the 1st and 2nd groups, respectively, and the groups were similar in terms of anthropometric measurements. The post-diet average of postprandial blood glucose levels in the morning within each group dropped from 180mg/d to 115mg/dL (p<0,001) for Group 1 and from 185mg/dL to 110mg/dL (p<0,001) for Group 2. There was a decrease in the fasting plasma glucose and postprandial blood glucose levels measured in the morning, noon and evening before and after the medical nutrition therapy of the groups, but no statistically significant difference was found between the groups (p>0.05). All participants on the gestational diabetes diet had normal blood sugar levels without the need for insulin. A statistically significant decrease was observed in the postprandial blood glucose-fasting plasma glucose difference levels of the pregnant women in the group that consumed fruit for snacks (Group 2) on the seventh day of the study (p<0,001). There was no significant difference in the pre-diet and post-diet morning fasting plasma glucose values of both groups (p>0,05). Conclusion This study found that medical nutrition therapy in pregnant women with gestational diabetes led to a decrease in blood glucose levels, but consuming fruits as a snack or at the main meal did not make a significant difference on fasting plasma glucose and postprandial blood glucose. It was concluded that the type and amount of carbohydrates consumed daily in gestational diabetes are determinative on blood glucose level.

RESUMO Objetivo O objetivo deste estudo é determinar o efeito do tempo de consumo de fruta na regulação da glucose no sangue em mulheres grávidas com diabetes gestacional. Métodos Este estudo foi realizado com 64 participantes voluntários diagnosticados com diabetes gestacional. Os participantes que foram encaminhados para o Departamento de Nutrição e Dietética foram divididos em dois grupos, de acordo com a ordem da sua aplicação. O grupo 1 foi incluído no programa de tratamento médico nutricional durante uma semana, consumindo fruta para a refeição principal e o grupo 2 para os lanches. Neste processo, foi aplicado aos participantes um plano de nutrição personalizado, com isocalórico, 3 refeições principais e 4 lanches, os macronutrientes de todas as refeições foram ajustados igualmente. Neste processo, os valores de glicemia foram medidos seis vezes por dia pelos participantes, e foram comparados os resultados da glicemia de ambos os grupos antes de se iniciar a terapia nutricional médica e no sétimo dia após o início da terapia nutricional médica. Resultados A idade média das mulheres que participaram no estudo foi de 33,50±4,95 e 32,28±5,18 anos para o 1º e 2º grupos, respetivamente, e não houve diferença entre os grupos em termos de medidas antropométricas. A glicemia média pós-prandial de manhã após terapia nutricional médica dentro dos grupos variou entre 180mg/d a 115mg/dL (p<0,001) para o Grupo 1, e de 185mg/dL a 110mg/dL para o Grupo 2 (p<0,001). Houve uma diminuição nos níveis de glicemia em jejum e glicemia média pós-prandial medidos de manhã, meio-dia e noite antes e depois da terapia nutricional médica dos grupos, mas não houve diferença estatisticamente significativa entre os grupos (p>0,05). Os níveis de açúcar no sangue de todos os participantes na dieta diabetes gestacional baixaram para níveis normais sem necessidade de terapia com insulina. Uma diminuição estatisticamente significativa foi observada no sétimo dia do estudo nos níveis de diferença do glicemia média pós-prandial-glicemia em jejum das mulheres grávidas do grupo que consumiram fruta como aperitivo (Grupo 2). (p<0.001). Não houve diferença significativa nos valores de glicemia em jejum matinal de ambos os grupos antes e depois da dieta (p>0,05). Conclusão Como resultado deste estudo, verificou-se que a terapia nutricional levou a uma diminuição do açúcar no sangue em mulheres grávidas com diabetes gestacional, mas o consumo de fruta como lanche ou refeição principal não fez uma diferença significativa no jejum e na glucose do sangue pós-prandial. Concluiu-se que o tipo e a quantidade de hidratos de carbono consumidos diariamente na diabetes gestacional são determinantes para o nível de glicose no sangue.

Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of gestational diabetes mellitus.

Objective: Gestational diabetes mellitus (GDM) has adverse effects on the health of mothers and their offspring. Currently, no known biomarker has been proven to have sufficient validity for the prediction of GDM in the first trimester of pregnancy. The aim of this study was to investigate the potential relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) levels in the first trimester of pregnancy and later GDM risk and to evaluate the performance of serum NGAL as a biomarker for the prediction of GDM. Methods: The study was conducted by recruiting participants at 8-13 weeks of gestation from The First Affiliated Hospital of Chengdu Medical College between January and June 2021; participants were followed up for oral glucose tolerance test (OGTT) screening at 24-28 gestational weeks. We examined the serum NGAL levels of all subjects in the first trimester who met the inclusion and exclusion criteria. Anthropometric, clinical, and laboratory parameters of the study subjects were obtained during the same study period. A logistic regression model was carried out to investigate the potential relationship between serum NGAL levels in the first trimester of pregnancy and later GDM risk. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the discrimination and calibration of serum NGAL as a biomarker for the prediction of GDM in the first trimester of pregnancy. Results: Serum NGAL levels in the first trimester of pregnancy were significantly higher in women who later developed GDM than in those who did not develop GDM. Serum NGAL levels in the first trimester of pregnancy were positively associated with an increased risk of GDM after adjustment for potential confounding factors. The risk prediction model for GDM constructed by using serum NGAL levels in the first trimester of pregnancy achieved excellent performance. Conclusions: Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of GDM, which could help guide the clinical practice of antenatal care.

Lower versus Higher Glycemic Criteria for Diagnosis of Gestational Diabetes.

BACKGROUND: Treatment of gestational diabetes improves maternal and infant health, although diagnostic criteria remain unclear. METHODS: We randomly assigned women at 24 to 32 weeks' gestation in a 1:1 ratio to be evaluated for gestational diabetes with the use of lower or higher glycemic criteria for diagnosis. The lower glycemic criterion was a fasting plasma glucose level of at least 92 mg per deciliter (≥5.1 mmol per liter), a 1-hour level of at least 180 mg per deciliter (≥10.0 mmol per liter), or a 2-hour level of at least 153 mg per deciliter (≥8.5 mmol per liter). The higher glycemic criterion was a fasting plasma glucose level of at least 99 mg per deciliter (≥5.5 mmol per liter) or a 2-hour level of at least 162 mg per deciliter (≥9.0 mmol per liter). The primary outcome was the birth of an infant who was large for gestational age (defined as a birth weight above the 90th percentile according to Fenton-World Health Organization standards). Secondary outcomes were maternal and infant health. RESULTS: A total of 4061 women underwent randomization. Gestational diabetes was diagnosed in 310 of 2022 women (15.3%) in the lower-glycemic-criteria group and in 124 of 2039 women (6.1%) in the higher-glycemic-criteria group. Among 2019 infants born to women in the lower-glycemic-criteria group, 178 (8.8%) were large for gestational age, and among 2031 infants born to women in the higher-glycemic-criteria group, 181 (8.9%) were large for gestational age (adjusted relative risk, 0.98; 95% confidence interval, 0.80 to 1.19; P = 0.82). Induction of labor, use of health services, use of pharmacologic agents, and neonatal hypoglycemia were more common in the lower-glycemic-criteria group than in the higher-glycemic-criteria group. The results for the other secondary outcomes were similar in the two trial groups, and there were no substantial between-group differences in adverse events. Among the women in both groups who had glucose test results that fell between the lower and higher glycemic criteria, those who were treated for gestational diabetes (195 women), as compared with those who were not (178 women), had maternal and infant health benefits, including fewer large-for-gestational-age infants. CONCLUSIONS: The use of lower glycemic criteria for the diagnosis of gestational diabetes did not result in a lower risk of a large-for-gestational-age infant than the use of higher glycemic criteria. (Funded by the Health Research Council of New Zealand and others; GEMS Australian New Zealand Clinical Trials Registry number, ACTRN12615000290594.).

[Effects of gestational weight on the association between serum high sensitivity C reaction protein and gestational diabetes mellitus among twin gestations: A cohort study].

OBJECTIVE: To investigate the association between serum high sensitivity C-reaction protein (hsCRP) in early pregnancy and gestational diabetes mellitus (GDM) among twin pregnant women, and to explore the effects of the pre-pregnant body mass index (BMI) and gestational weight gain (GWG) status on such association. METHODS: Twin pregnant women with pre-pregnant BMI greater than or equal to 18.5 kg/m2 were recruited at Department of Obstetrics and Gynecology of Peking University Third Hospital from March 2017 to December 2020. Serum samples collected in early pregnancy were analyzed for hsCRP using particle-enhanced immunoturbidimetric method. In the following visits, the information about GWG and GDM were prospectively collected in every trimester. The association effect between hsCRP tertiles and GDM were estimated using Logistic regression, and further converted into risk ratio (RR). Cochran-Mantel-Haenszel test and mediation analysis were used to explore the effects of BMI and GWG status on the association. RESULTS: Among the included 570 twin pregnant women, 31.6% deve-loped GDM, 26.1% were pre-pregnant overweight or obesity, and 49.5% with GWG out of referenced range. After adjustment for confounding factors, risk of developing GDM in twin gestations with the middle tertile and highest tertile of serum hsCRP in early pregnancy were 1.42 fold (95%CI: 1.02-1.89) and 1.54 fold (95%CI: 1.12-2.02), respectively, compared with the lowest tertile of serum hsCRP, and there existed significantly linear trend (P=0.022). Findings from mediation analysis illustrated that pre-pregnant BMI had partial mediating effect on the association, and BMI accounted for 23.84% (P < 0.001) of the increasing GDM risks with elevated hsCRP. Joint analysis with hsCRP and GWG found that those who were with GWG out of referenced range accompanied with the higher hsCRP tertiles (>1.21 mg/L) had significantly 2.31 fold increased risk according to those who were with GWG in the referenced range accompanied with the lowest hsCRP tertile (≤1.21 mg/L, P < 0.01). CONCLUSION: Elevated hsCRP in early pregnancy significantly increased GDM risk among twin pregnant women. The hsCRP-GDM association was dependent on GWG status, and pre-pregnant BMI had partial mediating effect on such association. It is suggested that twin pregnant women should consider systemic inflammation and gestational weight at the same time to reduce GDM risk.

Study of serum miR-518 and its correlation with inflammatory factors in patients with gestational diabetes mellitus complicated with hypertensive disorder complicating pregnancy.

OBJECTIVE: Gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) are common complications during pregnancy. This study estimated the correlation of serum miR-518 and inflammatory factors in GDM complicated with HDCP patients (GDM&HDCP). METHODS: Total 240 pregnant women were enrolled, including 118 cases with GDM alone, 57 cases with GDM&HDCP, and 65 healthy pregnant women. The expressions of serum miR-518 and PPARα were detected by RT-qPCR. The clinical diagnostic efficacy of miR-518 for GDM and GDM&HDCP was analyzed via ROC curve. Pearson coefficient was used to analyze the correlation between miR-518 and serum inflammatory factors (hs-CRP, IL-6, and TNF-α), and the relevance between peroxisome proliferator-activated receptor α (PPARα) and serum inflammatory factors. The targeted binding of miR-518 and PPARα was verified using dual-luciferase assay. RESULTS: Serum miR-518 was highly-expressed in GDM and GDM&HDCP patients, but far higher in GDM&HDCP patients. Serum miR-518 level > 1.815 could assist the diagnosis of GDM (81.53% sensitivity and 100% specificity). Serum miR-518 expression was positively-correlated with serum inflammatory factors. miR-518 targeted PPARα and PPARα was lowly-expressed in the serum of GDM and GDM&HDCP patients. PPARα was negatively-linked with serum inflammatory factors. CONCLUSION: High expression of miR-518 assists the diagnosis of GDM and GDM&HDCP, and miR-518 regulates the serum inflammatory factors by inhibiting PPARα.

Association of surfactant protein D gene polymorphism with susceptibility to gestational diabetes mellitus: a case-control study.

BACKGROUND: Surfactant protein D (SP-D) is a critical component of the innate immune system intrinsically linked to energy metabolism. However, the relationship of SP-D gene polymorphisms and gestational diabetes mellitus (GDM) remains unclear. In this study, we analyzed SP-D gene polymorphisms in GDM patients and nondiabetic controls and then determined the association of SP-D gene polymorphisms with GDM. METHODS: We examined a common genetic polymorphism located in the SP-D coding region (rs721917, Met31Thr) in GDM patients (n = 147) and healthy pregnant controls (n = 97) by using a cleaved amplification polymorphism sequence-tagged sites (PCR-RFLP) technique. The level of SP-D protein in the serum of GDM patients and nondiabetic controls was determined by ELISA. The gene and allele frequencies of SP-D and their association with GDM as well as SP-D protein levels were analyzed and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: We found that there was a significant association of the SP-D polymorphism (rs721917) with GDM. The SP-D (T/T) genotype was found in 11.6% and 21.6% of GDM patients and matched healthy controls, respectively (odds ratio, 0.473; 95% confidence interval, 0.235-0.952; P = 0.033), indicating that women with the (T/T) genotype had a lower prevalence of GDM (OR = 0.473). Women with the T/C genotype showed an increased risk of GDM (odds ratio, 2.440; 95% confidence interval, 1.162-5.123; P = 0.017). We did not observe corrections between glucose homeostasis markers and SP-D genotypes in women with GDM. Furthermore, serum SP-D levels were higher in GDM patients than in matched healthy controls. CONCLUSIONS: This study found the first evidence that an SP-D gene polymorphism (rs721917) was associated with GDM, which may provide the basis for further study on how SP-D plays a regulatory role in GDM.

The effects of gestational diabetes mellitus with maternal age between 35 and 40 years on the metabolite profiles of plasma and urine.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35-40 years at early and late gestation. METHODS: Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). RESULTS: One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. CONCLUSION: This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35-40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.

Higher hemoglobin levels are an independent risk factor for gestational diabetes.

Incidence of gestational diabetes (GDM) has increased rapidly. It poses significant risks for both mother and fetus affecting also negatively their longer-term metabolic heath. We asked whether early pregnancy maternal hemoglobin (Hb) levels, indicative for tissue oxygenation, would affect mother's metabolic health and fetal outcome. We assessed in FinnGeDi, a Finnish multicenter case-control study for GDM (n = 1828), association of maternal 1st trimester Hb levels with metabolic parameters and perinatal outcome. Our data show that mothers with GDM had higher Hb levels compared to controls (mean difference 1.746 g/L). Hb levels associated positively with pre-pregnancy body mass index (BMI), fasting glucose levels and glucose levels in a glucose tolerance test and systolic and diastolic blood pressure (bp) levels. When assessed in quartiles the highest Hb quartile had more chronic and gestational hypertension and the most adverse outcome of the metabolic parameters, dose-dependency seen in bp, BMI and glucose levels. In a multivariable regression analysis Hb levels remained an independently associated parameter for GDM after adjusting for key covariates (OR 1.019, 95% CI [1.007; 1.031]). In conclusion, higher maternal Hb levels within the normal variation are an independent risk factor for GDM in this population but have little effect on perinatal outcome.

Effectiveness of carbohydrate counting and Dietary Approach to Stop Hypertension dietary intervention on managing Gestational Diabetes Mellitus among pregnant women who used metformin: A randomized controlled clinical trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complication of pregnancy that has significant impacts on both mother and her offspring health. The present study aimed to examine the effect of carbohydrate counting, carbohydrate counting combined with DASH, and control dietary interventions on glycemic control, and maternal and neonatal outcomes. METHODS: A total of 75 pregnant women with GDM at 24th - 30th week of gestation were enrolled and randomized to follow one of the three diets: control or carbohydrate counting, or carbohydrate counting combined with Dietary Approach to Stop Hypertension (DASH). Only 70 of them completed the study until delivery. Fasting blood samples were taken at baseline and the end of the study to measure fasting blood glucose (FBG), fasting insulin, glycated hemoglobin (HbA1c), and fructosamine. Homeostatic model assessment-insulin resistance (HOMA-IR) score was calculated using HOMA2 calculator program. The participants recorded at least four blood glucose readings per day. Maternal and neonatal outcomes were collected from medical records. Dietary intake was assessed by three-day food records at the baseline and the end of the study. RESULTS: Adherence to the three dietary interventions, resulted in decreased FBG levels significantly among all the participants (P < 0.05). Consumption of the carbohydrate counting combined with the DASH diet showed significant reduction in serum insulin levels and HOMA-IR score compared to carbohydrate counting group and control group. Means of fructosamine and HbA1c did not differ significantly among the three intervention diet groups. Overall mean of 1-h postprandial glucose (1 h PG) level was significantly lower in the carbohydrate counting combined with DASH group compared with that in the carbohydrate counting group and the control group (P < 0.001). The number of women who were required to commence insulin therapy after dietary intervention was significantly lower in carbohydrate counting group and carbohydrate counting combined with DASH group (P = 0.026). There were no significant differences in other maternal and neonatal outcomes among the three dietary intervention groups. CONCLUSIONS: The carbohydrate counting and the carbohydrate counting combined with DASH dietary interventions resulted in beneficial effects on FBG and 1 h PG compared with the control diet. The three dietary interventions produced similar maternal and neonatal outcomes in women with GDM. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov under the identification code: NCT03244579. https://clinicaltrials.gov/ct2/show/NCT03244579.

Study on the Effects of Individualized Nutritional Intervention on Pregnancy Outcome and Neonatal Immune Function in Patients with Gestational Diabetes Mellitus.

OBJECTIVE: To study the effects of individualized nutritional intervention on pregnancy outcome and neonatal immune function in patients with gestational diabetes mellitus (GDM). METHODS: A retrospective analysis was conducted on 100 GDM patients from the obstetrics and gynecology department of our institute between February 2019 and February 2020. The patients were allocated into the control group given regular intervention and the experimental group given individualized nutritional intervention according to different intervention measures, with 50 cases in each group. The comparison was carried out for patients in the two groups with regard to their modality of delivery, neonatal health, their plasma glucose in fasting state, 2 h after eating, and before bedtime; glycohemoglobin at 8 months of pregnancy, at 9 months of pregnancy, during labor, and 1 month after delivery; their complications; and neonatal CD3+, CD4+, and CD8+ levels. RESULTS: The experimental group outperformed the control group in terms of the spontaneous delivery rate, the number of healthy neonates, and neonatal CD3+, CD4+, and CD8+ levels (P < 0.05). The plasma glucose in fasting state, 2 h after eating, and before bedtime; the glycohemoglobin at 8 months of pregnancy, at 9 months of pregnancy, during labor, and 1 month after delivery; and the incidence of complications of the experimental group were significantly lower than those of the control group (P < 0.05). CONCLUSION: Individualized nutritional intervention increases the rate of spontaneous delivery in GDM patients, enhances neonatal immune function, stabilizes plasma glucose, and reduces complications.