RESUMEN
BACKGROUND: Observational studies have revealed associations between maternal lipid metabolites and gestational diabetes mellitus (GDM). However, whether these associations are causal remain uncertain. OBJECTIVE: To evaluate the causal relationship between lipid metabolites and GDM. METHODS: A two-sample Mendelian randomization (MR) analysis was performed based on summary statistics. Sensitivity analyses, validation analyses and reverse MR analyses were conducted to assess the robustness of the MR results. Additionally, a phenome-wide MR (Phe-MR) analysis was performed to evaluate potential side effects of the targeted lipid metabolites. RESULTS: A total of 295 lipid metabolites were included in this study, 29 of them had three or more instrumental variables (IVs) suitable for sensitivity analyses. The ratio of triglycerides to phosphoglycerides (TG_by_PG) was identified as a potential causal biomarker for GDM (inverse variance weighted (IVW) estimate: odds ratio (OR) = 2.147, 95% confidential interval (95% CI) 1.415-3.257, P = 3.26e-4), which was confirmed by validation and reverse MR results. Two other lipid metabolites, palmitoyl sphingomyelin (d18:1/16:0) (PSM(d18:1/16:0)) (IVW estimate: OR = 0.747, 95% CI 0.583-0.956, P = 0.021) and triglycerides in very small very low-density lipoprotein (XS_VLDL_TG) (IVW estimate: OR = 2.948, 95% CI 1.197-5.215, P = 0.015), were identified as suggestive potential biomarkers for GDM using a conventional cut-off P-value of 0.05. Phe-MR results indicated that lowering TG_by_PG had detrimental effects on two diseases but advantageous effects on the other 13 diseases. CONCLUSION: Genetically predicted elevated TG_by_PG are causally associated with an increased risk of GDM. Side-effect profiles indicate that TG_by_PG might be a target for GDM prevention, though caution is advised due to potential adverse effects on other conditions.
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Biomarcadores , Diabetes Gestacional , Lipidómica , Lípidos , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Femenino , Embarazo , Factores de Riesgo , Lípidos/sangre , Medición de Riesgo , Biomarcadores/sangre , Fenotipo , Predisposición Genética a la Enfermedad , Reproducibilidad de los Resultados , FenómicaRESUMEN
Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28-45 kg/m2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM.
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Glucemia , Índice de Masa Corporal , Prueba de Tolerancia a la Glucosa , Homeostasis , Obesidad , Sobrepeso , Humanos , Femenino , Embarazo , Adulto , Glucemia/metabolismo , Obesidad/metabolismo , Obesidad/sangre , Sobrepeso/metabolismo , Sobrepeso/sangre , Diabetes Gestacional/metabolismo , Diabetes Gestacional/sangre , Recién Nacido , Preescolar , Insulina/sangre , Insulina/metabolismo , Péptido C/sangre , Ayuno/sangre , Complicaciones del Embarazo/metabolismo , Complicaciones del Embarazo/sangreRESUMEN
BACKGROUND: This study aimed to investigate the effects of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-hours postprandial blood glucose (2hPBG), and fasting insulin (FINS) levels on pregnancy outcomes and their predictive value in patients with gestational diabetes mellitus (GDM). METHODS: A total of 109 pregnant women with GDM (GDM group) were included and assayed for serum FBG, 2hPBG, HbA1c, and FINS levels. The incidence of adverse pregnancy outcomes was recorded. GDM patients were divided into the poor pregnancy outcome group and the favorable pregnancy outcome group and analyzed for HbA1c, FBG, 2hPBG, and FINS. The predictive value of serum index combined detection on GDM pregnancy outcome was assessed, and the effect of serum indices on pregnancy outcome was evaluated in GDM patients with logistic regression. RESULTS: In the GDM group, there were 8 cases of premature membranes breaking (7.34%), 6 cases of premature delivery (5.50%), 3 cases of hyperamniotic fluid (2.75%), 2 cases of neonatal asphyxia (1.83%), 5 cases of fetal growth restriction (4.59%), and 3 cases of low-birth-weight infants (2.75%). The total incidence of adverse preg-nancy outcomes was 24.77% (27/109). HbA1c, FBG, 2hPBG, and FINS in the poor pregnancy outcome group were higher than those in the favorable pregnancy outcome group. The AUC value of blood biochemical indicators combined detection in predicting pregnancy outcome in GDM patients was higher than of HbA1c, FBG, 2hPBG, and FINS alone detection. HbA1c ≥ 6.94%, FBG ≥ 7.18 mmol/L, 2hPBG ≥ 9.36 mmol/L, and FINS ≥ 13.07 U/L were the risk factors affecting pregnancy outcomes in GDM patients. CONCLUSIONS: The changes of HbA1c, FBG, 2hPBG, and FINS levels in GDM patients are associated with adverse pregnancy outcomes, and the combined detection of serum indicators has predictive value for pregnancy outcomes in GDM patients.
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Glucemia , Diabetes Gestacional , Hemoglobina Glucada , Valor Predictivo de las Pruebas , Resultado del Embarazo , Humanos , Embarazo , Femenino , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Resultado del Embarazo/epidemiología , Adulto , Glucemia/análisis , Glucemia/metabolismo , Insulina/sangre , Ayuno/sangreRESUMEN
BACKGROUND: Accumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA. OBJECTIVE: This study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM. METHODS: The participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography-Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM. RESULTS: Nine FFAs were respectively associated with an increased risk of GDM (P < 0.05), and four FFAs were respectively associated with a decreased risk of GDM (P < 0.05). SFA risk score was associated with a greater risk of GDM (OR = 1.34, 95% CI: 1.12-1.60), as well as UFA risk score (OR = 1.26, 95% CI: 1.11-1.44), MUFA risk score (OR = 1.70, 95%CI: 1.27-2.26), PUFA risk score (OR = 1.32, 95%CI: 1.09-1.59) and TFA risk score (OR = 2.51, 95%CI: 1.23-5.13). Moreover, joint effects between different types of FFA risk scores on GDM were detected. For instance, compared with those with low risk scores of SFA and UFA, women with high risk scores of SFA and UFA had the highest risk of GDM (OR = 8.53, 95%CI: 2.41-30.24), while the Odds ratio in those with a low risk score of SFA and high risk score of UFA and those with a high risk score of SFA and low risk score of UFA was 6.37 (95%CI:1.33- 30.53) and 4.25 (95%CI: 0.97-18.70), respectively. CONCLUSION: Maternal FFAs during the first trimester were positively associated with the risk of GDM. Additionally, there were joint effects between FFAs on GDM risk. CONDENSATION: Elevated FFA levels in the first trimester increased the risk of GDM.
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Diabetes Gestacional , Ácidos Grasos no Esterificados , Primer Trimestre del Embarazo , Humanos , Femenino , Diabetes Gestacional/epidemiología , Diabetes Gestacional/sangre , Embarazo , Estudios de Casos y Controles , Adulto , Ácidos Grasos no Esterificados/sangre , Primer Trimestre del Embarazo/sangre , Factores de Riesgo , Biomarcadores/sangreRESUMEN
Gestational diabetes mellitus (GDM) is a common disease during pregnancy that has adverse effects on both the mother and fetus. There are currently rare researches on the effect of vitamin supplementation on GDM pregnant mother and their offspring on animal and cell levels systematically. This work supplemented the GDM pregnant mouse model with vitamin D and found that vitamin D can effectively alleviate the hyperglycemia in GDM pregnant mice, increase blood insulin and adiponectin concentrations, and improve GTT and ITT in pregnant mice. In addition, vitamin D can reduce the incidence of death and high birth weight of offspring caused by GDM. The offspring of GDM pregnant mice had higher blood glucose levels in the first 5 weeks after birth compared to the normal group, and then returned to normal levels. Vitamin D can alleviate abnormal glucose metabolism in newborn mice. The therapeutic effect exhibited by vitamin D may be due to their anti-inflammatory effects, as vitamin D supplementation significantly reduces the levels of TFN-?, MCP-1, IL-1? and IL-8 in the blood. Vitamin D also regulates liver lipid metabolism, resulting in a decrease in liver lipid accumulation and a decrease in blood triglycerides (TG) and cholesterol (CHO). The results of this study demonstrate that vitamin D supplementation can serve as an effective treatment strategy for alleviating GDM symptoms. Keywords: Gestational diabetes mellitus, Vitamin D, Glucose metabolism, Anti-inflammatory.
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Glucemia , Diabetes Gestacional , Modelos Animales de Enfermedad , Vitamina D , Animales , Diabetes Gestacional/metabolismo , Diabetes Gestacional/prevención & control , Diabetes Gestacional/sangre , Diabetes Gestacional/tratamiento farmacológico , Femenino , Embarazo , Vitamina D/farmacología , Vitamina D/uso terapéutico , Ratones , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Glucosa/metabolismo , Suplementos Dietéticos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. METHODS: This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11-14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. RESULTS: FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. CONCLUSION: The combination of FPG and IGFBP-2 at early gestation (11-14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.
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Biomarcadores , Diabetes Gestacional , Aprendizaje Automático , Primer Trimestre del Embarazo , Humanos , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Femenino , Embarazo , Estudios de Casos y Controles , Biomarcadores/sangre , Adulto , Primer Trimestre del Embarazo/sangre , China/epidemiología , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Globulina de Unión a Hormona Sexual/análisis , Proteína C-Reactiva/análisis , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Fibronectinas/sangre , Adiponectina/sangre , Glucemia/análisis , Valor Predictivo de las Pruebas , Curva ROC , Modelos LogísticosRESUMEN
BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.
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Gonadotropina Coriónica Humana de Subunidad beta , Diabetes Gestacional , Macrosomía Fetal , Recién Nacido Pequeño para la Edad Gestacional , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo , Humanos , Femenino , Embarazo , Proteína Plasmática A Asociada al Embarazo/análisis , Proteína Plasmática A Asociada al Embarazo/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Primer Trimestre del Embarazo/sangre , Adulto , Estudios de Casos y Controles , Estudios Retrospectivos , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Recién Nacido , Macrosomía Fetal/sangre , Macrosomía Fetal/epidemiología , Finlandia/epidemiología , Factores de Riesgo , Peso al NacerRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM. OBJECTIVES: Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS). METHODS: Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results. RESULTS: The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011-1.104, p = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959-0.999, p = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results. CONCLUSIONS: There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM.
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Diabetes Gestacional , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Deficiencia de Vitamina D , Vitamina D , Diabetes Gestacional/genética , Diabetes Gestacional/sangre , Humanos , Femenino , Embarazo , Vitamina D/sangre , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/sangre , Factores de RiesgoRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. The objectives: The study is designed to measure vaspin in the serum of women with GDM and estimate its association with insulin resistance, HbA1c, HDL, LDL, triglyceride and total cholesterol. METHODS: This study was a case-control study conducted on 90 pregnant women (26 weeks and more), 60 of them patients with GDM, and 30 normal pregnant women as the control group, The blood sample was taken from participating women, and an interview was carried out with them using questionnaire form. vaspin and insulin were measured by ELISA technique, HbA1c was measured by ichroma™, lipid profile, and fasting blood glucose was measured by colourimetric method. RESULT: Vaspin was increased significantly in the patient group in comparison to control (268.98±154.02) ng/ml. Insulin level increased significantly in the patient group (27.88±19.69) ng/ml, HbA1c and blood glucose also increased significantly in the patient group in comparison to the control respectively (5.08±0.613) (126.47±29.05) mg/dl. However, there was no significant difference in insulin resistance, HDL, LDL, TG, and TC. CONCLUSION: The study shows that vaspin was increased in GDM but there is no negative correlation with HbA1c, insulin resistance, and lipid profile.
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Glucemia , Diabetes Gestacional , Hemoglobina Glucada , Resistencia a la Insulina , Insulina , Serpinas , Humanos , Diabetes Gestacional/sangre , Femenino , Embarazo , Serpinas/sangre , Adulto , Irak , Estudios de Casos y Controles , Hemoglobina Glucada/análisis , Glucemia/análisis , Insulina/sangre , Triglicéridos/sangreRESUMEN
This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.
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Diabetes Gestacional , Receptores de Hialuranos , Adulto , Femenino , Humanos , Embarazo , Estudios de Casos y Controles , China/epidemiología , Diabetes Gestacional/genética , Diabetes Gestacional/sangre , Pueblos del Este de Asia/genética , Predisposición Genética a la Enfermedad , Variación Genética , Receptores de Hialuranos/genética , Receptores de Hialuranos/sangre , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: We aimed to determine the best-performing machine learning (ML)-based algorithm for predicting gestational diabetes mellitus (GDM) with sociodemographic and obstetrics features in the pre-conceptional period. METHODS: We collected the data of pregnant women who were admitted to the obstetric clinic in the first trimester. The maternal age, body mass index, gravida, parity, previous birth weight, smoking status, the first-visit venous plasma glucose level, the family history of diabetes mellitus, and the results of an oral glucose tolerance test of the patients were evaluated. The women were categorized into groups based on having and not having a GDM diagnosis and also as being nulliparous or primiparous. 7 common ML algorithms were employed to construct the predictive model. RESULTS: 97 mothers were included in the study. 19 and 26 nulliparous were with and without GDM, respectively. 29 and 23 primiparous were with and without GDM, respectively. It was found that the greatest feature importance variables were the venous plasma glucose level, maternal BMI, and the family history of diabetes mellitus. The eXtreme Gradient Boosting (XGB) Classifier had the best predictive value for the two models with the accuracy of 66.7% and 72.7%, respectively. DISCUSSION: The XGB classifier model constructed with maternal sociodemographic findings and the obstetric history could be used as an early prediction model for GDM especially in low-income countries.
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Índice de Masa Corporal , Diabetes Gestacional , Prueba de Tolerancia a la Glucosa , Aprendizaje Automático , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/sangre , Femenino , Embarazo , Adulto , Glucemia/análisis , Algoritmos , Primer Trimestre del Embarazo , Valor Predictivo de las Pruebas , Paridad , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials. OBJECTIVE: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk. METHODS: Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR-Egger, maximum likelihood, weighted median, and weighted mode. RESULTS: The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), p = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran's Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), p = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), p = 0.408]. CONCLUSIONS: According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required.
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Diabetes Gestacional , Análisis de la Aleatorización Mendeliana , Proteína de Unión a Vitamina D , Vitamina D , Humanos , Femenino , Diabetes Gestacional/sangre , Diabetes Gestacional/genética , Proteína de Unión a Vitamina D/genética , Proteína de Unión a Vitamina D/sangre , Embarazo , Vitamina D/análogos & derivados , Vitamina D/sangre , Factores de Riesgo , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage. METHODS: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities. RESULTS: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia (p > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity (p = 0.001), gestational diabetes (p = 0.03), Premature rupture of membranes (p = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors. CONCLUSIONS: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.
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Potenciales Evocados Auditivos del Tronco Encefálico , Hiperbilirrubinemia Neonatal , Humanos , Femenino , Recién Nacido , Masculino , Estudios Retrospectivos , Hiperbilirrubinemia Neonatal/sangre , Hiperbilirrubinemia Neonatal/fisiopatología , Hiperbilirrubinemia Neonatal/complicaciones , Hiperbilirrubinemia Neonatal/diagnóstico , Factores de Riesgo , Bilirrubina/sangre , Embarazo , Diabetes Gestacional/fisiopatología , Diabetes Gestacional/sangreRESUMEN
AIMS: The present study aimed to investigate the relationship between mean platelet volume (MPV) and the risk of type 2 diabetes mellitus (T2DM), among women with and without a history of gestational diabetes mellitus (GDM). METHODS: Eight thousand one hundred eighty-one parous women of the '2007-2018 National Health and Nutrition Examination Survey (NHANES)' were classified into GDM and non-GDM groups based on self-reported GDM history. We investigated the independent association between the MPV and the risk of T2DM in these groups via multivariable regression analysis. A subgroup analysis was done for the GDM group. RESULTS: After comprehensive adjustment for potential covariates, a significant positive correlation was observed between MPV and the risk of T2DM in women with a history of GDM (OR = 1.50, 95% CI 1.13-2.01, P = 0.006). There was a linear relationship between MPV and T2DM among women with a history of GDM, with each unit increase in MPV increasing the risk of T2DM by 50%. Subgroup analysis and interaction tests revealed a stronger significant effect on women with GDM history who had HbA1c ≥ 7%. CONCLUSIONS: MPV is strongly associated with the incidence of T2DM among U.S. parous women with prior GDM, indicating that MPV may be a potential biomarker of T2DM among women with a history of GDM.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Volúmen Plaquetario Medio , Humanos , Femenino , Diabetes Gestacional/epidemiología , Diabetes Gestacional/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Embarazo , Adulto , Factores de Riesgo , Encuestas Nutricionales , Incidencia , Biomarcadores/sangre , Estudios Transversales , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVE: Our aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship. METHODS: 684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis. RESULTS: In the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95% confidence interval [CI]: 1.475-2.625; P < 0.001). Restricted cubic spline analyses showed a linear relationship between UA and GDM when UA exceeded 222 µmol/L. GDM and UA levels maintained a statistically significant positive correlation in different stratified regression analyses (P < 0.001). However, no evidence of a causal relationship between uric acid and GDM was found by MR analyses with an OR of 1.06 (95% CI: 0.91-1.25) per unit increase in UA. CONCLUSION: There is a positive correlation between UA levels in early pregnancy and the subsequent risk of developing GDM. However, no genetic evidence was found to support a cause-effect relationship between UA and GDM.
Asunto(s)
Diabetes Gestacional , Análisis de la Aleatorización Mendeliana , Ácido Úrico , Humanos , Embarazo , Femenino , Diabetes Gestacional/sangre , Diabetes Gestacional/genética , Diabetes Gestacional/epidemiología , Ácido Úrico/sangre , Estudios de Casos y Controles , Adulto , Factores de RiesgoRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) significantly impacts maternal and infant health both immediately and over the long term, yet effective early diagnostic biomarkers are currently lacking. Thus, it is essential to identify early diagnostic biomarkers for GDM risk screening. Extrachromosomal circular DNA (eccDNA), being more stable than linear DNA and involved in disease pathologies, is a viable biomarker candidate for diverse conditions. In this study, eccDNA biomarkers identified for early diagnosis and assessment of GDM risk were explored. METHODS: Using Circle-seq, we identified plasma eccDNA profiles in five pregnant women who later developed GDM and five matched healthy controls at 11-13 weeks of gestation. These profiles were subsequently analyzed through bioinformatics and validated through outward PCR combined with Sanger sequencing. Furthermore, candidate eccDNA was validated by quantitative PCR (qPCR) in a larger cohort of 70 women who developed GDM and 70 normal glucose-tolerant (NGT) subjects. A ROC curve assessed the eccDNA's diagnostic potential for GDM. RESULTS: 2217 eccDNAs were differentially detected between future GDM patients and controls, with 1289 increased and 928 decreased in abundance. KEGG analysis linked eccDNA genes mainly to GDM-related pathways such as Rap1, MAPK, and PI3K-Akt, and Insulin resistance, among others. Validation confirmed a significant decrease in eccDNA PRDM16circle in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16circle showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001). CONCLUSIONS: Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16circle, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker. TRIAL REGISTRATION: ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.
Asunto(s)
ADN Circular , Diabetes Gestacional , Edad Gestacional , Valor Predictivo de las Pruebas , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/sangre , Diabetes Gestacional/genética , Femenino , Embarazo , Adulto , Estudios de Casos y Controles , Medición de Riesgo , Factores de Riesgo , ADN Circular/sangre , ADN Circular/genética , Primer Trimestre del Embarazo/sangre , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Biomarcadores/sangre , Reproducibilidad de los Resultados , Diagnóstico PrecozRESUMEN
OBJECTIVE: To discuss the correlation between serum progesterone, glycosylated Hemoglobin (HbA1c), and insulin levels in pregnant women with Gestational Diabetes Mellitus (GDM) and the risk of Premature Rupture of Membranes (PROM). METHODS: A retrospective analysis was conducted on 52 patients diagnosed with GDM who also presented with PROM (Observation group) and compared with 89 patients diagnosed with GDM but not complicated with PROM (Control group). Progesterone, insulin, and HbA1c were detected. Risk factors for PROM in GDM patients were analyzed. RESULTS: The observation group had higher HbA1c and fasting blood glucose levels. Poor blood glucose control and GWG are risk factors for PROM in GDM patients. PROM increases adverse pregnancy outcomes in GDM. HbA1c, insulin, and HOMA-IR can predict the risk of PROM in GDM. CONCLUSIONS: The effective prediction of preterm PROM can be achieved through the monitoring of serum HbA1c, insulin levels, and insulin resistance in patients with GDM.
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Glucemia , Diabetes Gestacional , Rotura Prematura de Membranas Fetales , Hemoglobina Glucada , Insulina , Progesterona , Humanos , Femenino , Embarazo , Diabetes Gestacional/sangre , Rotura Prematura de Membranas Fetales/sangre , Estudios Retrospectivos , Hemoglobina Glucada/análisis , Adulto , Progesterona/sangre , Insulina/sangre , Factores de Riesgo , Glucemia/análisis , Resistencia a la Insulina/fisiología , Estudios de Casos y Controles , Adulto JovenRESUMEN
BACKGROUND: Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L). OBJECTIVES: The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes. MATERIALS AND METHODS: A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed. RESULTS: Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women. CONCLUSION: There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women.
Asunto(s)
Hipotiroidismo , Yoduro Peroxidasa , Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hipotiroidismo/inmunología , Adulto , Estudios Prospectivos , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inmunología , Yoduro Peroxidasa/inmunología , Recién Nacido , Autoanticuerpos/sangre , Tirotropina/sangre , Primer Trimestre del Embarazo/sangre , Adulto Joven , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Diabetes Gestacional/sangre , Diabetes Gestacional/inmunología , Enfermedades AsintomáticasRESUMEN
PURPOSE: There is no standardized best method on monitoring of patients with gestational diabetes on diet modification in the country. This study aims to investigate the optimum method of self-monitoring blood glucose. METHODS: This is a randomized clinical trial in a single tertiary centre involving patients with gestational diabetes mellitus (GDM) diagnosed based on NICE guideline on diet modification. The patients are randomized in 1:1 ratio to 4 or 7 points self-monitoring blood glucose. The monitoring was required to be done monthly with ultrasound for fetal growth. Blood was taken at recruitment for measurement of serum HbA1c and fructosamine. RESULTS: A total of 200 patients were recruited. There were significantly more Malay patients in the 7 points group (88.9% vs 78.2%, p = 0.033). Multiparous patients were significantly more in the 4 points group (82.2% vs 68.7%, p = 0.033). Both groups were similar in clinical characteristics. There was no statistical difference in the neonatal outcome particularly fetal macrosomia and admission to neonatal intensive care unit. CONCLUSIONS: In patients with GDM on diet modification, self-blood glucose monitoring using either 4 or 7 points resulted in similar maternal and perinatal outcomes. The research was registered under ClinicalTrials.gov (NCT04101396) on 17/9/2019 ( https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S00098EN&selectaction=Edit&uid=U0004RD4&ts=2&cx=-qlk1w2 ).
Asunto(s)
Automonitorización de la Glucosa Sanguínea , Diabetes Gestacional , Hemoglobina Glucada , Humanos , Femenino , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Embarazo , Malasia , Adulto , Hemoglobina Glucada/análisis , Centros de Atención Terciaria , Glucemia/análisis , Glucemia/metabolismo , Fructosamina/sangre , Recién Nacido , Macrosomía Fetal/prevención & controlRESUMEN
PURPOSE: Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. METHODS: We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. RESULTS: The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). CONCLUSION: MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.