Progression of gestational diabetes mellitus to pregnancy-associated fulminant type 1 diabetes: a case report.

Background: Pregnancy-associated fulminant type 1 diabetes (PF) occurs during pregnancy or within 2 weeks of delivery. Although it occurs infrequently, it is associated with high fetal mortality rate. Few studies have examined whether PF is associated with gestational diabetes mellitus (GDM). Case Description: A 29-year-old woman diagnosed with GDM at 24 weeks of gestation developed a fever, sore throat, nausea and vomiting at 29 weeks of gestation. Ketoacidosis was considered based on her blood ketone and glucose levels and the results of a blood gas analysis. Since the patient's islet function declined rapidly, fluid replacement, insulin therapy, and other treatments were administered. The patient was ultimately diagnosed with PF, and has required ongoing insulin therapy. She delivered a healthy baby girl by elective cesarean section at 37-week gestation. Her blood glucose has been satisfactorily controlled over the 12 months since her acute presentation. Conclusions: PF is characterized by poor maternal and infant outcomes and a high stillbirth rate. Blood glucose should be regularly monitored in pregnant women with GDM. A sudden increase in blood glucose may indicate the possibility of PF, which needs to be managed in a timely manner to avoid adverse pregnancy outcomes.

Healthcare costs attributable to diabetes in pregnancy: A cost of illness study in Tasmania, Australia.

AIMS: To estimate the direct costs during the prenatal, delivery and postpartum periods in mothers with diabetes in pregnancy, compared to those without. METHODS: This study used a population-based dataset from 2004 to 2017, including 57,090 people with diabetes and 114,179 people without diabetes in Tasmania, Australia. Based on diagnostic codes, delivery episodes with gestational diabetes mellitus (GDM) were identified and matched with delivery episodes without diabetes in pregnancy. A group of delivery episodes with pre-existing diabetes was identified for comparison. Hospitalisation, emergency department and pathology costs of these groups were calculated and adjusted to 2020-2021 Australian dollars. RESULTS: There were 2774 delivery episodes with GDM, 2774 delivery episodes without diabetes and 237 delivery episodes with pre-existing diabetes identified. Across the 24-month period, the pre-existing diabetes group required the highest costs, totalling $23,536/person. This was followed by the GDM ($13,210/person), and the no diabetes group ($11,167/person). The incremental costs of GDM over the no diabetes group were $890 (95% CI 635; 1160) in the year preceding delivery; $812 (616; 1031) within the delivery period and $341 (110; 582) in the year following delivery (p < 0.05). Within the year preceding delivery, the incremental costs in the prenatal period were $803 (579; 1058) (p < 0.05). Within the year following delivery, the incremental costs in the postpartum period were $137 (55; 238) (p < 0.05). CONCLUSIONS: Our results emphasised the importance of proper management of diabetes in pregnancy in the prenatal and postpartum periods and highlighted the significance of screening and preventative strategies for diabetes in pregnancy.

Predictive capacity of fetal pancreatic circumference for gestational diabetes mellitus.

OBJECTIVE: To assess the capacity of fetal pancreatic size, before standard blood testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). METHODS: This was a retrospective cohort study of low-risk pregnant women recruited during routine second-trimester fetal anatomical screening at 20-25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent-samples t-test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver-operating-characteristics (ROC) curves. RESULTS: Overall, 195 women were selected for statistical analysis. Twenty-four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD pancreatic circumference centile was significantly higher in the GDM group compared with the non-GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut-off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade-off between sensitivity and specificity achieved at the 75th centile cut-off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut-offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). CONCLUSIONS: Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The mediating effect of e-health literacy on social support and behavioral decision-making on glycemic management in pregnant women with gestational diabetes: a cross-sectional study.

Background: Social support and e-health literacy are closely related to individual health behaviors, while behavior is premised on decision-making. Few studies have identified the relationships among social support, e-health literacy, and behavioral decision-making, and the nature of these relationships among pregnant women with gestational diabetes remains unclear. Therefore, this study aimed to investigate relationships among social support, e-health literacy, and glycemic management behavioral decisions in pregnant women with gestational diabetes. Methods: Using continuous sampling, an online cross-sectional survey was conducted among pregnant women with gestational diabetes who met the inclusion and exclusion criteria at four Class 3 hospitals in Fujian Province from October to December 2023. A structured questionnaire was used to collect data on general characteristics, socioeconomic status, social support, e-health literacy, and behavioral decision-making regarding glycemic management. Descriptive statistical analyses, correlation analyses, and mediation effects were used to assess associations. Results: A total of 219 pregnant women with gestational diabetes participated, and 217 valid results were obtained. The level of glycemic management behavior decision-making in women with gestational diabetes was positively correlated with e-health literacy (r = 0.741, p < 0.01) and with perceived social support (r = 0.755, p < 0.01). E-health literacy was positively correlated with perceived social support (r = 0.694, p < 0.01). The indirect effect of perceived social support on glycemic management behavior decisions through e-health literacy (a*b) was 0.153, accounting for 38% of the total effect. Conclusion: Social support and e-health literacy in pregnant women with gestational diabetes are related to behavioral decision-making in glycemic management. The results of this study provide a reference for developing targeted measures to improve glycemic management behaviors in pregnant women with gestational diabetes, which is crucial for achieving sustainable glycemic management.

TGFß1, SNAIL2, and PAPP-A Expression in Placenta of Gestational Diabetes Mellitus Patients.

Background: Gestational diabetes mellitus (GDM) is a pregnancy-related diabetic condition that may cause serious complications. However, its pathogenesis remains unclear. Placental damage due to GDM may lead to several health issues that cannot be ignored. Thus, we aimed to identify the mechanisms underlying GDM by screening differentially expressed genes (DEGs) related to vascular endothelial cells in the GDM databases and verify the expression of these DEGs in the placentas of women afflicted by GDM. Methods: We used GDM microarray datasets integrated from the Gene Expression Omnibus (GEO) database. Functional annotation and protein-protein interaction (PPI) analyses were used to screen DEGs. Placental tissues from 20 pregnant women with GDM and 20 healthy pregnant women were collected, and differential gene expression in the placental tissues was verified via qRT-PCR, western blotting, and immunofluorescence. Results: Bioinformatics analysis revealed three significant DEGs: SNAIL2, PAPP-A, and TGFß1. These genes were all predicted to be underexpressed in patients with GDM. The results of qRT-PCR, western blot, and immunofluorescence analyses indicated that SNAIL2 and PAPP-A in the placenta tissue of patients with GDM were significantly underexpressed. However, TGFß1 in the placenta tissues of GDM was significantly overexpressed. Conclusion: SNAIL2, TGFß1, and PAPP-A may affect the placentas of pregnant women with GDM, warranting further investigation.

Association of Gestational Diabetes With Subclinical Cardiovascular Disease.

Background: Gestational diabetes mellitus (GDM) is associated with increased long-term risk of cardiovascular disease but the cardiovascular structural and functional changes that contribute to risk are not well understood. Objectives: The purpose of this study was to determine whether GDM is associated with adverse cardiac remodeling and endothelial dysfunction a decade after delivery, independent of type 2 diabetes. Methods: Women with deliveries between 2008 and 2009 were initially selected from a prospective clinical cohort. Pregnancy history was chart abstracted and a follow-up study visit was conducted at 8 to 10 years postpartum. Cardiac structure and function were assessed with echocardiography. Endothelial function was measured with peripheral arterial tonometry and glycocalyx analysis. Results: Among 254 women assessed at an average age of 38 years, 53 (21%) had prior GDM. At follow-up, women with GDM had more incident prediabetes or diabetes (58% vs 20% without GDM), more impairment in peripheral arterial tonometry (reactive hyperemia 1.58 vs 1.95; P = 0.01) and reduced perfusion, a marker of glycocalyx assessment (red blood cell filling 0.70 ± 0.04 vs 0.72 ± 0.05; P < 0.01). Despite adjustment for demographic and reproductive characteristics, women with GDM had great septal wall thickness by 8% (95% CI: 2.3%-14.7%) and worse diastology with higher E/E' by 11% (95% CI: 1.1%-21.5%). After additional adjustment for diabetes and prediabetes, several parameters remained significantly impaired. Conclusions: Having GDM within the past decade was associated with more adverse cardiac structure/function and vascular endothelial function. Some, but not all, risks may be mediated through the development of prediabetes or type 2 diabetes. Enhanced preventive efforts are needed to mitigate cardiovascular risk among women with GDM.

Women with Gestational Diabetes Mellitus Have Greater Formula Supplementation in the Hospital and at Home Despite Intention to Exclusively Breastfeed.

Background: Women with gestational diabetes mellitus (GDM) have lower rates of exclusive breastfeeding compared with women without diabetes. Objectives: To assess associations between GDM and breastfeeding intentions and attitudes, formula supplementation, reasons for formula supplementation, and knowledge of type 2 diabetes mellitus (T2DM) risk reduction associated with breastfeeding among U.S. mothers. Design/Methods: Participants completed an online survey assessing infant feeding knowledge, attitudes, and practices; demographics; and pregnancy-related medical history. Multivariable logistic regression was used to estimate adjusted odds ratios for formula supplementation in the hospital and at home. Results: Of 871 respondents, a smaller proportion of women with GDM compared with women without diabetes intended to exclusively breastfeed. There were no differences between groups in attitudes toward public breastfeeding, attitudes toward breastfeeding beyond infancy, or actual duration of any breastfeeding. Approximately one in four participants believed that breastfeeding mothers may be less likely to develop T2DM, regardless of GDM status. Among those who intended to exclusively breastfeed, GDM was associated with higher odds of formula supplementation in the hospital (adjusted odds ratio [OR] 1.75, 95% confidence interval [CI] 0.97-3.18) and at home (adjusted OR 2.02, 95% CI 1.05-3.89). "Medical reasons," which was reported as an important reason for formula supplementation, was reported more frequently by women with GDM. Conclusions: Women with GDM who intended to exclusively breastfeed had higher odds of in-hospital and at-home formula supplementation, cited medical reasons as a main reason for formula supplementation more often, and were largely unaware of T2DM risk reduction associated with breastfeeding.

Decreased complexity of glucose time series index associated with adverse pregnancy outcomes in gestational diabetes mellitus.

AIM: We investigated the relationship between the complexity of the glucose time series index (CGI) during pregnancy and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In this retrospective cohort study, 388 singleton pregnant women with GDM underwent continuous glucose monitoring (CGM) at a median of 26.86 gestational weeks. CGI was calculated using refined composite multiscale entropy based on CGM data. The participants were categorized into tertiles according to their baseline CGI (CGI <2.32, 2.32-3.10, ≥3.10). Logistic regression was used to assess the association between CGI and composite adverse outcomes or large for gestational age (LGA). The discrimination performance of CGI was estimated using receiver operating characteristic analysis. RESULTS: Of the 388 participants, 71 (18.3%) had LGA infants and 63 (16.2%) had composite adverse outcomes. After adjustments were made for confounders, compared with those with a high CGI (CGI ≥3.10), participants with a low CGI (CGI <2.32) had a higher risk of composite adverse outcomes (odds ratio: 12.10, 95% confidence interval: 4.41-33.18) and LGA (odds ratio: 12.68, 95% confidence interval: 4.04-39.75). According to the receiver operating characteristic analysis, CGI was significantly better than glycated haemoglobin and conventional CGM indicators for the prediction of adverse pregnancy outcomes (all p < .05). CONCLUSION: A lower CGI during pregnancy was associated with composite adverse outcomes and LGA. CGI, a novel glucose homeostasis predictor, seems to be superior to conventional glucose indicators for the prediction of adverse pregnancy outcomes in women with GDM.

"The Best I Could": Future Orientations for Danish Women with Gestational Diabetes.

The introduction of personalized medicine marks a shift in pregnancy-related screening, from fetal to maternal health risks putting the pregnant woman's future orientations center stage. Drawing on fieldwork from pregnancy outpatient clinics and 11 interviews with pregnant women diagnosed with gestational diabetes and offered genetic testing, we use their experiences of time to explore how futurity is reshaped by notions of early detection and at-riskness. We offer the concept of "future prism" to capture how multiple situations of orienting toward the future shape and circumscribe one's experience of the future - an orientation that makes genetic testing almost impossible to refuse.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus.

BACKGROUND: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? METHODS: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. RESULTS: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15-38)  vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. CONCLUSIONS: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

Management of gestational diabetes mellitus via nutritional interventions: The relevance of gastric emptying.

Gestational diabetes mellitus (GDM) represents one of the most common medical complications of pregnancy and is important to the well-being of both mothers and offspring in the short and long term. Lifestyle intervention remains the mainstay for the management of GDM. The efficacy of nutritional approaches (e.g. calorie restriction and small frequent meals) to improving the maternal-neonatal outcomes of GDM was attested to by Chinese population data, discussed in two articles in recent issues of this journal. However, a specific focus on the relevance of postprandial glycaemic control was lacking. Postprandial rather than fasting hyperglycaemia often represents the predominant manifestation of disordered glucose homeostasis in Chinese women with GDM. There is now increasing appreciation that the rate of gastric emptying, which controls the delivery of nutrients for digestion and absorption in the small intestine, is a key determinant of postprandial glycaemia in both health, type 1 and 2 diabetes. It remains to be established whether gastric emptying is abnormally rapid in GDM, particularly among Chinese women, thus contributing to a predisposition to postprandial hyperglycaemia, and if so, how this influences the therapeutic response to nutritional interventions. It is essential that we understand the role of gastric emptying in the regulation of postprandial glycaemia during pregnancy and the potential for its modulation by nutritional strategies in order to improve post-prandial glycaemic control in GDM.

Gestational diabetes mellitus and the hearing of newborns:A nested case-control study in tropical province of China.

OBJECTIVE: This study aims to determine the association of gestational diabetes mellitus (GDM) and the results of newborn hearing screening(NHS). METHODS: A nested case-control study was conducted in a cohort of newborns who were born between June 2021 to December 2021 and underwent neonatal hearing screening.GDM was diagnosed according to the 75 g 2 h oral glucose tolerance test (OGTT) at 24-28 gestational weeks.A total of 369 pregnant women at the same hospital were individually matched in a 1:2 ratio by maternal age (±2 years), gestational age (±3 days) and sex of newborn.Chi-square test was utilized to evaluate associations between GDM and the results of NHS. RESULTS: Abnormal NHS results in the GDM group was more frequent than non-GDM group.When comparing the two groups (GDM case and contol), we found significant differences (p < 0.05) between them.Whereas the difference was not statistically significant (p > 0.05) by delivery modes in both case and control groups. CONCLUSION: Maternal history of GDM could lead to significantly higher failling rate of NHS.

Prospective evaluation of ultrasonographic fetal cardiac morphometry and functions in the third trimester of pregnancies with gestational diabetes mellitus.

OBJECTIVE: This study aimed to compare cardiac morphological and functional changes in fetuses of patients with diet-regulated gestational diabetes mellitus (GDM-A1), insulin-regulated GDM (GDM-A2), and a control group. METHOD: A prospective cohort study included pregnant women aged 18-40 years with singleton pregnancies. Fetal biometric, cardiac morphological, and functional measurements were recorded using Z-scores at 34-37 weeks of gestation. RESULTS: The study included 87 patients. Both right and left ventricular wall thicknesses were significantly different between the three groups (p < 0.001 and p < 0.001, respectively). Z-scores of the mitral valve, left and right EDD were significantly lower in GDM-A1 and GDM-A2 groups compared to the control group (p < 0.001, p < 0.001, p = 0.002, respectively). Right and left ventricular areas were decreased only in GDM-A2 group compared to the control group (p = 0.003 and p = 0.001, respectively). MPI and IVRT values were also significantly higher in the same groups (p = 0.016, p < 0.001, respectively). CONCLUSION: Gestational diabetes increased IVS and ventricular wall thicknesses in both right and left ventricles, irrespective of whether it was controlled by diet or insulin. Cardiac functional changes were observed in the GDM-A2 group.

Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.

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.

Risk factors and diagnostic performance of predictors as a screening technique for gestational diabetes mellitus: a retrospective cross-sectional study.

Background: Gestational diabetes mellitus (GDM) is a condition that can have negative impacts on both mother and baby. Detecting GDM early is crucial, and fasting plasma glucose (FPG) has been suggested as a possible screening method. This retrospective cross-sectional study aims to investigate potential risk factors and complications associated with GDM. Additionally, it aims to establish the diagnostic performance of predictive factors as a screening method for GDM. Methods: Data were collected from the medical records of 247 pregnant women who visited outpatient Obstetrics clinics between 2021 and 2022. The study investigated potential risk factors and complications associated with GDM, including impaired fasting glucose/impaired glucose tolerance (IFG/IGT), family history of diabetes mellitus (DM), and medical conditions. Moreover, the study evaluated the diagnostic performance of potential predictors as screening techniques for GDM. Results: The study found that IFG/IGT (P<0.001), a history of GDM (P<0.001), and a family history of DM (P=0.022) were significant factors associated with GDM. Healthy individuals had a lower risk of developing GDM (P<0.001). No significant correlation was found between GDM and macrosomia, hypertension, polycystic ovarian syndrome, or other obstetric complications. Although a weak association was observed between fasting blood glucose levels during the first trimester and GDM, it was not significant. Conclusion: In conclusion, this study found that IFG/IGT and a past history of GDM were significantly associated with GDM. Additionally, a family history of diabetes increased the likelihood of developing GDM, while no significant association was found between GDM and other obstetric complications. Although a weak association was observed between fasting blood glucose levels during the first trimester and GDM, it was not statistically significant.

Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism.

The incidence rate of gestational diabetes mellitus (GDM) remains high among pregnant women in the second trimester of pregnancy. However, the main clinical approach to alleviate the symptoms of GDM is to control the diet. Our study explored the therapeutic effects of omega-3 fatty acids (ω-3 FAs) on GDM at the cellular and animal levels. We found that ω-3 FAs can promote the transformation of M0 macrophages into anti-inflammatory M2 macrophages. The transformed M2 macrophages promoted ß-oxidation and reduced hepatocyte lipid synthesis (P < 0.05), thereby promoting hepatic function and preventing the excessive accumulation of lipid droplets in the hepatocyte cell line HepG2. Supplementation of ω-3 FAs in pregnant GDM mice significantly reduced fasting blood glucose levels, glucose tolerance test, and insulin tolerance test indices, and lipid accumulation in the liver and effectively prevented the occurrence of liver fibrosis (P < 0.05). These therapeutic effects may be mediated through the anti-inflammatory effects of ω-3 FAs (P < 0.05). ω-3 FAs also had positive effects on the offspring of pregnant GDM mice, as demonstrated by reduced birth mortality and improved glycemic stabilization (P < 0.05). In conclusion, this study provides a possible translational medicine strategy for the treatment of GDM.

Circulating extracellular vesicle-derived miR-1299 disrupts hepatic glucose homeostasis by targeting the STAT3/FAM3A axis in gestational diabetes mellitus.

BACKGROUND: Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. RESULTS: Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3'-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain-of-function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. CONCLUSIONS: These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.

Association between mean platelet volume and the risk of type 2 diabetes mellitus among women with history of gestational diabetes mellitus.

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.

Uric acid and risk of gestational diabetes mellitus: an observational study and mendelian randomization analysis.

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.