Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

Improved neonatal outcomes in pregnancies with coexisting gestational diabetes and preeclampsia in normal birthweight neonates- insights from a retrospective cohort study.

INTRODUCTION: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET). METHODS: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance. RESULTS: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions. DISCUSSION: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM. CLINICAL TRIAL REGISTRATION: approval of local ethics committee WOMC-19-0152.

Improving maternal and neonatal outcomes for women with gestational diabetes through continuity of midwifery care: A cross-sectional study.

PROBLEM: Gestational Diabetes Mellitus (GDM) is a complication of pregnancy which may exclude women from midwife-led models of care. BACKGROUND: There is a paucity of research evaluating the safety and feasibility of continuity of midwifery care (CoMC) for women with GDM. AIM: To investigate the impact of CoMC on maternal and neonatal outcomes, for otherwise low-risk women with GDM. METHODS: This exploratory cross-sectional study observed maternal and neonatal outcomes including onset of labour, augmentation, labour analgesia, mode of birth, perineal trauma, gestation at birth, shoulder dystocia, infant birth weight, neonatal feeding at discharge. FINDINGS: Participants were 287 otherwise low-risk pregnant women, who developed GDM, and either received CoMC (n=36) or standard hospital maternity care (non-CoMC) (n=251). Women with GDM who received CoMC were significantly more likely to experience an spontaneous onset of labour (OR 6.3; 95% CI 2.7-14.5; p<.001), labour without an epidural (OR 4.2; 95% CI 2.0 - 9.2,<0.001) and exclusively breastfeed (OR 4.3; 95% CI 1.26 - 14.32; p=0.02). DISCUSSION: Receiving CoMC may be a public health initiative which not only improves maternal and neonatal outcomes, but also long-term morbidity associated with GDM. CONCLUSION: Findings provide preliminary evidence suggesting CoMC improves maternal and neonatal outcomes and is likely a safe and viable option for otherwise low-risk women with GDM. Larger studies are recommended to confirm findings and explore the full impact of CoMC for women with GDM.

A retrospective cohort study on the influencing factors for macrosomia in singleton pregnancies.

To explore the influencing factors of singletons with macrosomia, and to develop interventions for the prevention of macrosomia. A retrospective cohort study was conducted on 26,379 pregnant women who established the Maternal and Child Health Record and gave birth from January 1, 2019 to December 31, 2019 in a community health service center in Haidian district, Beijing. The study analyzed factors such as maternal age, ethnicity, education level, prepregnancy body mass index (BMI), parity, folic acid supplementation, gestational diabetes mellitus, gestational hyper, hypothyroidism in pregnancy (including subhypothyroidism), hyperthyroidism in pregnancy, and infant gender. Univariate analysis was performed using the χ2 test, and multivariate analysis was performed using non-conditional multivariate logistic regression analysis. Out of 26,379 live births, 5.8% (1522/26,379) were macrosomia and 94.2% (24,857/26,379) were non-macrosomia. Univariate analysis revealed that maternal age, prepregnancy BMI, education level, parity, hypothyroidism during pregnancy, and infant gender were identified as influencing factors for macrosomia (P < .05). Multivariate analysis showed that maternal age ≥ 35 years, education level of high school or below, pre-pregnancy BMI, hypothyroidism, male infant, and parity were all influencing factors for macrosomia (P < .05). Prepregnancy overweight or obesity, male infants, multiparity, and low education level are risk factors for macrosomia. Multiple factors can contribute to macrosomia, and therefore, maternal health care should be strengthened, and early interventions should be taken for the above-mentioned factors in the local area.

Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study.

INTRODUCTION: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown. METHODS AND ANALYSIS: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT05124808.

Fatty acids and their metabolites (resolvins) are altered in women with gestational diabetes mellitus (GDM).

The maternal fatty acid status plays a key role in influencing pregnancy outcomes. Omega-3 fatty acids are the precursors for E-series (RvE) and D-series resolvins (RvD) and possess anti-inflammatory properties. Pregnancy complications like gestational diabetes mellitus (GDM) are associated with excess maternal inflammation. This study reports the levels of maternal fatty acids across gestation in GDM and non-GDM women, placental fatty acids, resolvins and their association with the maternal fatty acid status. Pregnant women were recruited at 11-14 (V1) weeks and followed at 18-22 (V2) and 26-28 (V3) weeks and at delivery (V4). A total of 209 women who were diagnosed as GDM and 207 non-GDM women were included in this study. Fatty acids were estimated using gas chromatography. The protein levels of resolvins (RvE1, RvE2, RvD1 and RvD2) were measured using ELISA kits. Total PUFAs, eicosapentaenoic acid (EPA), omega-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were lower, while saturated fatty acid (SFA) and alpha-linolenic acid (ALA) levels were higher in GDM women at 18-22 weeks. Placental AA was lower (p < 0.05) in women with GDM. Placental protein levels of RvE1, RvD1 and RvD2 were lower (p < 0.001 for all) in the GDM group. The maternal delta 5 desaturase index was positively associated, while erythrocyte omega-3 and omega-6 fatty acids were negatively associated with RvE2 at 11-14 weeks. Placental LA and ALA were positively associated with RvD1 and RvD2 (p < 0.05, for both), respectively. Our findings suggest that the maternal fatty acid status influences pro-resolving mediators which may lead to increased inflammation in GDM.

Diabetes in pregnancy: Women's views of care in a multi-ethnic, low socioeconomic population with midwifery continuity-of-care.

BACKGROUND: Diabetes in pregnancy is diagnosed in 6% of pregnancies annually in Aotearoa-New Zealand, disproportionately affecting multi-ethnic, low socio-economic women. Little is known about the care experience of this population within the model of midwifery continuity-of-care, including views of telehealth care. AIM: Increase understanding of the experience of diabetes in pregnancy care, including telehealth, among multi-ethnic, low socio-economic women receiving midwifery continuity-of-care. METHODS: Qualitative interview study with primarily indigenous and migrant women who had diabetes in pregnancy and gave birth 6-18 months previously. Interviewers were matched with participants by ethnicity. Transcripts were analysed using Framework analysis. RESULTS: Participants were 19 women (5 Maori, 5 Pacific Peoples, 5 Asian, 4 European). Data analysis revealed three key themes: 1) 'shock, shame, and adjustment' to the diagnosis 2) 'learning to manage diabetes in pregnancy' and 3) 'preparation for birth and beyond' to the postpartum period. DISCUSSION: Receiving the diagnosis of diabetes in pregnancy was a shock. Managing diabetes during pregnancy was particularly challenging for indigenous and migrant women, who wished for better access to culturally appropriate dietary and lifestyle information. Women appreciated having options of telehealth and face-to-face consultations. Preparation for birth and postpartum diabetes follow-up were areas requiring significant improvement. Challenges were mitigated through care from a consistent diabetes specialist midwife and community-based midwifery continuity-of-care. CONCLUSION: Midwives were the backbone of diabetes in pregnancy care for this multi-ethnic, low socio-economic population. Care could be improved with more culturally appropriate diet and lifestyle information, better birth preparation, and expanded postpartum diabetes support.

The association between prepregnancy dietary fatty acids and risk of gestational diabetes mellitus: A prospective cohort study.

BACKGROUND & AIMS: Epidemiologic studies have examined the association between dietary fatty acids and type 2 diabetes risk in general populations. Evidence regarding their associations with gestational diabetes mellitus (GDM) risk remains limited. This study aimed to evaluate prepregnancy fatty acids intake in relation to GDM risk. METHODS: 3,725 pregnant women from the Xi'an Birth Cohort Study who were free of previous GDM or pre-existing chronic diseases were included. Dietary intake of total fat and individual fatty acids (including saturated fatty acids [SFA], monounsaturated fatty acids [MUFA], polyunsaturated fatty acids [PUFA], and trans fatty acids) during the year preceding pregnancy was assessed by a validated food-frequency questionnaire before 16 weeks of gestation. GDM was confirmed based on the 75-g oral glucose tolerance test. Log-binomial or modified Poisson regression models were applied to estimate the relative risks (RRs) and 95 % confidence intervals (95%CIs) of GDM for fatty acids intake. Generalized linear regression was adopted for blood glucose levels with fatty acids intake. RESULTS: 644 (17.3 %) incident GDM cases were confirmed in our study. Participants in the highest intake of total fat substituting for carbohydrates had a 33 % reduced risk of GDM than those in the lowest intake (RR:0.67; 95%CI:0.55,0.81). For individual fatty acids, only PUFA intake was associated with a lower risk of GDM, with RR comparing extreme tertiles of 0.61 (95%CI:0.49,0.76). Each 2 % increase in energy from total fat and PUFA replacing carbohydrates decreased the risk of GDM by 6 % (95%CI:3 %,9 %) and 15 % (95%CI:9 %,21 %), respectively. Similar inverse associations with intake of total fat and PUFA were observed for blood glucose levels. Further analyses of SFA substitution showed that replacement of 2 % energy from SFA with PUFA and MUFA was associated with 26 % (RR:0.74; 95%CI:0.62,0.88) and 30 % (RR:0.70; 95%CI:0.50, 0.98) decreased risk of GDM, respectively. CONCLUSIONS: Greater intake of total fat and PUFA before pregnancy was associated with lower risk of GDM when replacing carbohydrates. Substitution SFA with PUFA and MUFA was also inversely associated with GDM risk. These findings support the important role of optimal dietary fatty acids composition in the prevention of GDM.

Integrated health system intervention aimed at reducing type 2 diabetes risk in women after gestational diabetes in South Africa (IINDIAGO): a randomised controlled trial protocol.

INTRODUCTION: South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months' post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package. METHODS AND ANALYSES: Convergent parallel mixed-methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24-36 weeks' gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6-8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6-8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention. ETHICS AND DISSEMINATION: Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peer-reviewed journals and presentations to key South African Government stakeholders and health service providers. PROTOCOL VERSION: 1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries. TRIAL REGISTRATION NUMBER: PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).

Ferritin and iron supplements in gestational diabetes mellitus: less or more?

Iron metabolism has been found to be closely related to gestational diabetes mellitus (GDM). Excessive ferritin levels were shown to be related to an increased risk of GDM because of iron overload which may lead to insulin resistance and ß-cell injury by enhancing oxidative stress and inflammatory responses. On the contrary, insufficient ferritin levels can cause a number of obstetric complications, such as high incidence rates of anaemia and gestational hypertension. Therefore, high or low ferritin levels may have adverse effects on the mother and the foetus, putting clinicians in a dilemma when giving pregnant women iron supplements. This also explains why there have been more conflicting findings in the studies on dietary or oral iron supplementation during pregnancy. Hence, there is an urgent need for more evidence and strategies for appropriate recommendations for ferritin levels and iron supplementation during pregnancy to prevent iron insufficiency without causing iron overload and increasing the risk of GDM. Therefore, we gave an updated review on the association of GDM with ferritin metabolism, ferritin levels and iron supplementation based on the summary of the latest research.

Inositol supplementation for the prevention and treatment of gestational diabetes mellitus: a meta-analysis of randomized controlled trials.

BACKGROUND: Inositol is a potential new therapeutic agent for gestational diabetes mellitus (GDM), but its effectiveness is still controversial. The aim of the report was to evaluate the effectiveness of inositol to preventing or reducing the severity of GDM. METHODS: We searched PubMed, EmBase, Web of science, Cochrane library databases, Clinicaltrials.gov, and International Clinical Trials Registry Platform for randomized controlled trials (RCTs) assessing the effectiveness of inositol supplementation to prevent and treat GDM. This meta-analysis was performed using the random-effects model. RESULTS: A total of 7 RCTs (1319 pregnant women at high risk of GDM) were included in the meta-analysis. The meta-analysis found that inositol supplementation resulted in a significantly lower incidence of GDM in the inositol versus the control group (odds ratio [OR] 0.40; 95% confidence interval [CI] 0.24-0.67; P = 0.0005). The inositol group had improved fasting glucose oral glucose tolerance test (FG OGTT; mean difference [MD] = - 3.20; 95% CI - 4.45 to - 1.95; P < 0.00001), 1-h OGTT (MD = - 7.24; 95% CI - 12.23 to - 2.25; P = 0.004), and 2-h OGTT (MD = - 7.15; 95% CI - 12.86 to - 1.44; P = 0.01) results. Inositol also reduced the risk of pregnancy-induced hypertension (OR 0.37; 95% CI 0.18-0.75; P = 0.006) and preterm birth (OR 0.35; 95% CI 0.18-0.69; P = 0.003). A meta-analysis of 4 RCTs including 320 GDM patients showed that the patients' insulin resistance (P < 0.05) and neonatal hypoglycemia risk (OR 0.10, 95% CI 0.01-0.88; P = 0.04) were lower in the inositol than in the control group. CONCLUSIONS: Inositol supplementation during pregnancy has the potential to prevent GDM, improve glycemic control, and reduce preterm birth rates.

MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies.

BACKGROUND: Hyperglycemia from pregestational diabetes mellitus induces neural tube defects in the developing fetus. Folate supplementation is the only effective way to prevent neural tube defects; however, some cases of neural tube defects are resistant to folate. Excess folate has been linked to higher maternal cancer risk and infant allergy. Therefore, additional interventions are needed. Understanding the mechanisms underlying maternal diabetes mellitus-induced neural tube defects can identify potential targets for preventing such defects. Despite not yet being in clinical use, growing evidence suggests that microRNAs are important intermediates in embryonic development and can serve as both biomarkers and drug targets for disease intervention. Our previous studies showed that maternal diabetes mellitus in vivo activates the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in the developing embryo and that a high glucose condition in vitro reduces microRNA-322 (miR-322) levels. IRE1α is an RNA endonuclease; however, it is unknown whether IRE1α targets and degrades miR-322 specifically or whether miR-322 degradation leads to neural tube defects via apoptosis. We hypothesize that IRE1α can inhibit miR-322 in maternal diabetes mellitus-induced neural tube defects and that restoring miR-322 expression in developing neuroepithelium ameliorates neural tube defects. OBJECTIVE: This study aimed to identify potential targets for preventing maternal diabetes mellitus-induced neural tube defects and to investigate the roles and relationship of a microRNA and an RNA endonuclease in mouse embryos exposed to maternal diabetes mellitus. STUDY DESIGN: To determine whether miR-322 reduction is necessary for neural tube defect formation in pregnancies complicated by diabetes mellitus, male mice carrying a transgene expressing miR-322 were mated with nondiabetic or diabetic wide-type female mice to generate embryos with or without miR-322 overexpression. At embryonic day 8.5 when the neural tube is not yet closed, embryos were harvested for the assessment of 3 miR-322 transcripts (primary, precursor, and mature miR-322), tumor necrosis factor receptor-associated factor 3 (TRAF3), and neuroepithelium cell survival. Neural tube defect incidences were determined in embryonic day 10.5 embryos when the neural tube should be closed if there is no neural tube defect formation. To identify which miR-322 transcript is affected by maternal diabetes mellitus and high glucose conditions, 3 miR-322 transcripts were assessed in embryos from dams with or without diabetes mellitus and in C17.2 mouse neural stem cells treated with different concentrations of glucose and at different time points. To determine whether the endonuclease IRE1α targets miR-322, small interfering RNA knockdown of IRE1α or overexpression of inositol-requiring transmembrane kinase/endoribonuclease 1α by DNA plasmid transfection was used to determine the effect of IRE1α deficiency or overexpression on miR-322 expression. RNA immunoprecipitation was performed to reveal the direct targets of inositol-requiring transmembrane kinase/endoribonuclease 1α. RESULTS: Maternal diabetes mellitus suppressed miR-322 expression in the developing neuroepithelium. Restoring miR-322 expression in the neuroepithelium blocked maternal diabetes mellitus-induced caspase-3 and caspase-8 cleavage and cell apoptosis, leading to a neural tube defect reduction. Reversal of maternal diabetes mellitus-inhibited miR-322 via transgenic overexpression prevented TRAF3 up-regulation in embryos exposed to maternal diabetes mellitus. Activated IRE1α acted as an endonuclease and degraded precursor miR-322, resulting in mature miR-322 reduction. CONCLUSION: This study supports the crucial role of the IRE1α-microRNA-TRAF3 circuit in the induction of neuroepithelial cell apoptosis and neural tube defect formation in pregnancies complicated by diabetes mellitus and identifies IRE1α and miR-322 as potential targets for preventing maternal diabetes mellitus-induced neural tube defects.

The impact of fish oil and/or probiotics on serum fatty acids and the interaction with low-grade inflammation in pregnant women with overweight and obesity: secondary analysis of a randomised controlled trial.

N-3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU, each daily). Blood samples were collected in early (n 431) and late pregnancy (n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n-3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n-3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n-3 LC-PUFA were linked with an increased risk for GDM.

The holistic maternity care needs of women with Gestational Diabetes Mellitus: A systematic review with thematic synthesis.

PROBLEM: Models of care for women with gestational diabetes mellitus (GDM) have evolved in an ad hoc way and do not meet women's needs. BACKGROUND: GDM affects 50,000 Australian women per annum with prevalence quadrupling in the last ten years. Many health services are struggling to provide a quality service. People with diabetes are calling for care that focuses on their wellbeing more broadly. AIM: To examine the holistic (emotional, social, economic, and spiritual) care needs of women with GDM. METHODS: Qualitative and mixed-methods studies capturing the healthcare experiences of women with GDM were searched for in CINAHL, Medline, Web of Science and Scopus. English-language studies published between 2011 and 2023 were included. Quality of studies was assessed using Crowe Critical Appraisal Tool and NVIVO was used to identify key themes and synthesise data. FINDINGS: Twenty-eight studies were included, representing the experiences of 958 women. Five themes reflect women's holistic needs through their journey from initial diagnosis to postpartum: psychological impact, information and education, making change for better health, support, and care transition. DISCUSSION: The biomedical, fetal-centric model of care neglects the woman's holistic wellbeing resulting in high levels of unmet need. Discontinuity between tertiary and primary services results in a missed opportunity to assist women to make longer term changes that would benefit themselves (and their families) into the future. CONCLUSIONS: The provision of holistic models of care for this cohort is pivotal to improving clinical outcomes and the experiences of women with GDM.

N1-methylnicotinamide impairs gestational glucose tolerance in mice.

N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays antidiabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in a gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with a high-fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to establish the GDM model. Pregnant mice were treated with 0.3% or 1% MNAM during gestation. MNAM supplementation in CHOW diet and HFD both impaired glucose tolerance at gestational day 14.5 without changes in insulin tolerance. However, MNAM supplementation reduced hepatic lipid accumulation as well as mass and inflammation in visceral adipose tissue. MNAM treatment decreased GLUT4 mRNA and protein expression in skeletal muscle, where NAD+ salvage synthesis and antioxidant defenses were dampened. The NAD+/sirtuin system was enhanced in liver, which subsequently boosted hepatic gluconeogenesis. GLUT1 protein was diminished in placenta by MNAM. In addition, weight of placenta, fetus weight, and litter size were not affected by MNAM treatment. The decreased GLUT4 in skeletal muscle, boosted hepatic gluconeogenesis and dampened GLUT1 in placenta jointly contribute to the impairment of glucose tolerance tests by MNAM. Our data provide evidence for the careful usage of MNAM in treatment of GDM.

Comparative Study of the Impact of Metformin Versus Insulin on Adverse Pregnancy Outcomes in Women Diagnosed with Gestational Diabetes Mellitus: A Meta-Analysis.

Objective: This systematic comparative analysis aimed to assess the efficacy of metformin (MET) versus insulin (INS) in the treatment of gestational diabetes mellitus (GDM), providing valuable insights for future GDM management strategies. Methods: We conducted a comprehensive search of clinical studies related to MET and INS interventions in GDM through online literature databases, applying predefined inclusion and exclusion criteria. The quality of the included studies was rigorously evaluated. Data on fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), pregnancy weight gain (PWG), premature delivery rate (PDR), and neonatal outcomes among GDM patients were extracted and analyzed using Review Manager 5.3 software. Results: We identified eleven high-quality studies comprising 8679 participants following careful screening and assessment. Our meta-analysis revealed a significant reduction in the incidence of excessive PWG and neonatal hypoglycemia in the MET treatment group (research group) compared to the INS treatment group (control group) (P < .05). Conclusions: Our findings support the effectiveness and safety of MET in achieving optimal blood glucose control in GDM. These results suggest the potential for broader clinical adoption of MET in GDM management.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

The efficacy of magnesium supplementation for gestational diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of magnesium supplementation is unclear for the treatment of gestational diabetes. This meta-analysis aimed to study the efficacy of magnesium supplementation for glycemic control and pregnant outcomes in women with gestational diabetes. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been systematically searched up to July 2023, and we included randomized controlled trials (RCTs) assessing the efficacy of magnesium supplementation for gestational diabetes. The meta-analysis was performed using the random-effect model or fixed-effect model based on the heterogeneity. RESULTS: Five RCTs and 266 patients were included in the meta-analysis. Overall, compared with control intervention for gestational diabetes, magnesium supplementation was able to significantly decrease FPG (MD = -7.33 mg/dL; 95 % CI = -7.64 to -7.02 mg/dL; P < 0.00001) and HOMA-IR (MD = -0.99; 95 % CI = -1.76 to -0.22; P = 0.01), but resulted in no obvious impact on serum insulin (MD = -4.17 µIU/mL; 95 % CI = -8.49 to 0.14 µIU/mL; P = 0.06), preterm delivery (OR = 0.42; 95 % CI = 0.06 to 2.95; P = 0.38), macrosomia (OR = 0.34; 95 % CI = 0.08 to 1.35; P = 0.13) or BMI change (MD = -0.01 kg/m2; 95 % CI = -0.06 to 0.04 kg/m2; P = 0.63). CONCLUSIONS: Magnesium supplementation may be effective for the treatment of gestational diabetes without taking insulin treatment.

The Efficacy and Safety of Myo-inositol Supplementation for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Pregnant Women: A Systematic Review and Meta-Analysis.

Background: Myo-inositol has emerged as one of the preventive therapies for the development of gestational diabetes mellitus in at-risk populations. This systematic review and meta-analysis was conducted to determine the efficacy and safety of myo-inositol in decreasing the incidence of gestational diabetes in overweight and obese pregnant women. Methodology: This meta-analysis was conducted using the standard Cochrane methodology and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. Inclusion criteria were randomized controlled trials (RCTs) that enrolled overweight and obese pregnant women and used myo-inositol supplementation. The primary outcome was the incidence of gestational diabetes mellitus at 24-28 weeks. Secondary outcomes included cesarean section rate, the incidence of pregnancy-induced hypertension, macrosomia and preterm delivery. Risk ratios (RRs) and 95% confidence intervals (CIs) were used for dichotomous data. Results: Six RCTs were included. Compared to standard micronutrient supplementation, standard dose of myo-inositol (4 g) may reduce the incidence of GDM (RR 0.54; CI [0.30, 0.96]; n = 887 women), but the certainty of evidence is low to very low. With low-dose myo-inositol however, evidence is uncertain about its benefit on the incidence of gestational diabetes mellitus in overweight and obese women with RR 0.71; CI [0.14, 3.50]. No adverse effects were noted. For the secondary outcomes, standard dose myo-inositol appears to reduce the incidence of pregnancy-induced hypertension and preterm delivery, but the certainty of evidence is low to very low. Conclusion: Current evidence is uncertain on the potential benefit of myo-inositol supplementation in overweight and obese pregnant women. While studies show that 4 g myo-inositol per day may decrease the incidence of GDM, pregnancy-induced hypertension and pre-term birth with no associated risk of serious adverse events, the certainty of evidence is low to very low. Future high-quality trials may provide more compelling evidence to support practice recommendations.