Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring.

Gestational diabetes mellitus (GDM) is characterized by insulin resistance and low-grade inflammation, and most studies have demonstrated gut dysbiosis in GDM pregnancies. Overall, they were manifested as a reduction in microbiome diversity and richness, depleted short chain fatty acid (SCFA)-producing genera and a dominant of Gram-negative pathogens releasing lipopolysaccharide (LPS). The SCFAs functioned as energy substance or signaling molecules to interact with host locally and beyond the gut. LPS contributed to pathophysiology of diseases through activating Toll-like receptor 4 (TLR4) and involved in inflammatory responses. The gut microbiome dysbiosis was not only closely related with GDM, it was also vital to fetal health through vertical transmission. In this review, we summarized gut microbiota signature in GDM pregnancies of each trimester, and presented a brief introduction of microbiome derived SCFAs. We then discussed mechanisms of microbiome-host interactions in the physiopathology of GDM and associated metabolic disorders. Finally, we compared offspring microbiota composition from GDM with that from normal pregnancies, and described the possible mechanism.

The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta.

Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.

Discrete placental gene expression signatures accompany diabetic disease classifications during pregnancy.

BACKGROUND: Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle modifications) and gestational diabetes subtype A2 (GDMA2) (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear. OBJECTIVE: Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between preexisting type 2 and gestational diabetes subtypes would be associated with altered gene expression profiles in specific placental cell populations. STUDY DESIGN: In a large case-cohort design, we compared validated cases of GDMA1, GDMA2, and type 2 diabetes mellitus (T2DM) to healthy controls by bulk RNA-seq (n=54). Quantitative analyses with reverse transcription and quantitative PCR of presumptive genes of significant interest were undertaken in an independent and nonoverlapping validation cohort of similarly well-characterized cases and controls (n=122). Additional integrated analyses of term placental single-cell, single-nuclei, and spatial transcriptomics data enabled us to determine the cellular subpopulations and niches that aligned with the GDMA1, GDMA2, and T2DM gene expression signatures at higher resolution and with greater confidence. RESULTS: Dimensional reduction of the bulk RNA-seq data revealed that the most common source of placental gene expression variation was the diabetic disease subtype. Relative to controls, we found 2052 unique and significantly differentially expressed genes (-22 thresholds; q<0.05 Wald Test) among GDMA1 placental specimens, 267 among GDMA2, and 1520 among T2DM. Several candidate marker genes (chorionic somatomammotropin hormone 1 [CSH1], period circadian regulator 1 [PER1], phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [PIK3CB], forkhead box O1 [FOXO1], epidermal growth factor receptor [EGFR], interleukin 2 receptor subunit beta [IL2RB], superoxide dismutase 3 [SOD3], dedicator of cytokinesis 5 [DOCK5], suppressor of glucose, and autophagy associated 1 [SOGA1]) were validated in an independent and nonoverlapping validation cohort (q<0.05 Tukey). Functional enrichment revealed the pathways and genes most impacted for each diabetes subtype, and the degree of proximal similarity to other subclassifications. Surprisingly, GDMA1 and T2DM placental signatures were more alike by virtue of increased expression of chromatin remodeling and epigenetic regulation genes, while albumin was the top marker for GDMA2 with increased expression of placental genes in the wound healing pathway. Assessment of these gene signatures in single-cell, single-nuclei, and spatial transcriptomics data revealed high specificity and variability by placental cell and microarchitecture types. For example, at the cellular and spatial (eg, microarchitectural) levels, distinguishing features were observed in extravillous trophoblasts (GDMA1) and macrophages (GDMA2). Lastly, we utilized these data to train and evaluate 4 machine learning models to estimate our confidence in predicting the control or diabetes status of placental transcriptome specimens with no available clinical metadata. CONCLUSION: Consistent with the distinct association of perinatal outcome risk, placentae from GDMA1, GDMA2, and T2DM-affected pregnancies harbor unique gene signatures that can be further distinguished by altered placental cellular subtypes and microarchitectural niches.

Gestational diabetes mellitus is associated with in vivo platelet activation and platelet hyperreactivity.

BACKGROUND: Gestational diabetes mellitus is associated with obstetrical and long-term cardiovascular complications. Although platelet hyperresponsiveness in type-2 diabetes mellitus has been well characterized and has been shown to play a crucial role in cardiovascular complications, this aspect has been little studied in gestational diabetes mellitus. OBJECTIVE: We aimed to evaluate platelet reactivity, in vivo platelet activation, and endothelial function in gestational diabetes mellitus in comparison with normal pregnancy. STUDY DESIGN: This was a prospective, case-control study of 23 women with gestational diabetes mellitus and 23 healthy pregnant women who were studied at 26 to 28 and 34 to 36 weeks of gestation and at 8 weeks postpartum. Platelet reactivity and in vivo platelet activation, including light transmission aggregometry, PFA-100, platelet activation antigen expression, platelet adhesion under flow, platelet nitric oxide and reactive oxygen species production, and endothelial dysfunction markers, were assessed. RESULTS: The study of platelet function showed a condition of platelet hyperreactivity in cases with gestational diabetes mellitus when compared with healthy pregnant women at enrollment, which was further enhanced at the end of pregnancy and tended to decrease 2 months after delivery, although it still remained higher in gestational diabetes mellitus. In vivo platelet activation was also evident in gestational diabetes mellitus, especially at the end of pregnancy, in part persisting up to 8 weeks after delivery. Finally, women with gestational diabetes mellitus showed defective platelet nitric oxide production and endothelial dysfunction when compared with healthy pregnancies. CONCLUSION: Our data showed that gestational diabetes mellitus generates a condition of platelet hyperreactivity that in part persists up to 2 months after delivery. Impaired platelet sensitivity to nitric oxide and reduced platelet and endothelial nitric oxide production may contribute to the platelet hyperreactivity condition. Platelet hyperreactivity may play a role in the long-term cardiovascular complications of gestational diabetes mellitus women.

Vitronectin promotes insulin resistance in trophoblast cells by activating JNK in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common disorder in the clinic, which may lead to severe detrimental outcomes both for mothers and infants. However, the underlying mechanisms for GDM are still not clear. In the present study, we performed label-free proteomics using placentas from GDM patients and normal controls. Vitronectin caused our attention among differentially expressed proteins due to its potential role in the pathological progression of GDM. Vitronectin was increased in the placentas of GDM patients, which was confirmed by Western blot analysis. Vitronectin represses insulin signal transduction in trophoblast cells, whereas the knockdown of vitronectin further potentiates insulin-evoked events. Neutralization of CD51/61 abolishes the repressed insulin signal transduction in vitronectin-treated trophoblast cells. Moreover, vitronectin activates JNK in a CD51/61-depedent manner. Inhibition of JNK rescues impaired insulin signal transduction induced by vitronectin. Overall, our data indicate that vitronectin binds CD51/61 in trophoblast cells to activate JNK, and thus induces insulin resistance. In this regard, increased expression of vitronectin is likely a risk factor for the pathological progression of GDM. Moreover, blockade of vitronectin production or its receptors (CD51/61) may have therapeutic potential for dealing with GDM.

The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. OBJECTIVES: We aimed to assess the association between preconception cannabis use and GDM incidence. METHODS: We analysed individual-level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual-level data, we used logistic regression to estimate study-type-specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta-analysis to combine study-type-specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre-pregnancy body mass index (BMI). RESULTS: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. CONCLUSIONS: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications.

Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

A cost-effectiveness evaluation of a dietitian-delivered telephone coaching program during pregnancy for preventing gestational diabetes mellitus.

BACKGROUND: This study aimed to evaluate the cost-effectiveness of a telehealth coaching intervention to prevent gestational diabetes mellitus (GDM) and to calculate the breakeven point of preventing GDM. METHODS: Data to inform the economic evaluation model was sourced directly from the large quaternary hospital in Brisbane, where the Living Well during Pregnancy (LWdP) program was implemented, and further supplemented with literature-based estimates where data had not been directly collected in the trial. A cost-effectiveness model was developed using a decision tree framework to estimate the potential for cost savings and quality of life improvement. A total of 1,315 pregnant women (49% with a BMI 25-29.9, and 51% with a BMI ≥ 30) were included in the analyses. RESULTS: The costs of providing routine care and routine care plus LWdP coaching intervention to pregnant women were calculated to be AUD 20,933 and AUD 20,828, respectively. The effectiveness of the LWdP coaching program (0.894 utility) was slightly higher compared to routine care (0.893). Therefore, the value of the incremental cost-effectiveness ratio (ICER) was negative, and it indicates that the LWdP coaching program is a dominant strategy to prevent GDM in pregnant women. We also performed a probabilistic sensitivity analysis using Monte Carlo simulation through 1,000 simulations. The ICE scatter plot showed that the LWdP coaching intervention was dominant over routine care in 93.60% of the trials using a willingness to pay threshold of AUD 50,000. CONCLUSION: Findings support consideration by healthcare policy and decision makers of telehealth and broad-reach delivery of structured lifestyle interventions during pregnancy to lower short-term costs associated with GDM to the health system.

METTL14-mediated lncRNA XIST silencing alleviates GDM progression by facilitating trophoblast cell proliferation and migration via the miR-497-5p/FOXO1 axis.

Gestational diabetes mellitus (GDM), a prevalent complication during the gestation period, has been linked to impaired proliferation and migration of trophoblasts causing placental maldevelopment. We previously found that lncRNA X-inactive specific transcript (XIST) played an essential role in GDM progression. Here, we investigated the precise biological functions as well as the upstream and downstream regulatory mechanisms of XIST in GDM. We found that XIST and forkhead box O1 (FOXO1) were conspicuously upregulated and miR-497-5p and methyltransferase-like 14 (METTL14) were downregulated in the placentas of GDM patients. XIST silencing facilitated proliferation and migration and inhibited cell apoptosis and cell cycle arrest in HG-cultured HTR8/SVneo cells. METTL14 inhibited XIST expression through m6A methylation modification. XIST overexpression abrogated the positive effect of METTL14 overexpression on HG-cultured HTR8/SVneo cell progression. MiR-497-5p and FOXO1 are downstream regulatory genes of XIST in HTR8/SVneo cells. Reverse experiments illustrated that XIST mediated HTR8/SVneo cell functions by regulating the miR-497-5p/FOXO1 axis. Additionally, XIST silencing augmented glucose tolerance and alleviated fetal detrimental changes in GDM rats. To conclude, METTL14-mediated XIST silencing facilitated proliferation and migration and inhibited cell apoptosis and cell cycle arrest in HG-cultured HTR8/SVneo cells via the miR-497-5p/FOXO1 axis, thereby alleviating GDM progression in rats.

Association of exposure to multiple heavy metals during pregnancy with the risk of gestational diabetes mellitus and insulin secretion phase after glucose stimulation.

BACKGROUND: Epidemiological evidence for the association between heavy metals exposure during pregnancy and gestational diabetes mellitus (GDM) is still inconsistent. Additionally, that is poorly understood about the potential cause behind the association, for instance, whether heavy metal exposure is related to the change of insulin secretion phase is unknown. OBJECTIVES: We aimed to explore the relationships of blood levels of arsenic (As), lead (Pb), thallium (Tl), nickel (Ni), cadmium (Cd), cobalt (Co), barium (Ba), chromium (Cr), mercury (Hg) and copper (Cu) during early pregnancy with the odds of GDM, either as an individual or a mixture, as well as the association of the metals with insulin secretion phase after glucose stimulation. METHODS: We performed a nested case-control study consisting of 302 pregnant women with GDM and 302 controls at the First Affiliated Hospital of Anhui Medical University in Hefei, China. Around the 12th week of pregnancy, blood samples of pregnant women were collected and levels of As, Pb, Tl, Ni, Cd, Co, Ba, Cr, Hg and Cu in blood were measured. An oral glucose tolerance test (OGTT) was done in each pregnant woman during the 24-28th week of pregnancy to diagnose GDM and C-peptide (CP) levels during OGTT were measured simultaneously. The four metals (As, Pb, Tl and Ni) with the highest effect on odds of GDM were selected for the subsequent analyses via the random forest model. Conditional logistic regression models were performed to analyze the relationships of blood As, Pb, Tl and Ni levels with the odds of GDM. The weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR) were used to assess the joint effects of levels of As, Pb, Tl and Ni on the odds of GDM as well as to evaluate which metal level contributed most to the association. Latent profile analysis (LPA) was conducted to identify profiles of glycemic and C-peptide levels at different time points. Multiple linear regression models were employed to explore the relationships of metals with glycaemia-related indices (fasting blood glucose (FBG), 1-hour blood glucose (1h BG), 2-hour blood glucose (2h BG), fasting C-peptide (FCP), 1-hour C-peptide (1h CP), 2-hour C-peptide (2h CP), FCP/FBG, 1h CP/1h BG, 2h CP/2h BG, area under the curve of C-peptide (AUCP), area under the curve of glucose (AUCG), AUCP/AUCG and profiles of BGs and CPs, respectively. Mixed-effects models with repeated measures data were used to explore the relationship between As (the ultimately selected metal) level and glucose-stimulated insulin secretion phase. The mediation effects of AUCP and AUCG on the association of As exposure with odds of GDM were investigated using mediation models. RESULTS: The odds of GDM in pregnant women increased with every ln unit increase in blood As concentration (odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.04-2.05). The joint effects of As, Pb, Tl and Ni levels on the odds of GDM was statistically significant when blood levels of four metals were exceeded their 50th percentile, with As level being a major contributor. Blood As level was positively associated with AUCG and the category of glucose latent profile, the values of AUCG were much higher in GDM group than those in non-GDM group, which suggested that As exposure associated with the odds of GDM may be due to that As exposure was related to the impairment of glucose tolerance among pregnant women. The significant and positive relationships of As level with AUCP, CP latent profile category, 2h CP and 2h CP/2h BG were observed, respectively; and the values of 1h CP/1h BG and AUCP/AUCG were much lower in GDM group than those in non-GDM group, which suggested that As exposure may not relate to the impairment of insulin secretion (pancreatic ß-cell function) among pregnant women. The relationships between As level and 2h CP as well as 2h CP/2h BG were positive and significant; additionally, the values of 2h CP/2h BG in GDM group were comparable with those in non-GDM group; the peak value of CP occurred at 2h in GDM group, as well as the values of 2h CP/2h BG in high As exposure group were much higher than those in low As exposure group, which suggested that As exposure associated with the increased odds of GDM may be due to that As exposure was related to the change of insulin secretion phase (delayment of the peak of insulin secretion) among pregnant women. In addition, AUCP mediated 11% (p < 0.05) and AUCG mediated 43% (p < 0.05) of the association between As exposure and the odds of GDM. CONCLUSION: Our results suggested that joint exposure to As, Pb, Tl and Ni during early pregnancy was positively associated with the odds of GDM, As was a major contributor; and the association of environmental As exposure with the increased odds of GDM may be due to that As exposure was related to the impairment of glucose tolerance and change of insulin secretion phase after glucose stimulation (delayment of the peak of insulin secretion) among pregnant women.

Association between exposure to outdoor artificial light at night during pregnancy and glucose homeostasis: A prospective cohort study.

BACKGROUND: Outdoor artificial light at night (ALAN) has been linked to an elevated risk of diabetes, but the available literature on the relationships between ALAN and glucose homeostasis in pregnancy is limited. METHODS: A prospective cohort study of 6730 pregnant women was conducted in Hefei, China. Outdoor ALAN exposure was estimated using satellite data with individual addresses at a spatial resolution of approximately 1 km, and the average ALAN intensity was calculated. Gestational diabetes mellitus (GDM) was diagnosed based on a standard 75-g oral glucose tolerance test. Multivariable linear regression and logistic regression were used to estimate the relationships between ALAN and glucose homeostasis. RESULTS: Outdoor ALAN was associated with elevated glucose homeostasis markers in the first trimester, but not GDM risk. An increase in the interquartile range of outdoor ALAN values was related to a 0.02 (95% confidence interval [CI]: 0.00, 0.03) mmol/L higher fasting plasma glucose, a 0.42 (95% CI: 0.30, 0.54) µU/mL increase in insulin and a 0.09 (95% CI: 0.07, 0.12) increase in homeostatic model assessment of insulin resistance (HOMA-IR) during the first trimester. Subgroup analyses showed that the associations between outdoor ALAN exposure and fasting plasma glucose, insulin, and HOMA-IR were more pronounced among pregnant women who conceived in summer and autumn. CONCLUSIONS: The results provided evidence that brighter outdoor ALAN in the first trimester was related to elevated glucose intolerance in pregnancy, especially in pregnant women conceived in summer and autumn, and effective strategies are needed to prevent and manage light pollution.

Gestational Diabetes Mellitus and Metabolic Syndrome: A Review of the Associations and Recommendations.

OBJECTIVE: Gestational diabetes mellitus (GDM) and metabolic syndrome (MetS) share common characteristics and risk factors. Both conditions increase the risk of chronic diseases and, thus, may share a common pathogenesis. This review begins with a clinical vignette, followed by evidence supporting the risk of MetS after GDM among women and their offspring and the risk of having GDM among pregnant women who have MetS before pregnancy. METHODS: Research studies published between 2010 and 2023 were identified via several databases, including PubMed, the Web of Science, MEDLINE, Science Direct, ERIC, and EBSCOhost. Search terms included gestational diabetes and metabolic syndrome. Reviews, books/e-books, patents, news, trade publications, reports, dissertations/theses, conference materials, and articles in non-English languages were all excluded. RESULTS: MetS increases not only the incidence of GDM during pregnancy but also the risk of diabetes in women with a history of GDM. On the other hand, women with a history of GDM had an almost 4 times increased risk of developing MetS at minimum of 1 year after delivery, and the risk increases with longer time lapse since the index pregnancy. Prepregnancy body mass index appears to be the strongest factor predicting MetS. Children exposed to GDM in utero have at least a 2 times increased risk of MetS in later life. CONCLUSION: Timely assessment and continuing surveillance of MetS before and after pregnancy followed by GDM are recommended. Weight management and nutrition counseling are of importance to reduce the risk of GDM and MetS among pregnant women.

The potential causal effect of the pre-pregnancy dietary phytochemical index on gestational diabetes mellitus: a prospective cohort study.

BACKGROUND: Phytochemicals are non-nutritive bioactive compounds with beneficial effects on the metabolism of glucose. This study aimed to clarify the possible causal effect of the pre-pregnancy dietary phytochemical index (DPI) on gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study 1,856 pregnant women aged 18-45 years who were in their first trimester, were recruited and followed up until delivery. The dietary intakes of participants were examined using an interviewer-administered validated 168-item semi-quantitative food frequency questionnaire (FFQ). Inverse probability weighting (IPW) of propensity scores (PS), estimated from the generalized boosted model (GBM) were used to obtain a adjusted risk ratio (aRR) for potential confounders. RESULTS: During the follow-up period, 369 (19.88%) women were diagnosed with GDM. DPI scores ranged from 6.09 to 89.45. There was no association between DPI scores and GDM (aRR: 1.01, 95% confidence interval [CI]: 0.92, 1.08; p trend = 0.922). When comparing DPI quartile 4 (most pro-phytochemical content) to quartile 1 (few phytochemical contents), there was no significant difference between them (aRR: 0.97; 95% CI: 0.75, 1.25; p = 0.852). Also, there was no significant difference between DPI quartile 3 and quartile 1 (aRR: 1.04; 95% CI: 0.81, 1.34; p = 0.741) as well as DPI quartile 2 and quartile 1 (aRR: 0.92; 95% CI: 0.71, 1.21; p = 0.593). CONCLUSIONS: Although this data did not support the association between pre-pregnancy DPI scores and GDM, further cohort studies to ascertain the causal association between them are warranted.

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

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

Predictive factors of perinatal depression among women with gestational diabetes mellitus in the UAE: a cross-sectional clinical study.

BACKGROUND: Gestational Diabetes Mellitus (GDM) is responsible for the development of 30-50% of type 2 diabetes mellitus that predisposes later to adverse consequences among affected mothers and their offspring. Several studies have suggested that GDM increases the risk of developing perinatal depression (PND); however, factors that are involved in this association are yet to be determined. This study aims to identify factors that interrelate GDM and PND among pregnant and postnatal women in the United Arab Emirates (UAE). METHODS: A total of 186 women between 18 and 45 years old attending the obstetrics clinic during their 3rd trimester or up to 6 months postnatal were recruited between October 2021 and April 2022. Women who were known to have pre-existing diabetes mellitus (type 1 or type 2), kidney disease, liver disease, and those receiving hormonal therapy were excluded. Participants completed a structured questionnaire including sociodemographic data and the Edinburgh Postnatal Depression Scale (EPDS). Based on their EPDS scores, study participants were categorized into three groups: no depression (> 9), possible depression (9-11), and high possibility/strong positive depression (≥ 12). SPSS 26 was used for data analysis. RESULTS: Among the 186 participants, 81% (n = 151) were Emirati, 41% (n = 76) had no GDM, and 58% (n = 110) had GDM. Of the study participants, 34.4% had a high possibility of strong positive depression, 40.9% had possible depression, and only 6.5% had no depression. The association between GDM and PND was clinically and statistically insignificant, with a calculated odds ratio (OR) of 1.574 (p value = 0.204) and a 95% confidence interval (0.781-3.172). However, age, personal history of depression, and BMI were found to be strong predictors of depression among pregnant/postpartum women in the UAE. CONCLUSIONS: The study findings propose that age, personal history of depression, and obesity are strong predictors of depression during pregnancy. The strong correlation between obesity (which is a known strong predictor of GDM) and PND suggests that further studies with longitudinal designs and longer observational periods might better reveal the relationship between GDM and PND. TRIAL REGISTRATION: Retrospectively registered study by Research Ethics Committees of the University Hospital Sharjah and the University of Sharjah (Ref. No.: UHS-HERC- 025-17122019) December 17, 2019.

Serum Glycome as a Diagnostic and Prognostic Factor in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a risk factor for both mother and fetus/neonate during and after the pregnancy. Inconsistent protocols and cumbersome screening procedures warrant the search for new and easily accessible biomarkers. We investigated a potential of serum N-glycome to differentiate between healthy pregnant women (n = 49) and women with GDM (n = 53) using a lectin-based microarray and studied the correlation between the obtained data and parameters of glucose and lipid metabolism. Four out of 15 lectins used were able to detect the differences between the control and GDM groups in fucosylation, terminal galactose/N-acetylglucosamine (Gal/GlcNAc), presence of Galα1,4Galß1,4Glc (Gb3 antigen), and terminal α2,3-sialylation with AUC values above 60%. An increase in the Gb3 antigen and α2,3-sialylation correlated positively with GDM, whereas the amount of fucosylated glycans correlated negatively with the content of terminal Gal/GlcNAc. The content of GlcNAc oligomers correlated with the highest number of blood analytes, indices, and demographic characteristics, but failed to discriminate between the groups. The presence of terminal Gal residues correlated positively with the glucose levels and negatively with the LDL levels in the non-GDM group only. The results suggest fucosylation, terminal galactosylation, and the presence of Gb3 antigen as prediction markers of GDM.

Effect of arsenic on the risk of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a complication of pregnancy associated with numerous adverse outcomes. There may be a potential link between GDM and arsenic (As) exposure, but this hypothesis remains controversial. This meta-analysis summarizes the latest studies evaluating the association between As and GDM. METHODS: A comprehensive search of the PubMed, Embase, and Scopus databases up to September 2023 was performed. The pooled estimates with 95% CIs were presented using forest plots. Estimates were calculated with random effects models, and subgroup and sensitivity analyses were conducted to address heterogeneity. RESULTS: A total of 13 eligible studies involving 2575 patients with GDM were included in this meta-analysis. The results showed that women exposed to As had a significantly increased risk of GDM (OR 1.47, 95% CI: 1.11 to 1.95, P = 0.007). Subgroup analyses suggested that the heterogeneity might be attributed to the years of publication. In addition, sensitivity analysis confirmed the robust and reliable results. CONCLUSIONS: This analysis suggested that women exposed to As have a greater risk of GDM. However, the significant heterogeneity across studies requires careful interpretation. REGISTRATION: The PROSPERO registration ID is CRD42023461820.

Effect of probiotics on pregnancy outcomes in gestational diabetes: systematic review and meta-analysis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a prevalent complication during pregnancy associated with numerous adverse outcomes. There is emerging evidence suggesting the potential of probiotics as a therapeutic measure for GDM; however, existing studies have yielded contradictory results. This meta-analysis assessed the efficacy of probiotics on blood glucose management and pregnancy outcomes in patients with GDM. METHODS: A comprehensive search of the PubMed, Embase, and Cochrane databases was conducted up to August 22, 2023, to identify relevant studies. The primary outcomes focused on fasting blood glucose (FBG), fasting serum insulin (FSI), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). The secondary outcomes included various maternal and neonatal outcomes. RESULTS: This meta-analysis included 15 randomized controlled trials (RCTs), encompassing 1006 patients with GDM. The results showed that, compared to a placebo, probiotics demonstrated a significant reduction in FBG (MD - 2.58, 95% CI - 4.38 to - 0.79, p < 0.01), FSI (MD - 2.29, 95% CI - 3.40 to - 1.18, p < 0.01), HOMA-IR (MD - 0.56, 95% CI - 0.81 to - 0.32, p < 0.01), and birth weight (MD - 101.20, 95% CI - 184.62 to - 17.77, p = 0.02). Furthermore, it resulted in fewer neonatal intensive care unit (NICU) admissions (RR 0.60, 95% CI 0.40-0.89, p = 0.01), instances of hyperbilirubinemia (RR 0.31, 95% CI 0.16-0.61, p < 0.01), and elevated QUICKI (MD 0.01, 95% CI 0.00-0.01, p < 0.01). No significant impact was observed in the other analyzed outcomes. CONCLUSIONS: In conclusion, probiotics improve FBG, FSI, and HOMA-IR, and reduce the occurrence of neonatal hyperbilirubinemia, NICU admissions, and birth weight in the offspring of patients with GDM. However, the quality of the evidence, as per the GRADE approach, varies from high to low, necessitating further studies to consolidate these findings.

Does the gestational age at which the glucose challenge test (GCT) is conducted influence the diagnosis of gestational diabetes mellitus (GDM)?

PURPOSE: This study's objective is to investigate disparities in the rates of gestational diabetes mellitus (GDM) diagnosis, influenced by the timing of the glucose challenge test GCT. METHODS: This retrospective cohort study included women with singleton or twin pregnancies exhibiting abnormal GCT result between 24 and 28 weeks of gestation, followed by an oral glucose tolerance test OGTT during the same period. Data regarding pregnancy follow-up from patients' deliveries at a singular tertiary medical from 2014 to 2022 were retrieved. The probability of GDM diagnosis was stratified based on the gestational week of the GCT and the definition of a positive OGTT, delineated by one or two abnormal values. RESULTS: The study included 636 women with abnormal GCT between 24 and 28 weeks of gestation. Of them, 157 unerwent the GCT between 24.0 and 24.6 weeks, 204 between 25.0 and 25.6 weeks, 147 between 26.0 and 26.6 weeks, and 128 between 27.0 and 28.6 weeks. We found that the highest incidence of GDM, defined by one or two pathological values of the OGTT, following the initial screening with a GCT, where abnormal results were defined as values exceeding 140 mg/dL, was diagnosed in patients who underwent GCT between 26.0 and 26.6 weeks of gestation. Conversely, the lowest rates were observed in patients screened between 24.0 and 24.6 weeks of gestation. CONCLUSION: The timing of screening for GDM using the GCT significantly affects the rate of diagnosis. Clinicians managing pregnancies should consider this data when formulating treatment plans.

Does the combination of four OGTT values enhance the prediction of adverse pregnancy outcomes? Insights from a retrospective cohort study.

AIM: To explore the correlation between a singular value of additive OGTT scores and adverse maternal and neonatal outcomes. We postulated that a higher additive OGTT score would predict poorer maternal and neonatal outcomes. METHODS: In this retrospective cohort study, data were collected from all women with a documented complete OGTT result and subsequent diagnosis of GDM. The additive OGTT score was calculated by adding each individual hourly glucose measurement. Maternal demographics, pregnancy and labor characteristics, and neonatal outcomes were compared between the lower-sum and higher-sum OGTT groups. A multivariate regression analysis was performed to identify confounders associated with adverse outcomes. RESULTS: In this study, a total of 1497 patients were assessed. The group with higher-sum OGTT scores was characterized by increased rates of GDMA2 (p = 0.008), higher insulin doses (p = 0.009), and higher rates of composite maternal and neonatal adverse outcomes (p = 0.021 and p = 0.030, respectively) compared to the lower-sum OGTT group. CONCLUSION: The additive OGTT score may aid in predicting the need for insulin treatment, labor course, and neonatal outcomes in GDM patients.