Search Results (1,695)

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of obesity and type 2 diabetes, particularly among women of reproductive age. Emerging evidence suggests potential effects on ovulation, fertility, and pregnancy outcomes. This narrative review aims to synthesize current evidence on the reproductive safety of GLP-1RAs, with a focus on their implications for conception, unintended pregnancy, and maternal–fetal outcomes. Methods: A narrative literature review was conducted using PubMed and relevant bibliographic sources to identify studies published between 2020 and 2025. The search included clinical trials, observational studies, registry data, case reports, and selected preclinical evidence. Studies addressing reproductive outcomes, including ovulation, fertility, pregnancy exposure, and fetal safety, were included. Evidence was synthesized descriptively in accordance with recommended approaches for narrative reviews. Results: Available evidence indicates that GLP-1RAs may improve ovulatory function and menstrual regularity, particularly in women with obesity or polycystic ovary syndrome, potentially increasing the likelihood of conception. However, human data on pregnancy exposure remain limited. While current evidence does not consistently demonstrate a strong teratogenic signal, findings are based on small samples and heterogeneous study designs. Concerns persist regarding unintended pregnancies due to improved fertility and the absence of robust safety data during early gestation. Conclusions: GLP-1RAs present a complex clinical scenario in women of reproductive age, with potential benefits for metabolic and reproductive health but uncertain safety during pregnancy. Clinicians should exercise caution, provide appropriate contraceptive counseling, and carefully weigh the risks and benefits when prescribing these agents. Further large-scale, prospective studies are needed to clarify reproductive safety and inform evidence-based clinical guidelines. Full article

Background: Postpartum oral glucose tolerance test (OGTT) screening after gestational diabetes mellitus (GDM) enables early detection and prevention of type 2 diabetes, yet adherence is suboptimal, particularly in regional and rural areas. This study examined lifestyle behaviour and health-related quality-of-life factors associated with OGTT non-adherence over time. Methods: A longitudinal cohort study of women with prior GDM in regional and rural New South Wales, Australia, was conducted. Binary logistic regression models examined associations between lifestyle behaviours, health-related quality of life, and OGTT non-adherence at 3, 18, and 36 months postpartum. Results: OGTT non-adherence increased over time. Multivariable models were not statistically significant at any timepoint. At 3 months postpartum, several lifestyle and health-related quality-of-life variables were associated with non-adherence; however, these associations were not sustained at later timepoints. No consistent predictors of non-adherence were identified across follow-up. Conclusions: All women with prior GDM remain at risk of missed postpartum screening, with engagement declining over time. Findings should be interpreted as exploratory, reflecting time-specific patterns rather than stable predictors. Early postpartum represents a critical window for intervention, while longer-term strategies require flexible, integrated, and accessible models of care to support sustained diabetes prevention, particularly in regional and rural populations. Full article

This study aimed to investigate whether mixed heavy metal exposure (lead, cadmium, manganese, and arsenic) during pregnancy induces gestational diabetes mellitus (GDM)-like phenotypes and to explore the associated molecular alterations. We examined the effects of exposure on metabolic disturbances using a Sprague-Dawley rat model exposed to low- and high-dose mixed heavy metals, with doses selected based on biomonitoring data. The results showed that high-dose mixed heavy metal exposure significantly increased blood glucose levels in rats, elevated the area under the curve (AUC) during the oral glucose tolerance test (OGTT), and induced insulin resistance and dyslipidemia. Concurrently, pathological examinations revealed hepatocyte steatosis, inflammatory cell infiltration, and mitochondrial abnormalities in liver tissues. Transcriptomic and metabolomic analyses identified significant disruption of the glycerophospholipid metabolic pathway following heavy metal exposure, suggesting the involvement of this pathway in the observed metabolic disturbances. Lasso regression analysis identified Insig1 as a candidate gene associated with lipid metabolic alterations, a finding subsequently validated by qPCR. Overall, mixed heavy metal exposure during pregnancy was associated with GDM-like metabolic abnormalities in rats. Disruption of glycerophospholipid metabolism and altered Insig1 expression likely contribute to these effects, providing molecular evidence linking mixed heavy metal exposure to gestational metabolic dysfunction. Full article

Diabetes and related metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD), are increasingly recognized as diseases of inter-organ metabolic dysregulation rather than disorders of a single organ. The core of this process is the liver–pancreas axis, which integrates metabolic signals to maintain glucose and lipid homeostasis. Under physiological conditions, insulin and glucagon work together to regulate glucose production in the liver. The liver, in turn, regulates pancreatic β-cell function through hepatokines, metabolites and extracellular vesicles. Axis disorder driven by liver insulin resistance, lipid accumulation, inflammation or changes in hepatokine secretion exacerbates β-cell dysfunction, glucotoxicity and lipotoxic stress, thereby accelerating disease progression. This imbalance is involved in the pathogenesis of type 2 diabetes, type 1 diabetes, gestational diabetes, and monogenic diabetes, and makes MASLD a driving factor and early predictor of diabetes onset. This review summarizes the key molecular mechanisms behind liver–pancreas crosstalk and explores potential therapeutic strategies aimed at restoring coordinated metabolic regulation between the organs. Full article

Obesity in women of reproductive age is a major issue. It is associated with reduced fertility and an increased risk of obstetric and perinatal complications. Bariatric surgery is the most effective treatment for severe obesity, leading to substantial weight reduction, improvement of metabolic disorders, and enhanced fertility. Consequently, an increasing number of women are becoming pregnant after undergoing bariatric surgery. The aim of this paper is to review current recommendations and research data regarding the care of women after bariatric surgery in the periconceptional and perinatal periods, as well as throughout pregnancy, delivery, and the postpartum period. Research suggests that pregnancy after bariatric surgery is associated with a lower risk of gestational diabetes, hypertension, preeclampsia, and fetal macrosomia compared with pregnancies in women with similar baseline BMI (body mass index) who have not undergone surgical treatment. At the same time, an increased risk is observed for low birth weight, maternal micro- and macronutrient deficiencies, and complications characteristic of bariatric procedures, such as dumping syndrome or intra-abdominal hernias. Most scientific societies recommend postponing pregnancy planning for 12–18 months after surgery and using effective contraception, preferably methods that do not require gastrointestinal absorption. Regular monitoring of laboratory parameters, individually tailored supplementation, and interdisciplinary care are essential for the safe management of pregnancy after bariatric surgery. In particular, care should include achieving a stable body weight before conception, monitoring of nutritional status, verifying proper weight gain during pregnancy, and considering alternative methods for gestational diabetes screening (e.g., glycaemic monitoring instead of oral glucose tolerance testing) due to the risk of dumping syndrome. Appropriate preparation for pregnancy and proper management throughout its course allow for reducing the risk of perinatal complications. Bariatric surgery itself is not a contraindication to vaginal delivery. Full article

The link between neurodevelopment in infants exposed to maternal gestational diabetes mellitus (GDM) and fetal DNA methylation remains unexplored. We conducted this hypothesis-generating study to investigate the association between fetal DNA methylation and neurodevelopmental outcomes in children of mothers with GDM. We carried out a prospective, observational pilot cohort study comparing infants exposed to maternal GDM with an unexposed control group. Umbilical cord blood DNA methylation was assessed using targeted methylome sequencing covering 3.34 million CpG sites. Infant neurodevelopment was evaluated at age two years using the Bayley-III Scales. Bioinformatics processing identified differentially methylated regions (DMRs), followed by multiple enrichment analyses of DMR-associated genes and partial correlation analyses. Multi-dimensional enrichment analysis of the 1053 identified DMR-associated genes revealed a significant convergence of pathways related to neurogenesis, synaptic components, and axonal guidance. Infants born to mothers with GDM exhibited lower scores in cognitive, language, and motor domains, which were associated with identifiable DNA methylation signatures at birth. Significant correlations were observed in genes essential for brain scaffolding and synaptic circuitry, most notably WNT4, the PCDHG alpha/beta clusters, and PALM. Additionally, methylation patterns in FOXF2 and CHFR suggest a potential impact on blood–brain barrier integrity, while associations with FSTL3 and H6PD highlight a systemic metabolic ‘cross-talk’ influencing neurodevelopment. Although these pilot findings are hypothesis-generating and require further functional validation, this study provides pioneering evidence that neurodevelopmental alterations in the offspring of mothers with GDM are potentially associated with intrauterine epigenetic modifications detectable at birth. Full article

Background/Objectives: Continuous glucose monitoring (CGM) has transformed diabetes management by enabling high-resolution assessment of glucose dynamics, with well-established use in type 1 diabetes (T1D) and insulin-treated type 2 diabetes (T2D), and expanding applications across broader populations, including non-insulin-treated T2D and gestational diabetes. However, real-world implementation remains constrained by economic barriers, fragmented reimbursement, workflow challenges, and limited capacity for continuous data interpretation. This review examines key barriers to CGM implementation and synthesizes current evidence on pharmacist-integrated CGM care as an emerging model to support CGM adoption across clinical and community-based settings. Methods: A narrative literature review was conducted to synthesize evidence on pharmacist-integrated CGM services in diabetes care. Literature was identified through structured searches of PubMed, Embase, and the Cochrane Library, supplemented by Google Scholar and citation tracking, covering publications from January 2010 to December 2025. Studies were selected based on predefined criteria, including those reporting clinical outcomes, pharmacist involvement, or health system and implementation factors related to CGM use. Relevant survey-based and real-world studies were also considered to capture healthcare professionals’ perspectives and implementation experiences. Evidence was synthesized thematically across clinical, behavioral, and health system domains. Results: Available evidence suggests that pharmacist-integrated CGM care is associated with improvements in glycemic management, including increased time in range, reduced glycemic variability, and more timely pharmacotherapy optimization. Pharmacist involvement may also support patient education, self-management, and engagement with digital health technologies, and facilitate ongoing data interpretation and treatment adjustment between clinical encounters. However, evidence remains heterogeneous and geographically limited, with predominantly retrospective and pilot studies and few randomized trials, constraining the robustness and external validity of the findings. Further studies are needed to confirm its clinical effectiveness, comparative effectiveness, and economic value. Conclusions: Pharmacist-integrated CGM represents a promising and operationally feasible approach to supporting CGM use in routine diabetes care. While current evidence indicates potential benefits in glycemic management and care delivery processes, further research and implementation efforts are required to support its effective and sustainable adoption across diverse healthcare settings. Full article

Background/Objective: RNA modifications, including N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), 7-methylguanosine (m⁷G), N¹-methyladenosine (m¹A), pseudouridine (Ψ), N⁴-acetylcytidine (ac⁴C), 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U) and adenosine-to-inosine (A-to-I) editing, constitute a critical layer of post-transcriptional regulation that influences RNA stability, splicing, translation and degradation. This review aims to systematically summarise the current understanding of the molecular mechanisms and regulatory networks of RNA modifications in the female reproductive physiology and to evaluate their pathological implications in obstetric and gynaecologic disorders. Methods: We conducted a comprehensive literature review, synthesising findings from high-throughput sequencing studies, functional experiments and clinical investigations. The review integrates evidence across multiple RNA modification types, their regulatory enzymes (writers, erasers and readers) and their roles in physiological processes (germ cell development, oocyte maturation, embryogenesis and endometrial function) and pathological conditions (gynaecologic cancers, preeclampsia, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). Results: RNA modifications function as dynamic and reversible regulators that orchestrate key reproductive events, including primordial germ cell differentiation, oocyte meiosis, the maternal-to-zygotic transition, the establishment of uterine receptivity, and placental development. These modifications operate through coordinated writer–eraser–reader networks that fine tune transcripts’ stability, translation efficiency and RNA decay. The dysregulation of these epitranscriptomic networks is strongly implicated in the pathogenesis of gynaecologic malignancies (cervical, ovarian, endometrial cancers and choriocarcinoma), pregnancy-related disorders (preeclampsia, gestational diabetes mellitus and recurrent miscarriage), reproductive endocrine disorders (polycystic ovary syndrome and premature ovarian insufficiency) and benign gynaecological conditions (endometriosis and adenomyosis). Emerging evidence also reveals complex crosstalk among RNA modifications, such as cooperative interactions between m⁶A and m⁵C in translation regulation and antagonistic relationships between m⁶A and A-to-I editing. Conclusions: RNA modifications represent an essential and multifaceted regulatory layer in female reproduction, with broad implications for disease pathogenesis. Their unique reversibility and context-dependent functions offer promising opportunities for the development of diagnostic biomarkers and targeted therapeutic interventions. Future researchers should prioritise integrated multi-omics approaches, enhanced human-relevant models and clinical translation to fully realise the potential of epitranscriptomic medicine in reproductive health. Full article

Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article

Background/Objectives: Appetite-regulating hormones are bioactive components of human milk. We tested the associations of leptin and adiponectin with infant growth and eating behaviors to age 6 months. Methods: In a cohort of 70 healthy, full-term infants and their mothers, human milk adiponectin and leptin were assayed at age 2 months (m). At infant ages 2, 4, and 6 m, infant anthropometry was obtained, mothers reported feeding frequency, duration, and breastfeeding intensity and completed the Baby Eating Behavior Questionnaire (Enjoyment of Food, Food Responsiveness, and General Appetite), and infant sucking vigor using an artificial nipple (burst duration and sucking frequency) was measured. Mothers reported demographics, gestational diabetes and pre-pregnancy body mass index (BMI), gestational age, and infant birthweight. Multivariate models evaluated predictors of leptin and adiponectin, and associations of leptin and adiponectin with infant growth and eating behaviors. Results: Human milk leptin was predicted by maternal BMI (β = 0.02) and breastfeeding intensity (β = −0.32). Regarding infant growth, infant weight-for-age and weight-for-length z-scores at 6 m were predicted by leptin (β = 0.91 and β = 1.22, respectively) and adiponectin (β = 0.01 and β = 0.01, respectively). Regarding infant eating behaviors, feeding duration at 2 m and feeding frequency at 4 m were predicted by adiponectin (β = 0.03 and β = −0.02, respectively). Conclusions: Human milk leptin and adiponectin may contribute to weight gain in early infancy, but the effect does not appear to be mediated substantially by infant eating behaviors. Further investigation into the metabolic programming of early infant weight gain is warranted. Full article

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder associated with adverse maternal and fetal outcomes. However, current diagnostic strategies have a limited capacity to identify women at risk early in pregnancy. In this longitudinal prospective pilot study, 200 pregnant Mexican women were recruited at 11–14 weeks and underwent follow-up throughout pregnancy. Of these, 34 women (19 with GDM and 15 with normal glucose tolerance [NGT]) completed follow-up and were included in the final analyses. Most withdrawals were due to logistical constraints, although the reduced final sample size should be considered when interpreting generalizability. Nine serum proteins (ADIPOQ, AFM, FABP4, IGFBP-5, PAPP-A, PAPP-A2, RBP4, RETN, SHBG) were measured simultaneously using an antibody array and subsequently validated by ELISA. FABP4 showed the greatest increase in the first trimester (4.9-fold, p = 0.0105) and the highest apparent discriminative performance (AUC = 0.91), which declined in the second and third trimesters. Exploratory, hypothesis-generating multivariable analyses suggested a stronger association when FABP4 was combined with gravidity and serum triglycerides (AUC up to 0.97). Overall, FABP4 emerged as a promising candidate biomarker for early GDM detection in Mexican women; however, these findings are preliminary and require validation in larger, independent cohorts to support early risk stratification. Full article

The role of amino acid disturbances in the mother–fetus system remains poorly understood, despite their critical involvement in gestational diabetes mellitus (GDM), fetal macrosomia (FM) and offspring metabolic programming. This study included 62 mother–newborn dyads stratified by GDM and FM status. An analysis of the association of amino acids with clinical parameters was performed using the Spearman test. Amino acid markers of GDM were identified using the mutual information index and the Mann–Whitney test. A random forest method was used to identify amino acid markers, with the SHAP value used to estimate the contribution of each amino acid. In maternal serum, GDM was associated with significantly lower levels of glycine, 1-methylhistidine, γ-aminobutyric acid, lysine, and tryptophan. Umbilical cord serum from GDM pregnancies showed reduced concentrations of glutamine, glycine, asparagine, methionine, and proline. In amniotic fluid, GDM with FM was characterized by elevated lysine and 1-methylhistidine. Cord blood exhibited increased lysine, proline, leucine, and allo-isoleucine, while amniotic fluid showed low homocitrulline, asparagine, and lysine, together with high histidine. Fetal weight correlated directory with lysine and isoleucine and inversely with homocitrulline. Pathway analysis linked maternal serum markers to disturbances in biotin, glutamate, and carnitine metabolism, whereas cord blood markers involved broader alterations in amino acid, purine, and amino sugar metabolism. In amniotic fluid from GDM with FM, the methylhistidine pathway was specifically enriched, suggesting changes in neonatal muscle protein turnover. GDM induces distinct alterations in the amino acid profiles of all three compartments, and the combination with FM yields unique metabolic signatures. These findings identify candidate biomarkers for prediction of GDM and its complications and point to potential targets for metabolic intervention. Full article

Background/Objectives: Wolfram syndrome type 1 (WS1) is a rare, progressive, multisystem neurodegenerative disorder characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. As survival has improved, an increasing number of affected women are reaching reproductive age. However, evidence on pregnancy and peripartum management in WS1 remains scarce, and practical guidance is limited. This case report describes the multidisciplinary management of pregnancy and delivery in a woman with genetically confirmed WS1 and highlights key considerations for peripartum care. Case Presentation: A woman with genetically confirmed WS1 and long-standing multisystem involvement, including diabetes mellitus, diabetes insipidus, neurogenic bladder requiring frequent self-catheterization, progressive neurologic manifestations, and severe sensory impairment, achieved pregnancy through assisted reproduction with oocyte donation and was closely monitored by a multidisciplinary team. Due to persistent breech presentation, a planned external cephalic version was performed at 37 + 5 weeks’ gestation with immediate availability for cesarean delivery. After unsuccessful attempts, cesarean delivery was performed under combined spinal–epidural anesthesia. Peripartum management focused on strict glycemic control, careful monitoring of fluid balance and urine output, neuraxial anesthesia with proactive hemodynamic management, precautions related to the cochlear implant, and tailored communication strategies. Postpartum recovery was favorable, although anemia on postoperative day 1 required transfusion of one unit of packed red blood cells and intravenous iron therapy. Discussion and Conclusions: Pregnancy in WS1 represents a high-risk clinical scenario because of the coexistence of endocrine, urologic, and neurologic comorbidities, while published evidence on peripartum management remains limited. This case supports an individualized, multidisciplinary approach to obstetric and anesthetic planning and the use of a practical framework to optimize peripartum management and enhance maternal–fetal safety in this rare condition. Full article

Background/Objectives: We aimed to evaluate the association between diabetes mellitus (DM) during pregnancy and retinopathy of prematurity (ROP) in preterm infants younger than 32 gestational weeks or infants with low birthweight (<1500 g). Methods: We conducted a retrospective nested case–control study of all premature infants who were born alive and survived the post-delivery hospitalization period in Soroka Medical Center, with either gestational age younger than 32 weeks or birthweight less than 1500 g, during the years 2013–2021. The infants were divided into two groups according to ROP status. Multivariable Generalized Estimating Equations (GEE) were used to analyze the association between ROP and DM, adjusting for potential confounders, including maternal age, diabetes type (GDM vs. pre-gestational DM), gestational age, birthweight (<1250 g), duration of oxygen supplementation, antenatal corticosteroid courses, and birth plurality. Results: During the study period, there were 881 pairs of women and newborns who met the inclusion criteria. The ROP group included 345 infants (39.1%). Twenty-two (6.4%) of the mothers in the ROP group were diagnosed with DM during pregnancy compared with 52 of 536 (9.7%) in the control group (p = 0.082). ROP was associated with oxygen treatment (OR 1.05; 95% CI, 1.03–1.08; p < 0.001), birthweight < 1250 g (OR 2.70; 95% CI, 1.93–3.78; p < 0.001) and advanced maternal age (OR 1.04; 95% CI, 1.01–1.06; p = 0.006). Prenatal steroid treatment was identified as a significant protective factor against ROP (OR 0.73; 95% CI, 0.60–0.89; p = 0.002). No statistically significant association was observed between maternal DM and ROP (OR 0.62; 95% CI 0.34–1.13; p = 0.12). These findings should be interpreted cautiously given the retrospective design and the limited availability of glycemic control data. Conclusions: Maternal diabetes mellitus was not significantly associated with the risk of ROP in this cohort. Full article