Search Results (1,193)

Gestational diabetes mellitus (GDM) is an increasingly prevalent metabolic disorder of pregnancy, driven by rising maternal age, obesity, and complex metabolic–inflammatory interactions. Emerging evidence implicates the maternal microbiome as a key modulator of metabolic adaptation during gestation; however, its precise role in GDM pathogenesis remains incompletely defined. This narrative review synthesizes current knowledge on microbiome alterations across gut, vaginal, and oral niches, focusing on their contribution to insulin resistance, metabolic endotoxemia, and immune dysregulation. GDM is consistently associated with reduced microbial diversity, depletion of beneficial taxa (e.g., Akkermansia, Bifidobacterium, Faecalibacterium), and expansion of pro-inflammatory pathobionts, which collectively may impair intestinal barrier integrity and promote low-grade systemic inflammation. These mechanisms are linked to altered insulin signaling and adverse maternal–fetal outcomes. In parallel, microbiome-derived metabolites and early taxonomic signatures have been proposed as potential biomarkers for first-trimester risk stratification, offering an opportunity to overcome the limitations of late diagnostic approaches such as the oral glucose tolerance test. Despite these advances, most available evidence remains associative, with substantial heterogeneity across studies and limited mechanistic validation. The clinical utility of microbiome-based interventions—including dietary modulation, prebiotics, and probiotics—remains promising but inconclusive, with outcomes highly dependent on individual, microbial, and methodological factors. Overall, the maternal microbiome represents a compelling but still evolving target in GDM research. Future progress will depend on standardized methodologies, longitudinal multi-omics studies, and the development of precision medicine approaches capable of integrating microbial, metabolic, and host data. Such advances may enable earlier diagnosis, targeted prevention, and ultimately the disruption of intergenerational metabolic risk. Full article

Background: Gestational diabetes mellitus (GDM) affects between 1% and 14% of pregnancies worldwide. Major risk factors include advanced maternal age, excess adiposity, family history of type 2 diabetes, and unhealthy dietary habits. In Mexico, evidence on the association between dietary patterns and GDM remains scarce, particularly in socioeconomically vulnerable populations with limited access to specialized nutrition services. This study aimed to evaluate the association between dietary patterns and the presence of GDM in pregnant women attending the outpatient obstetrics clinic of a teaching public hospital in Guadalajara, México. Methods: We conducted a case–control study including 169 pregnant women: 71 with GDM confirmed by the ADA one-step 75 g oral glucose tolerance test OGTT criteria and 98 without GDM based on a negative OGTT, recruited consecutively from the same clinic during the same period. Dietary intake was assessed using a culturally adapted and validated Food Frequency Questionnaire. Dietary patterns were identified through Principal Component Analysis, and associations were examined using logistic regression adjusted for maternal age, pregestational BMI, and family history of type 2 diabetes. Results: Women with GDM had higher maternal age, greater pregestational BMI, and more frequent family history of type 2 diabetes compared with controls. Three dietary patterns were identified: Western, Healthy, and Dairy/Refined. High adherence to the Western pattern was inversely associated with GDM (aOR = 0.36; 95% CI: 0.16–0.78; p = 0.010); however, this finding most likely reflects post-diagnosis dietary modifications rather than a protective effect, while maternal age remained the strongest risk factor (OR = 1.09; 95% CI: 1.03–1.16; p = 0.002). The Healthy pattern (aOR = 1.25; 95% CI: 0.55–2.82; p = 0.593) and the Dairy/Refined pattern (aOR = 0.80; 95% CI: 0.39–1.66; p = 0.554) were not significantly associated with GDM in the adjusted model. Conclusions: GDM was associated with older maternal age, higher pregestational BMI, and family history of T2DM. The inverse association with the Western pattern may reflect post-diagnosis dietary changes rather than a protective effect. Due to the retrospective design, causal inference is not possible, highlighting the need for longitudinal studies. Full article

Gestational Diabetes Mellitus (GDM) represents a significant public health concern due to its association with adverse maternal and neonatal outcomes, as well as elevated long-term metabolic risks. Its prevalence varies substantially depending on the diagnostic criteria used and the population studied. Women with GDM frequently experience heightened stress, anxiety, and uncertainty, underscoring the need for accessible information, counseling, and ongoing support to navigate glucose monitoring, dietary adjustments, and treatment regimens. Although clinical management has been extensively studied, research has largely focused on metabolic monitoring and therapeutic interventions, often underemphasizing prevention strategies, women’s informational needs, and maternal psychological well-being. Emerging evidence and international guidelines increasingly advocate for integrating these components into structured, woman-centered GDM care plans that actively involve families. Such approaches empower women to engage in self-management, enhance health literacy, support adherence to lifestyle and pharmacological interventions, and promote sustainable behavioral changes. This narrative review presents a comprehensive, holistic model of care across the perinatal continuum, emphasizing early risk identification, preventive strategies, and multidisciplinary coordination. Core elements include individualized antenatal education, empathetic communication, and family engagement, fostering self-efficacy, continuity of care, and integration of medical, educational, and psychosocial interventions. Equipping healthcare professionals with the competencies to deliver this holistic, woman-centered framework is essential to optimize maternal and neonatal outcomes and mitigate the long-term health consequences of GDM. Full article

During pregnancy, hormonal, metabolic, and immunological changes influence the composition and function of maternal microbial communities. Increasing evidence suggests that the maternal microbiota—particularly in the vaginal, gut, and oral environments—plays a significant role in maintaining pregnancy homeostasis and supporting fetal development. In healthy pregnancies, the vaginal microbiota is typically dominated by Lactobacillus species, which help maintain a low vaginal pH and protect against ascending infections. However, disruption of this balance (vaginal dysbiosis) has been associated with obstetrical complications such as intrauterine infection and preterm birth. Similarly, the maternal gut microbiota undergoes trimester-specific changes that contribute to metabolic adaptations required for fetal growth, while alterations in microbial composition have been linked to metabolic disorders including gestational diabetes mellitus and preeclampsia. Changes in oral microbiota and periodontal disease have also been associated with adverse pregnancy outcomes through systemic inflammatory pathways and potential microbial translocation to the placenta. Recent advances in sequencing technologies have improved the understanding of host–microbiome interactions in pregnancy, although the existence of a placental microbiome remains controversial. Overall, maternal microbiota plays an important role in pregnancy physiology, and its dysregulation may contribute to obstetrical complications. Understanding these mechanisms may facilitate the development of microbiome-based diagnostic and therapeutic strategies in maternal–fetal medicine. Full article

Background: Assisted reproductive technology (ART) is increasingly utilized worldwide, and approximately 30% of ART pregnancies result in twin gestations. Chorionicity strongly influences perinatal risk, yet its specific impact on ART-conceived twins has not been systematically clarified. Objective: To compare obstetrical and neonatal outcomes in assisted ART-conceived monochorionic (MC) versus dichorionic (DC) twin pregnancies and evaluate the impact of chorionicity on maternal and perinatal outcomes. Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD42024600292). PubMed, Scopus, and Web of Science were searched through October 2024 for studies comparing obstetrical and neonatal outcomes in ART-conceived monochorionic and dichorionic twin pregnancies. Eligible studies were qualitatively synthesized. Results: Thirty-five studies comprising 15,648 ART-conceived twin pregnancies were included, including 371 monochorionic and 15,277 dichorionic pregnancies. MC pregnancies consistently demonstrated less favorable perinatal outcomes compared with DC pregnancies, including an earlier gestational age at delivery, increased prematurity, lower birth weight, and higher rates of perinatal mortality. By contrast, maternal complications, such as hypertensive disorders, gestational diabetes mellitus, PROM, and cesarean delivery, varied considerably across the studies without a consistent association with chorionicity. The baseline maternal characteristics were generally comparable between the groups. Conclusions: Monochorionicity in ART-conceived twin pregnancies is associated with increased adverse neonatal and perinatal outcomes, particularly prematurity and perinatal mortality, while maternal outcomes appear less clearly influenced by chorionicity. Standardized prospective studies are needed to further clarify the chorionicity-specific risks in ART twin pregnancies. Full article

Gestational diabetes mellitus (GDM), as one of the most common metabolic disorders occurring during pregnancy, represents a significant public health concern due to its rising prevalence and the numerous complications that can affect both the mother and the foetus. In recent years, there has been growing interest in the use of omics technologies, such as metabolomics and proteomics, in research on the pathogenesis and early detection of GDM. The aim of this paper was to summarise the current knowledge on metabolomic and proteomic changes observed in women with GDM and to assess the potential usefulness of these methods in identifying biomarkers of the disease. The narrative review was conducted in accordance with the PRISMA 2020 statement, using PubMed and Web of Science until 23 December 2025. The studies analysed show that GDM is associated with abnormalities in the metabolism of lipids, amino acids, carbohydrates and metabolites associated with the gut microbiota. The most commonly observed changes included: elevated levels of branched-chain amino acids, free fatty acids and purine metabolites, as well as changes in the metabolism of phospholipids and acylcarnitines. Multi-omics studies also indicate significant changes in plasma protein and lipid profiles. The data collected suggest that omics technologies may be a promising tool for identifying early biomarkers of GDM and for developing our understanding of the pathophysiological mechanisms of this condition. Nevertheless, further studies involving larger and more diverse patient populations are needed to confirm their diagnostic and clinical value. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) represents one of the most common pregnancy-related disorders and it is correlated to increased risks of adverse maternal and neonatal outcomes. The prognostic role of initial glycemic values in predicting neonatal hypoglycemia and other complications remains underexplored. Methods: This retrospective study analyzed 233 women diagnosed with GDM between 2018 and 2024. Participants were stratified into three risk groups based on diagnostic oral glucose tolerance test (OGTT) values: low-risk group (fasting plasma glucose [FPG] 92–100 mg/dL, 1 h < 180 mg/dL, 2 h < 153 mg/dL), intermediate-risk group (FPG 101–110 mg/dL or 1 h 180–190 mg/dL or 2 h 153–163 mg/dL), and high-risk group (FPG > 110 mg/dL or 1 h > 190 mg/dL or 2 h > 163 mg/dL). Neonatal hypoglycemia was defined as the primary outcome, whereas secondary outcomes comprised insulin requirements, continuous glucose monitoring (CGM) use, macrosomia, polyhydramnios, and perinatal complications. Results: Non-significant differences across groups were observed except for Caucasian predominance in the high-risk group. Hypoglycemia trended higher in intermediate- and high-risk groups (26% and 21% vs. 17%), as well as polyhydramnios (14.3% and 13.8% vs. 4.5%) without statistical significance. Overall metabolic control was excellent, with almost 70% of patients maintaining HbA1c values ≤ 5.5% throughout the pregnancy with early and limited use of insulin therapy (17.3%). Conclusions: Diagnostic OGTT stratification provides limited prognostic value in optimized GDM care with early CGM and insulin use. Although trends for hypoglycemia and polyhydramnios suggest potential utility, the excellent metabolic control likely flattened the differences between groups. Prospective trials with CGM metrics are needed to develop more refined risk models, potentially enabling a more personalized management. Full article

Introduction: Pregnancy in women with end-stage kidney disease (ESKD) remains rare and high-risk, despite advancements in dialysis and supportive care. Using a nationwide database in South Korea, this study examined the maternal and neonatal outcomes among women undergoing maintenance hemodialysis, with a particular focus on dialysis modality and treatment patterns. Methods: This population-based retrospective cohort study utilized data from the Korean National Health Insurance Service database. The study included all live births between 1 January 2014 and 31 December 2022, linked to mothers who underwent hemodialysis at least twice per week during pregnancy. Results: Between 2014 and 2022, in the Republic of Korea, 31 live births were recorded among 29 women undergoing hemodialysis. The mean maternal age at delivery was 36.1 ± 4.94 years, and most patients had significant comorbidities, including hypertension (79.3%), and diabetes mellitus (48.3%). Cesarean section was the predominant mode of delivery (75.9%). Pregnancy-related complications included preterm delivery (48.4%), preeclampsia (16.1%), and gestational diabetes (16.1%). A total of 16.1% of the neonates had atrial septal defects. During the peripartum period, 93.1% of deliveries occurred at tertiary care centers, and trimester-wise escalation in dialysis frequency was observed. Conclusions: This study provided real-world data on pregnancy-related outcomes among women with ESKD undergoing maintenance dialysis in Korea. Given the rarity of this clinical condition, our findings may serve as a valuable reference for the management of pregnant women with ESKD. Full article

Purpose: To review the long-term cardiovascular risks associated with three common perinatal endocrine disorders—gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and thyroid dysfunction (including postpartum thyroiditis)—and to identify opportunities for early risk stratification and prevention. Materials and Methods: We conducted a structured literature search of PubMed and Web of Science for peer-reviewed articles published between January 2000 and December 2025. Search terms included combinations related to GDM, HDP, thyroid dysfunction, and cardiovascular disease (CVD). We prioritized prospective cohort studies, meta-analyses, systematic reviews, and major clinical guidelines. Key findings were synthesized thematically. Results: GDM is associated with a 1.6- to 2-fold increased risk of future CVD, HDP with a 1.8-fold increase, and subclinical hypothyroidism with a two-fold increase. These risks persist for decades, are independent of traditional risk factors, and are amplified by obesity, recurrence, and social determinants of health. Converging pathophysiological mechanisms include persistent insulin resistance, chronic low-grade inflammation, endothelial dysfunction, autonomic dysregulation, epigenetic modifications, and subclinical myocardial remodeling. The placenta serves as a central endocrine–cardiovascular interface, releasing anti-angiogenic factors, pro-inflammatory cytokines, and exosomal microRNAs. Despite this evidence, postpartum screening uptake remains below 50%, care is fragmented, and pregnancy history is not incorporated into CVD risk calculators. Conclusion: A life-course approach integrating structured postpartum screening (6–12 weeks and annually), lifestyle interventions, targeted pharmacotherapy, and multidisciplinary cardio-obstetrics programs is urgently needed to reduce the global burden of premature heart disease, stroke, and heart failure in women. Full article

Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder characterized by insulin resistance and systemic inflammation. Emerging evidence suggests that the Wnt/β-catenin signaling pathway may play a role in metabolic dysregulation; however, its clinical relevance in GDM remains unclear. This study aimed to evaluate the diagnostic value of Wnt signaling-related biomarkers, including Wnt-inhibitory factor 1 (WIF-1), secreted frizzled-related protein-4 (SFRP-4), and beta-catenin-1 (CTNNB1) in GDM. Methods: This case–control study included 60 patients with GDM and 60 healthy pregnant controls. Serum levels of WIF-1, SFRP-4, and CTNNB1 were measured and compared between groups. Receiver operating characteristic (ROC) and multivariable logistic regression assessed diagnostic performance and predictors, while correlation analysis and principal component analysis (PCA) evaluated biomarker relationships. Results: Serum levels of WIF-1, SFRP4, and CTNNB1 were significantly higher in the GDM group (all p < 0.001). ROC analysis showed moderate diagnostic performance for individual biomarkers, with CTNNB1 demonstrating the highest discriminative ability. The combined biomarker model significantly improved diagnostic accuracy, yielding the highest area under the curve (AUC), sensitivity, and specificity. In multivariable analysis, all three biomarkers remained independently associated with GDM. Correlation analysis revealed moderate interrelationships, with SFRP4 acting as a central component. PCA demonstrated partial separation between GDM and control groups, supporting the ability of Wnt signaling-related biomarkers to capture disease-associated biological variation. Conclusions: Wnt signaling-related biomarkers, including WIF-1, SFRP4, and CTNNB1, are significantly elevated in GDM and show promising diagnostic value. The combined biomarker approach provides superior discriminative performance compared to individual markers, highlighting its potential role in improving risk stratification and personalized management. Full article

Background: Gestational diabetes mellitus (GDM) adversely affects offspring neurobehavioral outcomes, yet evidence regarding continuous markers of maternal glucose metabolism remains limited. Although polyunsaturated fatty acids (PUFAs) have been shown to affect associations between glucose metabolism and respiratory outcomes, their effects on children’s emotional and behavioral problems remain unclear. This study investigated the association between maternal glucose metabolism and emotional and behavioral problems in children and the potential modifying effect of maternal erythrocyte PUFAs. Methods: This prospective birth cohort included 481 mother–child pairs. Maternal glucose metabolism during pregnancy was assessed using GDM diagnosis via a 75 g oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), 1 h and 2 h OGTT glucose, hemoglobin A1c (HbA1c), insulin, and insulin resistance (HOMA-IR). Maternal erythrocyte PUFAs were quantified by gas chromatography. Children’s emotional and behavioral problems at age 5 years were assessed using the Strengths and Difficulties Questionnaire (SDQ). Generalized linear models were used to evaluate associations, including multiplicative interaction terms between glucose metabolism indicators and PUFAs. Results: Maternal FPG (OR = 1.63; 95%CI: 1.08–2.47), OGTT-1h glucose (OR = 1.84; 95%CI: 1.08–3.12), and HOMA-IR (OR = 1.52; 95%CI: 1.01–2.27) were each positively associated with an increased risk of abnormal total difficulties scores in children. Maternal insulin levels were positively associated with abnormal total difficulties scores in girls (p for interaction < 0.05). Higher maternal n-3 PUFA levels and lower n-6 PUFA levels attenuated the risk of glucose metabolism-related emotional and behavioral problems in children. Conclusion: Maternal glucose metabolism was associated with increased risk of emotional and behavioral problems in children. PUFA biomarkers could modify glucose-related emotional and behavioral outcomes in children. Full article

Background/Objectives: Gestational Diabetes Mellitus (GDM) involves metabolic alterations that may affect breast milk composition. Imbalances in protein and fatty acid (FA) profiles have been reported in mature milk from mothers with GDM. However, evidence for colostrum and transitional milk is limited, despite the key role of ω-3 and ω-6 Polyunsaturated fatty acids (PUFAs) in neonatal neurodevelopment. This study compared ω-3 and ω-6 PUFAs and protein concentrations in colostrum and transitional milk from women with and without GDM. Methods: This cross-sectional study was conducted from January 2023 to December 2024. Women aged ≥ 18 years with GDM and non-GDM pregnancies recruited at Hospital General de México “Dr. Eduardo Liceaga” were included. Colostrum and transitional milk samples were collected at 0–5 and 6–14 days postpartum, respectively. To assess whether postpartum time (hours) and maternal group (non-GDM vs. GDM) affected milk volume, an analysis of covariance (ANCOVA) was performed. Differences in milk composition between the GDM and non-GDM groups were assessed using Student’s t test or the Mann–Whitney U test, according to variable distribution. Results: A total of 71 milk samples were analyzed: 51 colostrum samples (25 from women with GDM and 26 from women with non-GDM) and 20 transitional milk samples (10 from women with GDM and 10 from women with non-GDM). A moderate correlation was observed between milk volume and postpartum time, with no significant differences between the GDM and non-GDM groups. Colostrum from women with GDM had lower protein content compared with milk from women with non-GDM (3.8 ± 0.4 vs. 5.2 ± 0.5 g/dL, p = 0.02) and transitional milk (1.4 ± 0.2 vs. 2.2 ± 0.2 g/dL, p = 0.02). Transitional milk from GDM group showed higher total fat (5.7 ± 1.8 vs. 2.0 ± 0.4 g/100 g, p = 0.05) and fat-to-protein ratio (3.9 ± 1.1 vs. 1.0 ± 0.3, p = 0.02), along with an increased ω-6/ω-3 ratio driven by higher linoleic acid and lower α-linolenic acid concentrations. Conclusions: GDM was associated with variations in breast milk protein and FA profiles with a potential negative impact on the newborn’s neurodevelopment. Full article

Background/Objectives: Maternal hyperglycemia is associated with adverse neurodevelopmental outcomes in offspring; however, its long-term effects on brain aging remain unclear. This study investigated whether maternal hyperglycemia induces persistent molecular and behavioral alterations in aged male offspring and whether maternal palmitoleic acid supplementation exerts protective effects. Methods: The pregnant rats were divided into four groups: PCM, PDM, PDM/CPA, and PDM/TPA. Male offspring were analyzed at 48 weeks of age. Results: Maternal hyperglycemia significantly increased cerebral RAGE expression (~1.6-fold) and tau phosphorylation (~1.8-fold), accompanied by reduced Akt phosphorylation, impaired Nrf2-related antioxidant responses, and increased inflammatory gene expression. These molecular alterations are associated with impaired recognition memory, as reflected by a marked reduction in the discrimination index in the novel object recognition test. Maternal CPA/TPA supplementation partially attenuated these abnormalities. Conclusions: These findings suggest that maternal hyperglycemia may induce long-lasting molecular alterations associated with neuroinflammation, impaired insulin-related signaling, and cognitive dysfunction in aged offspring. Maternal palmitoleic acid supplementation may partially mitigate the adverse developmental alterations associated with intrauterine hyperglycemic exposure. Full article

Background: The prevalence of GDM is increasing and is associated with maternal health and neonatal complications. Therapeutic intervention for this condition is important for the health of both mothers and their unborn children. Objective: The present meta-analysis evaluates the effects of pharmacological, nutritional, and physical activity interventions on maternal and neonatal outcomes in women with GDM, including glucometabolic control, weight gain, blood pressure, lipid profiles, and pregnancy complications. Methods: Multiple databases were systematically searched for studies investigating GDM interventions and their effects on maternal and neonatal outcomes, including at least one of the following endpoints: 2 h postprandial glycemia, FBG, HbA1c, triglycerides, cholesterol, weight gain, blood pressure, cesarean delivery, preeclampsia, gestational age at delivery, neonatal hypoglycemia, neonatal complications, birth weight, preterm birth, Apgar score at 5 min, macrosomia, and NICU admission. Initial screening identified 204 records, which were narrowed to 17 studies meeting the eligibility criteria for inclusion in the meta-analysis following multi-author relevance review. Six reviewers independently extracted data and resolved discrepancies through consensus. Study quality was appraised by two reviewers using the Cochrane Risk of Bias tool, and data were analyzed using the RevMan Web software with random-effects models. Results: Pharmacological, nutritional, and physical activity interventions in women with gestational diabetes mellitus demonstrated statistically significant reductions in gestational weight gain and cesarean delivery rates. No statistically significant effects were observed for HbA1c, fasting blood glucose, 2 h postprandial glucose, lipid profiles, or blood pressure. Several outcomes, including preeclampsia, neonatal hypoglycemia, neonatal complications, and NICU admission, showed non-significant trends toward benefit, but these findings were based on limited data and should be interpreted cautiously. No meaningful effects were observed for gestational age at delivery, neonatal birth weight, preterm birth, Apgar score, or macrosomia. Substantial heterogeneity was present across metabolic outcomes, limiting the interpretability of pooled estimates. Conclusions: Nutritional and physical activity interventions significantly reduce HbA1c, gestational weight gain, and cesarean delivery in women with GDM, with protective trends for preeclampsia and neonatal complications. However, effects on lipid profiles and blood pressure remain inconsistent. Personalized, multimodal strategies integrating pharmacological, nutritional, and lifestyle modifications are necessary for optimal GDM management. Full article

Gestational diabetes mellitus (GDM) is increasingly recognized as a complex pathology rooted in systemic and organelle-level dysfunction, specifically involving chronic low-grade inflammation (CLGI), mitochondrial impairment, and endoplasmic reticulum (ER) stress. Central to this pathophysiology is mitochondrial dysfunction, characterized by reduced respiration, impaired metabolic flexibility, and dysregulated fission/fusion machinery, which fuels a self-perpetuating cycle of reactive oxygen species (ROS) production. Concurrently, chronic ER stress triggered by hyperglycemia and lipotoxicity activates the unfolded protein response (UPR), further amplifying redox imbalance through the Endoplasmic Reticulum Oxidoreductin 1/Protein Disulfide Isomerase (ERO1/PDI) axis and bridging metabolic toxicity to inflammation via c-Jun N-terminal kinase (JNK) and nuclear factor kappa-light-chain–enhancer of activated B cells (NF-κB) signaling. The Advanced Glycation Endproducts (AGEs) and the Receptor for Advanced Glycation Endproducts (RAGE) axis act as a molecular catalyst that sequester antioxidants and drive pro-inflammatory feedback loops. These converging mechanisms culminate in profound placental maladaptation, including structural abnormalities like chorangiosis and functional defects in nutrient transport mediated by hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. This review article provides insight into recent evidence to elucidate the meta-inflammatory environment of GDM, where modest but sustained elevations in biomarkers like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) disrupt redox homeostasis and impair insulin signaling pathways through the activation of stress-sensitive kinases. By integrating these molecular perspectives, the article underscores the necessity of targeting the systemic inflammatory and oxidative continuum spanning pre-conception to the antenatal period through lifestyle interventions and emerging therapeutic strategies to mitigate GDM risk and improve maternal–fetal outcomes. Full article