Search Results (140)

Background: Gestational diabetes mellitus (GDM) is an increasingly prevalent metabolic disorder of pregnancy. Beyond its well-established metabolic consequences, growing evidence suggests that exposure to maternal hyperglycemia during fetal life may influence immune system development and increase the risk of allergic diseases in offspring. Objective: This study aimed to systematically review the available evidence on the association between gestational diabetes mellitus and the development of allergic diseases in children, with particular emphasis on immunological mechanisms and the role of early-life gut microbiota. Methods: A systematic review was conducted using the PubMed and Scopus databases. Original human and animal studies, including cohort, case–control, cross-sectional, and clinical studies, were eligible for inclusion. Study selection followed PRISMA guidelines and was performed independently by three reviewers. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results: The included studies suggest that children born to mothers with GDM may have an increased risk of developing allergic diseases, particularly atopic dermatitis, food allergy, allergic rhinitis, and urticaria. Associations with childhood asthma were less consistent and appeared to depend on maternal body mass index, glycemic control, and duration of follow-up. Evidence suggests that maternal hyperglycemia may disrupt fetal immune programming through chronic low-grade inflammation, oxidative stress, altered cytokine profiles, and impaired regulatory T-cell development. Additionally, GDM has been associated with early alterations in neonatal gut microbiota composition and metabolic pathways, which may further contribute to immune dysregulation and increased susceptibility to allergic diseases. Importantly, effective metabolic control during pregnancy was associated with a lower risk of adverse allergic outcomes in offspring. Conclusions: GDM may represent an important prenatal exposure associated with altered immune maturation and a higher risk of allergic diseases in offspring. Early metabolic disturbances, immune dysregulation, and alterations in gut microbiota appear to be key mechanisms underlying this association. Optimizing glycemic control during pregnancy and implementing early-life preventive strategies may reduce the long-term burden of allergic diseases. Further well-designed longitudinal and mechanistic studies are required to clarify causal pathways and identify effective preventive interventions. 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

Objectives: Gestational diabetes is linked to increased inflammatory and metabolic stress during the neonatal period. Among the biomarkers elucidating the relationship between diabetes and inflammation, the interleukin-33 (IL-33)/ST2 signaling pathway is of particular interest. Research on the IL-33/sST2 axis in pregnancies complicated by diabetes indicates that these biomarkers are associated with maternal metabolic disorders and inflammation. Therefore, evaluating sST2 levels in infants of diabetic mothers is essential for identifying a biological marker of systemic inflammation resulting from intrauterine hyperglycemia and for clarifying the specific risks associated with this condition. The objective of this study was to examine sST2 levels in infants born to diabetic mothers and to assess their association with perinatal inflammation, metabolic stress, and clinical outcomes. Methods: This prospective observational study included term infants born at Pamukkale University Medical Faculty Hospital. The study group comprised term infants whose mothers had gestational diabetes, while the control group consisted of term infants born to healthy mothers without diabetes. sST2 levels were measured from serum samples obtained from cord blood at birth using the ELISA method. Factors influencing sST2 levels were analyzed using regression analyses. Results: sST2 levels were significantly higher in the diabetic group than in the control group (p < 0.001). The incidences of large for gestational age (LGA), small for gestational age (SGA), hypoglycemia, postnatal respiratory distress, and both the frequency and duration of neonatal intensive care unit admissions were also significantly elevated in the diabetic group. Multivariate analysis identified gestational diabetes as independent predictor. Conclusions: This study is among the first to demonstrate increased sST2 levels at birth in infants of diabetic mothers. The results indicate that intrauterine exposure to hyperglycemia due to gestational diabetes may be associated with heightened inflammation and metabolic stress in the neonatal period, and that sST2 may serve as a potential biomarker reflecting fetal exposure. Full article

Background: The worldwide incidence of hyperglycemia in pregnancy is rising with the increasing prevalence of diabetes globally. In Qatar, Gestational Diabetes (GDM) is highly prevalent, at 31.6% of all pregnancies. Diabetes in pregnancy is associated with adverse maternal and fetal complications. This quality improvement practice project aimed to review the care pathway for managing diabetes in pregnancy with reference to the National Diabetes Guideline. Method: A retrospective audit was conducted through a chart review of electronic medical records for women who delivered at a tertiary maternity unit in Qatar, between 1 July 2022 and 31 December 2022. The audited criteria and standards were based on the National Guideline for Diabetes in Pregnancy in Qatar. Results: There were 737 deliveries during the study period. Overall, diabetes complicated 36.1% of births, and GDM was diagnosed in 34.6%. Of the patients with GDM, 197 (77.3%) were on diet control, 49 (19.2%) were on Metformin, and 9 (3.5%) were on Insulin. Pré-pregnancy weight was documented only in 140 (52.7%) women with diabetes. Of all the women with GDM, 52.9% were referred to see a dietician. Only 9 out of 164(5%) women with a BMI greater than 30 kg/m² had an early Oral Glucose tolerance (OGTT). Orders for postpartum OGTT were found for 33.7% of the women with GDM. Conclusions: The audit identified some gaps in the care pathway for managing diabetes during pregnancy, particularly in documentation practices, nutritional therapy referrals, and postpartum diabetes screening. Addressing these gaps and overcoming the implementation challenges are crucial for enhancing care quality. Full article

Background: Gestational diabetes mellitus (GDM) and periodontitis (PD) are chronic inflammatory conditions that may share metabolic and immune pathways. Evidence suggests an association between them, although results across studies remain inconsistent. This systematic review and meta-analysis evaluated the relationship between GDM and PD and examined whether GDM influences key periodontal parameters. Methods: A systematic search of PubMed/MEDLINE, Scopus, Web of Science, and Embase was conducted up to August 2025 following PRISMA guidelines. Observational studies comparing periodontal status in pregnant women with and without GDM were included. Periodontal status was assessed using probing pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP). Study quality was evaluated with the Newcastle–Ottawa Scale, and random-effects models were applied to estimate pooled associations. Results: Fifteen studies involving about 3800 pregnant women met the criteria. A significant association was found between GDM and PD (Odds Ratio [OR] 2.10; 95% Confidence Interval [CI] 1.64–2.69). No significant association emerged between GDM and gingivitis. Women with GDM showed increased BOP and higher PPD, indicating greater periodontal inflammation, while CAL did not significantly differ between groups. Conclusions: The findings support a significant association between GDM and periodontitis, suggesting that gestational hyperglycemia may enhance periodontal inflammation and early tissue changes. Incorporating periodontal screening into prenatal care may benefit maternal oral and metabolic health. Further longitudinal and interventional studies are needed to clarify causality and to explore whether periodontal therapy may help reduce risks linked to GDM. Full article

Pregnancies complicated by diabetes, including pregestational and gestational diabetes mellitus, are associated with increased maternal and fetal morbidity. Early identification of at-risk pregnancies is crucial for timely intervention and improved outcomes. Emerging evidence highlights the interplay of genetic predisposition, epigenetic modifications, and non-invasive biomarkers in the early detection of diabetic pregnancies. Genetic factors influencing insulin signaling, glucose metabolism, and pancreatic β-cell function may contribute to susceptibility to gestational hyperglycemia. Concurrently, epigenetic alterations, such as DNA methylation and histone modifications in maternal and placental tissues, have been linked to dysregulated metabolic pathways and adverse pregnancy outcomes. Non-invasive biomarkers, including circulating cell-free DNA and microRNAs in maternal blood, show promise for early diagnosis by offering a safer and more practical alternative to invasive testing. Integrating genetic, epigenetic, and molecular marker data could enhance risk stratification and enable personalized monitoring and management strategies. This review synthesizes current knowledge on the molecular underpinnings of diabetic pregnancies, evaluates the potential of emerging biomarkers for early diagnosis, and discusses the challenges and future perspectives for translating these findings into clinical practice. Understanding these mechanisms may pave the way for precision medicine approaches, ultimately improving maternal and neonatal outcomes in pregnancies affected by diabetes. Full article

Background and Objectives: Gestational diabetes mellitus (GDM) is a complex pregnancy condition that carries substantial risks for adverse pregnancy outcomes. Following the implementation of universal diagnostic criteria in our clinical practice, this study was undertaken to assess their applicability and to determine whether locally conducted clinical studies are beneficial before adopting globally applicable criteria. By retrospectively analyzing parameters relevant to GDM from medical records, we aimed to determine the suitability of existing diagnostic criteria for our population, taking into account distinct socioeconomic, demographic, and genetic factors, and to assess the validity of alternative criteria. Materials and Methods: We used data from 2183 pregnant women who underwent 75 g-OGTT between 24 and 28 weeks of pregnancy. Results of the plasma glucose (PG) measurements were used to assign women into four diagnostic groups: diagnosed and treated by IADPSG criteria, diabetes mellitus in pregnancy identified according to WHO-2006 criteria, identified according to CDA-2013 criteria, and identified according to Tomic et al. criteria, based on a study on our population. Pregnancy outcomes were extracted from medical records. Results: The prevalence of GDM was 18.7% by IADPSG criteria, comparable to published data. Adverse pregnancy outcomes were consistently more frequent in GDM groups across all diagnostic systems (46.6–80% versus 33.9–35.9% in non-GDM). Maternal BMI ≥ 25 kg/m² was also associated with having large-for-gestational-age (LGA) neonates, contributing to the influence of hyperglycemia. Excessive gestational weight gain was a predictor of complications such as macrosomia and cesarean delivery. Conclusions: Before adopting universal GDM diagnostic criteria, population-specific studies are valuable to balance detection rates and clinical accuracy. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in both children and adults. Pediatric MASLD, however, is not simply an early form of adult disease, as it exhibits distinct developmental, histological, and metabolic features. Emerging evidence suggests that these characteristics arise from a complex, multi-hit continuum that begins in utero. Maternal obesity, gestational diabetes, and poor diet quality during pregnancy have been associated with greater hepatic steatosis in offspring, raising the possibility that intrauterine exposure to dyslipidemia, hyperglycemia, and elevated free fatty acid flux may contribute to early hepatic lipid deposition. After birth, feeding behaviors such as a prolonged breastfeeding appear protective, whereas formula feeding, especially high added-sugar formulations, may accelerate rapid weight gain and increase susceptibility to later steatosis. Early childhood diets high in added sugars, saturated fats, and ultra-processed foods may further promote hepatic lipogenesis and inflammation and interact with underlying genetic susceptibility. Given the heterogeneity of available human cohort studies and mechanistic model systems, this narrative review summarizes converging evidence from prenatal, postnatal, and early childhood nutritional exposures and their relationship to offspring hepatic lipid accumulation, emphasizing early-life windows for intervention to reduce the burden of pediatric MASLD. Full article

Background. Gestational diabetes mellitus (GDM) induces maternal hyperglycemia, which may alter fetal cardiac structure and function, increasing short- and long-term cardiovascular risks. Purpose. To systematically review the evidence on the fetal cardiac structural and functional effects of GDM, to explore the diagnostic role of novel imaging and biochemical biomarkers, and to summarize the long-term cardiovascular complications associated with GDM. Materials and Methods. A systematic search of PubMed, Scopus, and Cochrane Library was conducted according to the PRISMA guidelines. All studies comparing cardiac outcomes in GDM and non-GDM pregnancies were included. Data on myocardial hypertrophy, diastolic and systolic function, imaging modalities, and biomarkers were extracted and qualitatively synthesized. Results. A total of twelve eligible studies were identified. Fetal cardiac hypertrophy and diastolic and early systolic dysfunction are common among GDM pregnancies and can be detected by dual-gate Doppler and speckle-tracking echocardiography. Abnormalities are observed in indices such as the myocardial performance index, E/A, E/e′ ratios, and global longitudinal and circumferential strain in fetuses and may persist in the neonatal period. Alterations may be more pronounced for the right ventricle compared to the left. Septal hypertrophy is associated with elevated umbilical cord pro-brain natriuretic peptide. The risk of early-onset cardiovascular disease in the progeny of diabetic mothers is 29% higher, as evidenced by population-based cohort data. Conclusions. GDM is linked to fetal cardiac remodeling and an increased long-term cardiovascular risk. Early detection and customized interventions to reduce adverse outcomes may be achieved by integrating advanced echocardiographic techniques and biomarkers into prenatal surveillance. Full article

Background/Objectives: Intracerebral hemorrhage (ICH) is primarily a disease of older adults, commonly linked to chronic hypertension and cerebral amyloid angiopathy. In young adults, however, ICH is rare and often driven by distinct structural, hematologic, or vascular causes. Methods: Using the National Inpatient Sample (2016–2022), we identified hospitalizations with a primary diagnosis of ICH (ICD-10-CM: I61.x). Patients younger than 18 years were excluded. Patients were stratified into 18–39 vs. ≥40 years. Comorbidities were defined using validated ICD-10 codes (E08–E13 for diabetes mellitus, I10–I15 for hypertension), excluding transient hyperglycemia (R73.x). Weighted analyses using NIS discharge weights compared demographics, comorbidities, rare etiologies, and outcomes, including in-hospital mortality, length of stay (LOS), and total hospital charges. Survey-weighted multivariable logistic regression identified independent predictors of mortality. Results: Among 76,264 ICH hospitalizations, 4012 (5.3%) occurred in patients < 40 years. Compared with older adults, younger patients had lower prevalence of hypertension (47.8% vs. 84.1%) and diabetes (10.2% vs. 60.4%) but higher rates of substance use (27.7% vs. 15.6%). Rare etiologies were more frequent, including arteriovenous malformation/aneurysm (14.0% vs. 3.6%), Moyamoya disease (1.4% vs. 0.2%), sickle cell disease (1.1% vs. 0.1%), and pregnancy-related ICH (0.05%). In-hospital mortality was lower among young adults (15.7% vs. 21.7%, p < 0.001), though LOS was longer (12.1 vs. 8.7 days, p < 0.001), and mean hospital charges were higher ($228,000 vs. $125,000, p < 0.001). Conclusions: Young-adult ICH is uncommon but etiologically distinct, often associated with vascular malformations, hemoglobinopathies, and substance use. Despite lower mortality, these patients experience longer and more resource-intensive hospitalizations, underscoring a substantial clinical and economic burden. Full article

Background: Gestational diabetes screening often employs the 50 g oral glucose tolerance test (OGTT), which induces acute hyperglycemia. This study aimed to investigate the effects of this acute hyperglycemia on uteroplacental and fetoplacental circulations in women between the 24th and 28th weeks of pregnancy using Doppler ultrasonography (USG). Methods: This prospective, single-center study included 209 pregnant women with singleton pregnancies followed at Bursa City Hospital between January and April 2021. Doppler USG measurements were taken before and 60 min after administering the 50 g OGTT. Venous blood samples were collected to measure blood glucose levels pre-test and one hour post-test. Doppler indices, including the pulsatility index (PI), resistive index (RI), and systolic/diastolic ratio (S/D) for the uterine arteries, umbilical artery (UA), and middle cerebral artery (MCA), were recorded and converted to Z scores based on gestational age. Fetal biometric parameters, including abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD), were also measured. Results: The study found a significant decrease in the mean MCA-PI, MCA RI, MCA S/D, and cerebroplacental ratio (CPR) values, as well as their respective Z scores, in the post-test measurements compared to pre-test values (p < 0.001 for all). No significant differences were observed in the S/D, RI, PI values, or Z scores of the uterine arteries and UA between pre-test and post-test measurements. Conclusions: Acute hyperglycemia induced by the 50 g OGTT significantly affects fetal cerebral circulation, evidenced by decreased MCA-PI, MCA RI, MCA S/D, and CPR values, but does not significantly impact uteroplacental circulation. Further large-scale studies are necessary to explore the effects of varying maternal glucose levels and the chronic impacts of non-physiological glucose levels on placental circulation. Full article

Gestational Diabetes Mellitus (GDM) is a metabolic condition characterized by glucose intolerance, which manifests or is diagnosed for the first time during pregnancy. Hyperglycemia associated with GDM can induce a systemic and local inflammatory environment, directly affecting the maternal–fetal interface, particularly the placenta. The placenta, in turn, plays a central role in immune modulation and can alter cytokine and immune cell expression in response to metabolic stress. This study aimed to evaluate levels of inflammatory cytokines and the profiles of type 1 (M1) and type 2 (M2) macrophages in placentas from pregnant women with GDM. Forty placental samples were analyzed and divided into two groups: pregnant women with GDM (n = 20) and normoglycemic pregnant women (n = 20). The villous and extravillous portions were separated and analyzed for cytokine levels by flow cytometry and for macrophage immunophenotyping. The results showed a significant increase in IL-6, IL-8, IL-10, and IL-12P70 levels in the placentas of mothers with GDM, whereas IL-1β and TNF-α were reduced in the extravillous portion of this group. In addition, a higher percentage of CD14+ cells and M2 macrophages was observed, especially in the villous portion of the placentas of pregnant women with GDM. These findings suggest that gestational hyperglycemia modulates the placental immune response, altering cytokine levels and macrophage polarization patterns. GDM influences the placental immunological microenvironment, which can contribute to alterations in placental function and increased risks to fetal development. The data underscore the placenta’s role as an immunoregulatory organ and highlight the need for greater attention to inflammation associated with GDM in maternal and child health. Full article

Background/Objectives: Prenatal environmental exposure may influence disease risk later in life. Previous studies suggest that season or month of birth affects susceptibility to various conditions, including type 2 diabetes. We aimed to evaluate whether birth timing is associated with gestational diabetes mellitus (GDM). Methods: We conducted a retrospective cohort study of 8744 pregnant women screened for GDM between August 2011 and March 2020, according to Italian Ministry of Health guidelines. Only women born and raised in Calabria were included. Logistic regression and Cosinor analysis were performed. Results: Birth distribution peaked in January (30.7%) and was lowest in October (22.3%). Being born in January was associated with higher GDM [OR 1.287 (1.090–1.520), p = 0.003], whereas October and June births were protective [OR 0.800 (0.672–0.954), p = 0.013, and OR 0.818 (0.682–0.980), p = 0.030, respectively]. Birth in cold months increased GDM risk [OR 1.196 (1.080–1.325), p < 0.001], while birth in warm months was protective [OR 0.834 (0.758–1.917), p < 0.001]. Cosinor analysis of fasting glucose at OGTT confirmed significant seasonal periodicity (p = 0.0053). Conclusions: Season and month of birth are associated with GDM risk, cold-month births predisposing and warm-month births protecting. These findings suggest that early-life seasonal factors, potentially including maternal hyperglycemia during pregnancy, may influence future GDM risk. Full article

Background: The pathogenesis of developing gestational diabetes mellitus (GDM) integrated with pregnancy-specific urinary incontinence (PSUI) may be related to immunological and hormonal factors. Inflammatory cytokines influence the function and regulation of the urinary tract, and changes in melatonin concentration are a predisposing factor for smooth muscle dysfunction and cystometric changes. Objective: This study examines the influence of melatonin, MT1 and MT2 receptors, and inflammatory cytokines in the blood and urine of pregnant women with GDM and PSUI. Methods: Two hundred sixty-nine pregnant women were approached during the diagnostic investigation of GDM and answered a specifically structured questionnaire about the involuntary loss of urine. According to these criteria, mothers were divided into four groups: continent normoglycemic (NG-C), incontinent normoglycemic (NG-I), continent GDM (GDM-C), and incontinent GDM (GDM-UI). Blood and urine samples were collected to determine the levels of melatonin, melatonin sulfate, melatonin receptors (MT1 and MT2), and inflammatory cytokines. Results: Blood level of melatonin and IL-10 was lower, but MT1, MT2, IL-1β, IL-8, and TNF-α were higher in GDM-UI compared with the NG-C group. The melatonin sulfate level was lower in the urine of the GDM-UI group compared with the NG-C group. Conclusions: Maternal hyperglycemia associated with urinary incontinence generates an inflammatory environment characterized by reduced melatonin and IL-10 and increased IL-1β, IL-8, and TNF-α in the blood of mothers with GDM with UI. This environmental condition may be involved in the pathogenesis of these pathologies. Full article

Background/Objectives: The classification of patients with diabetes into phenotypes with distinct risks and therapeutic needs is crucial for individualized care. We recently introduced a clustering model for gestational diabetes mellitus (GDM). This study aims to further characterize the proposed clusters and to identify cluster-specific differences in glucometabolic parameters during early pregnancy in an independent cohort. The metabolic profiles and dietary habits of GDM clusters will be compared with those of a normal glucose-tolerant (NGT) control group. Methods: 1088 women (195 who developed GDM and 893 who remained NGT) underwent a broad risk evaluation at early pregnancy. GDM patients were further categorized into the three proposed GDM subtypes (CL1 to CL3). Results: Among GDM patients, 7.7% were classified as CL1, 35.9% as CL2, and 56.4% as CL3. CL1 showed higher age, pregestational BMI, and increased glucose concentrations both at fasting and during the diagnostic oral glucose tolerance test. CL2 was characterized by elevated BMI and fasting glucose, while CL3 showed higher glucose concentrations after the oral glucose load, with BMI levels comparable to NGT mothers. Women in the CL1 group exhibited impaired insulin sensitivity and β-cell function at early pregnancy and showed elevated lipid levels. Compared to NGT women, a positive family history of diabetes was more prevalent in CL1 and CL3, but not in CL2. Dietary patterns were similar across all groups. Conclusions: Our study showed distinct alterations in glucometabolic parameters already at early pregnancy among GDM subtypes. Patients in CL1 exhibited the most unfavorable risk constellation and could benefit from lifestyle changes and nutrition therapy in early pregnancy, despite showing similar dietary patterns as the NGT group. Full article