Cellular and Molecular Pathophysiology of Gestational Diabetes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11641 - 11641

Published: Oct. 30, 2024

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence approximately 14%, with risk factors including obesity, family history of diabetes, advanced age, ethnicity, which are linked to cellular molecular disruptions in regulation insulin resistance. GD associated short- long-term complications for both the mother newborn. For mothers, increases developing type 2 cardiovascular diseases, syndrome. In offspring, exposure utero predisposes them intolerance, disorders later life. This review aims elucidate complex mechanisms underlying inform development effective therapeutic strategies. A systematic was conducted using medical subject headings (MeSH) terms related GD's pathophysiology. Inclusion criteria encompassed original studies, reviews, meta-analyses focusing on impact health, adhering PRISMA guidelines. Data extraction captured study characteristics, outcomes, key findings, conclusions. disrupts signaling pathways, leading impaired uptake Mitochondrial dysfunction reduces ATP production reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, dysregulation mammalian target rapamycin (mTOR) pathway further impair signaling. Gut microbiota alterations, gene expression, epigenetic modifications play significant roles GD. Ferroptosis placental primarily contribute intrauterine growth restriction. Conversely, macrosomia arises from hyperglycemia subsequent hyperinsulinemia, resulting excessive growth. The inflammatory state stress exacerbate these complications, creating hostile environment. pathophysiology involves multiple signaling, mitochondrial function, Effective management requires early detection, preventive strategies, international collaboration standardize care improve outcomes mothers babies.

Language: Английский

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Air Pollution Exposure and Gestational Diabetes Mellitus Risk: A Retrospective Case–Control Study with Multi-Pollutant Analysis in Wuhan, Hubei Province

Toxics, Journal Year: 2025, Volume and Issue: 13(2), P. 141 - 141

Published: Feb. 19, 2025

Ambient air pollution has been associated with gestational diabetes mellitus (GDM); however, evidence regarding trimester-specific effects from China remains limited. This case-control study analyzed data pregnant women who delivered in Wuhan, China, between 2017 and 2022 (164 GDM cases 731 controls), integrating geographic information, quality measurements, maternal characteristics. Using Inverse Distance Weighting interpolation Generalized Linear Mixed Models (GLMM), we assessed associations pollutant exposure across different periods. Results indicated that NO2 demonstrated the strongest association compared to other pollutants. Specifically, increased was consistently higher risk throughout pregnancy. PM2.5 showed significant during early mid-pregnancy, while SO2 significantly exclusively Sensitivity analyses stratified by urban maternity status age revealed stability of study's findings. These findings underscore importance reducing pregnancy implementing targeted interventions for high-risk populations prevent development.

Language: Английский

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Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2320 - 2320

Published: March 5, 2025

Gestational diabetes mellitus (GDM) is characterized by an inadequate pancreatic β-cell response to pregnancy-induced insulin resistance, resulting in hyperglycemia. The pathophysiology involves reduced incretin hormone secretion and signaling, specifically decreased glucagon-like peptide-1 (GLP-1) glucose-dependent insulinotropic polypeptide (GIP), impairing effects. Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) interleukin-6 (IL-6), impair receptor substrate-1 (IRS-1) phosphorylation, disrupting insulin-mediated glucose uptake. dysfunction GDM associated with duodenal homeobox 1 (PDX1) expression, increased endoplasmic reticulum stress markers (CHOP, GRP78), mitochondrial leading impaired ATP production glucose-stimulated secretion. Excessive gestational weight gain exacerbates resistance through hyperleptinemia, which downregulates expression via JAK/STAT signaling. Additionally, hypoadiponectinemia decreases AMP-activated protein kinase (AMPK) activation skeletal muscle, GLUT4 translocation. Placental hormones such as human placental lactogen (hPL) induce lipolysis, increasing circulating free fatty acids activate C, inhibiting 11β-hydroxysteroid dehydrogenase type (11β-HSD1) overactivity elevates cortisol levels, glucocorticoid receptors further reduce sensitivity. diagnostic thresholds (≥92 mg/dL fasting, ≥153 post-load) are lower than 2 prevent fetal hyperinsulinemia macrosomia. Management strategies focus on lifestyle modifications, dietary carbohydrate restriction exercise. Pharmacological interventions, or metformin, aim restore AMPK signaling hepatic output. Emerging therapies, (GLP-1R) agonists, show potential improving glycemic control reducing inflammation. A mechanistic understanding of essential for developing targeted therapeutic both adverse pregnancy outcomes the progression overt affected women.

Language: Английский

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Impact of Gestational Diabetes Mellitus on Fetal Growth and Nutritional Status in Newborns

Nutrients, Journal Year: 2024, Volume and Issue: 16(23), P. 4093 - 4093

Published: Nov. 27, 2024

Background: Gestational diabetes mellitus (GDM) is one of the most prevalent complications associated with pregnancy, exhibiting a gradual rise in prevalence worldwide. Given potential for numerous short- and long-term both mother child, patients diagnosed GDM require individualised treatment to compensate metabolic abnormalities ultimately reduce risk known adverse consequences impaired glucose tolerance. Methods results: The manuscript presents summary current knowledge on changes maternal metabolism during physiological pregnancy complicated by gestational diabetes. Furthermore, article provides synthesis findings from recent research examining impacts therapeutic modalities employed nutritional status fetus neonate. Additionally, review elucidates function placenta placental hormones fetal development, as well impact hyperglycemia, insulin resistance adipokines neonatal programming predisposition adulthood. Conclusions: environment, resulting abnormal tolerance exerts particularly significant growth and, consequently, birth weight fat mass newborn infants. This pivotal factor influencing developing fetus, predisposing individual development throughout their lifetime.

Language: Английский

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Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 23, 2024

Fetal and neonatal development is a critical period for the establishment of future metabolic health disease risk an individual. Both maternal undernutrition overnutrition can result in abnormal fetal organ resulting inappropriate birth size, child adult obesity, increased Type 2 diabetes cardiovascular diseases. Inappropriate adaptive changes to pancreas, placental function, pancreas response nutritional stress during pregnancy are major contributors trajectory offspring. This interconnected maternal-placental-fetal axis driven by endocrine signals availability metabolites cellular premature aging tissues expression key genes involved control as long-lasting epigenetic changes. Such insufficient pancreatic beta-cell mass reduced insulin sensitivity target such liver white adipose altered hypothalamic satiety centres basal glucocorticoid levels. Whilst interventions obese mother dieting exercise, or treatment with metformin mothers who develop gestational diabetes, improve reduce large-for-gestational age infant, their effectiveness changing adverse yet unclear.

Language: Английский

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Genetic and epigenetic alterations associated with gestational diabetes mellitus and adverse neonatal outcomes

World Journal of Clinical Pediatrics, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 20, 2024

Gestational diabetes mellitus (GDM) is a metabolic disorder, recognised during 24-28 weeks of pregnancy. GDM linked with adverse newborn outcomes such as macrosomia, premature delivery, cardiovascular, and neurological disorders. Recent investigations have focused on the correlation genetic factors β-cell function insulin secretary genes (transcription factor 7 like 2, potassium voltage-gated channel subfamily q member 1, adiponectin etc. ) maternal metabolism gestation leading to GDM. Epigenetic alterations DNA methylation, histone modification, miRNA expression can influence gene play dominant role in feto-maternal pathways. Interactions between environment, resulting differential patterns may lead Researchers suggested that women are more susceptible resistance, which alters intrauterine surroundings, hyperglycemia hyperinsulinemia. modifications affecting neuroendocrine activities, metabolism, increase risk obesity type 2 offspring. There currently no treatment or effective preventive method for GDM, since molecular processes resistance not well understood. The present review was undertaken understand pathophysiology its effects neonatal outcomes. In addition, study epigenetic will provide researchers search predictive biomarkers.

Language: Английский

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Dictamnine Reduces Gestational Diabetic Complications in Streptozotocin-Induced Diabetic Pregnant Rats via Regulating Inflammation and NOX-2, MCP-1/AGE–RAGE Pathway

Revista Brasileira de Farmacognosia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Abstract Gestational diabetes mellitus is a type of that arises during pregnancy. Around 15–25% pregnancies are affected by gestational mellitus, which involves hyperglycemia, insulin resistance, and abnormal fetal development. The present work was conducted to reveal the therapeutic potentials dictamnine against streptozotocin-induced in rats. To induce pregnant rats were administered streptozotocin, subsequently, given for 14 days. Following end treatments, body weight, blood glucose, fetus placental weights measured. concentrations biochemical markers, including fasting insulin, HbA1c, hepatic glycogen, analyzed. lipid profiles, antioxidant levels, apoptotic proteins, inflammatory cytokine levels measured using test kits. A histopathological investigation on pancreatic tissues obtained from experimental Dictamnine treatment at 15 30 mg/kg successfully reduced glucose increased regulated other marker with mellitus. resulted an increase lowered markers also cytokines, molecular histological study likewise confirmed capabilities dictamnine. results current emphasize has positive effect reducing Graphical

Language: Английский

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Role of miR-125b-5p in Modulating Placental SIRT7 Expression and Its Implications for Lipid Metabolism in Gestational Diabetes

Journal of Reproductive Immunology, Journal Year: 2024, Volume and Issue: 167, P. 104422 - 104422

Published: Dec. 25, 2024

Language: Английский

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