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16 pages, 786 KiB  
Review
The Role of Vitamin D Supplementation in Type 1, Type 2, and Gestational Diabetes: A Comprehensive Updated Narrative Review
by Asala Nasser, Dimitrios Papandreou, Sousana K. Papadopoulou and Leila Cheikh Ismail
Clin. Pract. 2025, 15(8), 148; https://doi.org/10.3390/clinpract15080148 (registering DOI) - 7 Aug 2025
Abstract
Vitamin D has emerged as a modulatory factor in the pathogenesis and management of diabetes mellitus due to its influence on pancreatic β-cell function, immune regulation, and inflammatory pathways. This narrative review critically examines mechanistic and clinical evidence linking vitamin D status with [...] Read more.
Vitamin D has emerged as a modulatory factor in the pathogenesis and management of diabetes mellitus due to its influence on pancreatic β-cell function, immune regulation, and inflammatory pathways. This narrative review critically examines mechanistic and clinical evidence linking vitamin D status with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). In T1DM, vitamin D’s immunomodulatory effects are thought to protect β-cells from autoimmune destruction; epidemiological studies associate vitamin D sufficiency with lower T1DM incidence and improved glycemic control, although causality remains under investigation. In T2DM, vitamin D deficiency is associated with worsened metabolic control and may contribute to disease development in at-risk individuals; however, it does not influence the initial onset of T2DM in patients who are already diagnosed. Intervention trials indicate that correcting the deficiency can modestly improve insulin sensitivity, β-cell function, and metabolic parameters. GDM has similarly been linked to hypovitaminosis D, with low maternal vitamin D levels associated with higher GDM risk and adverse perinatal outcomes; mechanistic insights suggest that adequate vitamin D supports glucose homeostasis in pregnancy, and emerging trials demonstrate improved insulin resistance with maternal vitamin D supplementation. Across these diabetes subtypes, maintaining sufficient vitamin D levels appears to confer metabolic benefits and may serve as an adjunct to current preventive and therapeutic strategies. However, definitive evidence from large-scale trials is required to establish optimal vitamin D supplementation protocols and confirm its efficacy in diabetes care. Full article
(This article belongs to the Special Issue The Effect of Dietary Compounds on Inflammation-Mediated Diseases)
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13 pages, 3032 KiB  
Article
Combined Bioinformatic and Experimental Approaches to Analyze miR-182-3p and miR-24-3p Expression and Their Target Genes in Gestational Diabetes Mellitus and Iron Deficiency Anemia During Pregnancy
by Badr Alzahrani, Bisma Rauff, Aqsa Ikram and Mariya Azam
Curr. Issues Mol. Biol. 2025, 47(8), 610; https://doi.org/10.3390/cimb47080610 - 2 Aug 2025
Viewed by 153
Abstract
Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles [...] Read more.
Gestational diabetes mellitus (GDM) and iron deficiency anemia (IDA) are the most common pregnancy-related conditions resulting in adverse maternal and fetal complications. MicroRNAs (miRNAs), particularly miR-182-3p and miR-24-3p, are promising biomarkers as they act as regulatory elements in various diseases; however, their roles in GDM and IDA are unclear. The present study aimed to analyze the expression and functional relevance of miR-182-3p and miR-24-3p in GDM and IDA. Experimental validation via RT-PCR revealed significant upregulation of both miRNAs in GDM and IDA samples. We identified common target genes and signaling pathways associated with these miRNAs, using a combination of data mining, bioinformatic tools (miRDB, TargetScan, miRTarBase, and miRWalk), and differentially expressed gene (DEGs) analysis using the GEO, OMIM, MalaCards, and GeneCards datasets. GO and KEGG pathway analyses revealed that the shared miRNA–mRNA in target genes were enriched in insulin signaling, apoptosis, and inflammatory pathways—key mechanisms implicated in GDM and IDA. Furthermore, hub genes such as IRS1, PIK3CA, CASP3, MAPK7, and PDGFRB were identified, supporting their central role in metabolic dysregulation during pregnancy. These findings demonstrate the potential of miR-182-3p and miR-24-3p as diagnostic biomarkers and therapeutic targets in managing GDM and IDA, offering new insights into the molecular interplay underlying pregnancy complications. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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15 pages, 319 KiB  
Systematic Review
Vitamin D Deficiency and Risk of Gestational Diabetes Mellitus in Western Countries: A Scoping Review
by Paola Correa, Hirukshi Bennett, Nancy Jemutai and Fahad Hanna
Nutrients 2025, 17(15), 2429; https://doi.org/10.3390/nu17152429 - 25 Jul 2025
Viewed by 371
Abstract
Background: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication globally. Maternal vitamin D deficiency has been linked to the risk of GDM. The aim of this study was to explore and synthesise current evidence on the association between vitamin D deficiency and [...] Read more.
Background: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication globally. Maternal vitamin D deficiency has been linked to the risk of GDM. The aim of this study was to explore and synthesise current evidence on the association between vitamin D deficiency and the development of gestational diabetes in Western countries. Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodological framework. Relevant studies were identified through a comprehensive search across seven databases: ProQuest Public Health, Google Scholar, PubMed, ScienceDirect, The Lancet, BMC Public Health, the International Journal of Women’s Health, and Scopus. Studies were included based on predefined inclusion and exclusion criteria relevant to the research question. The review followed the JBI protocol, and the PRISMA flowchart was used to guide and visualise the study selection process. Results: Nineteen studies were included in the final analysis, comprising research predominantly from Australia (5), the United States (5), and Canada (4). The findings indicate a notable association between vitamin D deficiency and GDM risk, moderated by factors such as maternal age, ethnicity, seasonal variation, and body mass index (BMI). Older maternal age and higher BMI were linked with lower vitamin D levels and a higher incidence of GDM. Ethnic groups with darker skin tones showed higher rates of vitamin D deficiency, increasing vulnerability to GDM. Seasonal patterns revealed lower vitamin D levels during winter months, correlating with greater GDM risk. These patterns underscore the need for targeted preventive strategies, including the potential role of vitamin D supplementation. Conclusions: This review supports an observed association between maternal vitamin D deficiency and increased GDM risk, influenced by demographic and environmental factors. While the evidence points to a potential preventative role for vitamin D, further high-quality research, including systematic reviews and meta-analyses, is essential to establish causality and inform clinical guidelines. The review identifies knowledge gaps and suggests directions for future research and clinical practice. Full article
(This article belongs to the Section Nutrition and Diabetes)
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11 pages, 857 KiB  
Article
Placental Expression of Sirtuins in Women with Gestational Diabetes
by Michał Czerewaty, Łukasz Ustianowski, Kajetan Kiełbowski, Estera Bakinowska, Krzysztof Safranow, Maciej Tarnowski, Tomasz Sroczyński and Andrzej Pawlik
Genes 2025, 16(7), 844; https://doi.org/10.3390/genes16070844 - 20 Jul 2025
Viewed by 365
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnant women. It can lead to several complications, such as preterm delivery, macrosomia, or metabolic disorders in newborns. Studies have revealed morphological and transcriptional differences between the placentas of patients with GDM [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnant women. It can lead to several complications, such as preterm delivery, macrosomia, or metabolic disorders in newborns. Studies have revealed morphological and transcriptional differences between the placentas of patients with GDM and women with normal glucose tolerance. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent deacetylases that interact with and regulate the activity of numerous proteins. However, little is known about their role in the pathogenesis of GDM. This study was performed to analyze the placental expression of SIRTs and investigate their correlations with clinical parameters. Methods: GDM was diagnosed based on the 75 g oral glucose tolerance test in accordance with the criteria developed by the International Association of Diabetes and Pregnancy Study Groups. Placental tissues were collected, and the expression of SIRT1,-3,-4 and a reference gene (β-2 microglobulin) was analyzed. Results: The placental expression of SIRT1 and SIRT3 was elevated in women with GDM. However, there was no significant difference in SIRT4 expression between women with GDM and those with normal glucose tolerance. Furthermore, we found no significant correlations between SIRT1, SIRT3, and SIRT4 expression and clinical parameters. Conclusions: The findings of this study demonstrate elevated expression of SIRT1 and SIRT3 in the placentas of women with GDM. Further studies are required to confirm our observations and demonstrate the precise role of these enzymes in GDM. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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13 pages, 380 KiB  
Article
Association Between Carbohydrate Quality Index During Pregnancy and Risk for Large-for-Gestational-Age Neonates: Results from the BORN 2020 Study
by Antigoni Tranidou, Antonios Siargkas, Ioannis Tsakiridis, Emmanouela Magriplis, Aikaterini Apostolopoulou, Michail Chourdakis and Themistoklis Dagklis
Children 2025, 12(7), 955; https://doi.org/10.3390/children12070955 - 20 Jul 2025
Viewed by 283
Abstract
Background/Objectives: To assess the association between early pregnancy carbohydrate quality, as measured by the Carbohydrate Quality Index (CQI), and the risk of delivering a large-for-gestational-age (LGA) infant in a Mediterranean pregnant cohort of northern Greece. Methods: We analyzed singleton pregnancies from [...] Read more.
Background/Objectives: To assess the association between early pregnancy carbohydrate quality, as measured by the Carbohydrate Quality Index (CQI), and the risk of delivering a large-for-gestational-age (LGA) infant in a Mediterranean pregnant cohort of northern Greece. Methods: We analyzed singleton pregnancies from the BORN 2020 prospective cohort in Greece. Dietary intake was assessed via a validated food frequency questionnaire, and CQI was computed from glycemic index, fiber density, whole-to-refined grain ratio, and solid-to-liquid carbohydrate ratio. Multivariable logistic regression was used to estimate the association between CQI (in tertiles) and LGA risk, defined as birthweight >90th percentile. Results: Among the 797 participants, 152 (19.1%) delivered LGA infants, and 117 (14.7%) were diagnosed with GDM. Of those with GDM, 23 (19.7%) delivered LGA infants. In the total population, higher maternal weight (p < 0.001), height (p = 0.006), and pre-pregnancy BMI (p = 0.004) were significantly associated with LGA. A greater proportion of women with LGA had a BMI > 25 (p = 0.007). In the GDM subgroup, maternal height remained significantly higher in those who delivered LGA infants (p = 0.017). In multivariable models, moderate CQI was consistently associated with increased odds of LGA across all models (Model 1: aOR = 1.60 (95% CI: 1.03–2.50), p = 0.037, Model 2: aOR = 1.57 (95% CI: 1.01–2.46), p = 0.046, Model 3: aOR = 1.58 (95% CI: 1.01–2.47), p = 0.044, Model 4 aOR: 1.70; 95% CI: 1.08–2.72; p = 0.023), whereas high CQI was not. In the GDM subgroup, a significant association between high CQI and increased LGA risk was observed in less adjusted models (Model 1 aOR: 6.74; 95% CI: 1.32–56.66; p = 0.039, Model 2 aOR: 6.64; 95% CI: 1.27–57.48; p = 0.044), but this was attenuated and became non-significant in the fully adjusted model (aOR: 3.05; 95% CI: 0.47–30.22; p = 0.28). When examining CQI components individually, no consistent associations were observed. Notably, a higher intake of low-quality carbohydrates (≥50% of energy intake) was significantly associated with increased LGA risk in the total population (aOR: 4.25; 95% CI: 1.53–11.67; p = 0.005). Conclusions: Higher early pregnancy intake of low-quality carbohydrates was associated with an elevated risk of LGA in the general population. However, CQI itself showed a non-linear and inconsistent relationship with LGA, with moderate, but not high, CQI linked to increased risk, particularly in GDM pregnancies, where associations were lost after adjustment. Both carbohydrate quality and quantity evaluations are essential, particularly in high-risk groups, to inform dietary guidance in pregnancy. Full article
(This article belongs to the Special Issue Recent Advances in Maternal and Fetal Health (2nd Edition))
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25 pages, 3349 KiB  
Article
Upregulation of the Antioxidant Response-Related microRNAs miR-146a-5p and miR-21-5p in Gestational Diabetes: An Analysis of Matched Samples of Extracellular Vesicles and PBMCs
by Jovana Stevanović, Ninoslav Mitić, Ana Penezić, Ognjen Radojičić, Daniela Ardalić, Milica Mandić, Vesna Mandić-Marković, Željko Miković, Miloš Brkušanin, Olgica Nedić and Zorana Dobrijević
Int. J. Mol. Sci. 2025, 26(14), 6902; https://doi.org/10.3390/ijms26146902 - 18 Jul 2025
Viewed by 245
Abstract
MicroRNA-based regulatory mechanisms show disturbances related to oxidative stress (OS) interconnected with inflammation (IFM), as well as impairments associated with gestational diabetes (GDM). The aim of this study was to assess the diagnostic and prognostic significance of the OS/IFM-related microRNA in GDM by [...] Read more.
MicroRNA-based regulatory mechanisms show disturbances related to oxidative stress (OS) interconnected with inflammation (IFM), as well as impairments associated with gestational diabetes (GDM). The aim of this study was to assess the diagnostic and prognostic significance of the OS/IFM-related microRNA in GDM by using peripheral blood mononuclear cells (PBMCs) and serum-derived extracellular vesicles (EVs) as biological samples. We selected the known OS/IFM-associated microRNAs miR-146a-5p, miR-155-5p, and miR-21-5p as candidates for our GDM biomarker analysis. Quantitative RT-PCR was employed for relative quantification of the selected microRNAs from paired samples of PBMCs and EVs derived from patients with GDM and healthy controls (n = 50 per group). The expression levels were analyzed for correlations with lipid and glycemic status indicators; metal ion-related parameters; serum thiol content; protein carbonyl and thiobarbituric acid-reactive substances’ (TBARS) levels; glutathione reductase (GR), Superoxide dismutase (SOD), and catalase (CAT) activity; and NRF2 expression. MiR-146a-5p and miR-21-5p were significantly upregulated in both PBMCs and EVs obtained from GDM patients. EVs-miR-21-5p showed a positive correlation with glycemic status in GDM patients, while miR-155-5p from PBMCs demonstrated correlation with iron-related parameters. The expression of selected microRNAs was found to correlate with NRF2 expression and SOD activity. The level of miR-146a-5p negatively correlated with neonatal anthropometric characteristics, while a higher level of PBMCs-miR-21-5p expression was determined in GDM patients with adverse pregnancy outcomes (p = 0.012). Our data demonstrate a disturbance of OS/IFM-microRNAs in GDM and illustrate their potential to serve as indicators of the associated OS-related changes, neonatal characteristics, and adverse pregnancy outcomes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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13 pages, 1017 KiB  
Systematic Review
Systematic Review of Nutritional Guidelines for the Management of Gestational Diabetes Mellitus: A Global Comparison
by Angelo Sirico, Maria Giovanna Vastarella, Eleonora Ruggiero and Luigi Cobellis
Nutrients 2025, 17(14), 2356; https://doi.org/10.3390/nu17142356 - 18 Jul 2025
Viewed by 586
Abstract
Background: Gestational diabetes mellitus (GDM) affects 7–9% of pregnancies worldwide and is associated with adverse maternal and neonatal outcomes. Nutritional therapy is a key component of GDM management. However, inconsistencies exist across international and national guidelines regarding macronutrient distribution, glycemic targets, and micronutrient [...] Read more.
Background: Gestational diabetes mellitus (GDM) affects 7–9% of pregnancies worldwide and is associated with adverse maternal and neonatal outcomes. Nutritional therapy is a key component of GDM management. However, inconsistencies exist across international and national guidelines regarding macronutrient distribution, glycemic targets, and micronutrient supplementation. This systematic review aims to compare updated nutritional recommendations for GDM across major health organizations and identify areas of consensus, divergence, and evidence gaps. Methods: This systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251026194). A comprehensive literature search was performed in PubMed, Scopus, and Google Scholar (concluding March 2025), along with manual searches of official websites of professional health organizations (e.g., ADA, WHO, NICE, IDF). Guidelines published within the last 10 years (or the most relevant national guideline if slightly older), available in English or with access to translation, and including explicit nutritional recommendations for GDM were included. Data were extracted on macronutrient composition, glycemic targets, and micronutrient supplementation, with evaluation of the supporting evidence and regional context, incorporating findings from recent key guideline updates. Results: In total, 12 guidelines met the inclusion criteria. While all guidelines emphasized carbohydrate moderation and adequate fiber intake, significant discrepancies were found in carbohydrate quality recommendations (e.g., low-glycemic index focus vs. total carbohydrate restriction), postprandial glucose targets (e.g., 1-h vs. 2-h measurements and varying thresholds like <120 vs. <140 mg/dL), and the use of non-routine micronutrients such as chromium, selenium, and omega-3 fatty acids (generally lacking endorsement). Recent updates from key bodies like ADA, Diabetes Canada, and KDA largely maintain these core stances but show increasing emphasis on dietary patterns and acknowledgement of CGM technology, without resolving key discrepancies. Cultural adaptability and behavioral counselling strategies were minimally addressed across most guidelines. Conclusions: Despite general agreement on the principal recommendations of nutritional management in GDM, substantial variation persists in specific recommendations, even considering recent updates. Consistent, evidence-based, and culturally adaptable guidelines incorporating implementation strategies are needed to optimize care and reduce disparities in GDM management across regions. Full article
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21 pages, 511 KiB  
Systematic Review
Trimester-Specific Serum Lipid Profiles in Gestational Diabetes Mellitus: A Systematic Review, Meta-Analysis, and Meta-Regression
by Milos Milincic, Andja Cirkovic, Katarina Ivanovic, Stefan Dugalic and Miroslava Gojnic Dugalic
Medicina 2025, 61(7), 1290; https://doi.org/10.3390/medicina61071290 - 17 Jul 2025
Viewed by 321
Abstract
Background and Objectives: Gestational diabetes mellitus (GDM) is a major public health concern associated with adverse maternal and neonatal outcomes. It was found that even physiological pregnancy is followed by a significant shift in serum lipid profile, and even more pronounced in [...] Read more.
Background and Objectives: Gestational diabetes mellitus (GDM) is a major public health concern associated with adverse maternal and neonatal outcomes. It was found that even physiological pregnancy is followed by a significant shift in serum lipid profile, and even more pronounced in GDM pregnancies. We aimed to comprehensively assess lipid parameters among pregnant women with and without GDM. Materials and Methods: A systematic review, covering PubMed, WoS, and SCOPUS until 23 July 2024, with meta-analysis and meta-regression, was conducted, comprising studies measuring TG, TC, LDL-C, HDL-C, VLDL-C, and TG/HDL ratio in pregnant women diagnosed with GDM, and those with normal glucose tolerance. The overall effect size measure was the SMD. NOS and JADAD scales were used for quality assessment, I2 statistics for heterogeneity evaluation, and funnel plots for publication bias inspection. Results: A total of 457 studies were included in the qualitative analysis, and 74, 277, and 122 studies were included in the quantitative analysis for the 1st 2nd, and 3rd trimester, respectively. TG and TG/HDL levels were significantly elevated in all three trimesters (TG: SMD = 0.61, 0.57, and 0.48, p < 0.001 for all, and TG/HDL: SMD = 0.44, 0.66, and 0.49; p < 0.001 for all), while TC and LDL-C levels showed significant increases in the 1st and 2nd trimesters (TC: SMD = 0.38, 0.27, p < 0.001 for both, LDL-C: SMD = 0.33, 0.20, p < 0.001 for both), in pregnant women with GDM compared to those without the condition. Conclusions: GDM is associated with significant lipid abnormalities, particularly elevated TG and decreased HDL-C levels. These lipid changes are most pronounced in the first and second trimesters, highlighting the importance of early detection and management. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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12 pages, 1450 KiB  
Article
Polyhydramnios at Term in Gestational Diabetes: Should We Be Concerned?
by Mercedes Horcas-Martín, Tania Luque-Patiño, Claudia Usandizaga-Prat, Elena Díaz-Fernández, Victoria Melero-Jiménez, Luis Vázquez-Fonseca, Francisco Visiedo, José Román Broullón-Molanes, Rocío Quintero-Prado and Fernando Bugatto
Children 2025, 12(7), 920; https://doi.org/10.3390/children12070920 - 11 Jul 2025
Viewed by 455
Abstract
Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM [...] Read more.
Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article
(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Their Impact on Neonatal Outcomes)
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15 pages, 527 KiB  
Article
Some Levels of Plasma Free Fatty Acids and Amino Acids in the Second Trimester Are Linked to Gestational Diabetes and Are Predictive of Persisting Impaired Glucose Tolerance After Delivery
by Vendula Bartáková, Anna Pleskačová, Lukáš Pácal, Monika Skrutková Langmajerová, Jindra Smutná, Katarína Chalásová, Veronika Eclerová, Zdeněk Glatz, Kateřina Kaňková and Josef Tomandl
J. Clin. Med. 2025, 14(13), 4744; https://doi.org/10.3390/jcm14134744 - 4 Jul 2025
Viewed by 310
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) represents an increased metabolic risk in future life for both mother and child. We hypothesize free fatty acids (FFAs) and amino acids (AAs) disturbances in plasma during second trimester might be indicating high risk of persisting glucose intolerance [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) represents an increased metabolic risk in future life for both mother and child. We hypothesize free fatty acids (FFAs) and amino acids (AAs) disturbances in plasma during second trimester might be indicating high risk of persisting glucose intolerance (PGI). The aim of study was to determine plasma FFAs and AAs during pregnancy in women with normal pregnancy and GDM and also in post-GDM women with PGI after delivery and to find potential association of altered FFAs and AAs profile with adverse peripartal outcomes and PGI after GDM. Material and Methods: A total of 54 pregnant women were included in the study. Of those 34 participants had GDM. PGI was diagnosed by oGTT up to one year after delivery. Plasma FFAs were determined using GC-FID and plasma AAs levels were determined using CE-MS method. Results: Decreased levels of tetradecanoic acid and several AAs were found in GDM group during pregnancy. Oleic and docosahexaenoic acid correlated positively while almost all AAs negatively correlated with oGTT values in the pregnancy (all p < 0.05, Spearman). Logistic regression model (using AAs, FFAs and BMI) identified higher citrulline and glutamate levels and lower tetradecenoic acid and choline as the best predictors for postpartum PGI. Some differences in AA levels were detected in women with macrosomic babies. Conclusions: Data support a possible link between GDM development and PGI after delivery and selected metabolite levels. The predictive potential of plasma FFAs and AAs levels on a diabetes risk in future life requires further validation. Full article
(This article belongs to the Special Issue Gestational Diabetes: Cutting-Edge Research and Clinical Practice)
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10 pages, 388 KiB  
Article
Evaluating the Predictive Value of HOMA-IR in Gestational Diabetes: A Case–Control Study from Romania
by Ait el Haj Iman, Cristina Onel, Gheorghe Furau, Cristian Furau, Roxana Furau, Mihai Lucan, Mircea Sandor, Liliana Sachelarie and Anca Huniadi
Diagnostics 2025, 15(13), 1704; https://doi.org/10.3390/diagnostics15131704 - 3 Jul 2025
Viewed by 526
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy, associated with increased risks for both maternal and fetal complications. Insulin resistance plays a central role in its pathophysiology. This study aimed to evaluate the predictive value of the Homeostatic Model [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy, associated with increased risks for both maternal and fetal complications. Insulin resistance plays a central role in its pathophysiology. This study aimed to evaluate the predictive value of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in diagnosing GDM and to explore its correlation with clinical and anthropometric parameters in a Romanian population. Methods: A retrospective case–control study was conducted on 320 pregnant women between 24 and 28 weeks of gestation. Based on ADA criteria, participants were divided into 160 with GDM and 160 controls, matched by age and gestational week. Fasting glucose, insulin, BMI, and blood pressure were assessed. HOMA-IR and HOMA-β were calculated. Statistical analyses included t-tests, Pearson correlation, and logistic regression. Results: HOMA-IR was significantly higher in the GDM group (2.9 vs. 1.8; p < 0.001). It correlated with fasting insulin (r = 0.85, p < 0.001), fasting glucose (r = 0.65, p < 0.001), BMI (r = 0.60, p < 0.001), and systolic blood pressure (r = 0.42, p < 0.001). Logistic regression identified HOMA-IR as an independent predictor of GDM (OR = 2.4, 95% CI: 1.6–3.5, p < 0.001), along with BMI (p = 0.01) and maternal age (p = 0.05). Conclusions: HOMA-IR is significantly associated with GDM and may enhance mid-gestational risk assessment when combined with clinical and anthropometric measures. Further studies are needed to validate its predictive accuracy in broader populations. Full article
(This article belongs to the Special Issue Insights into Perinatal Medicine and Fetal Medicine—2nd Edition)
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14 pages, 520 KiB  
Review
The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
by Antonia Varthaliti, Vasilios Lygizos, Maria Fanaki, Vasilios Pergialiotis, Angeliki Papapanagiotou, Kalliopi Pappa, Marianna Theodora, Maria Anastasia Daskalaki, Panos Antsaklis and George Daskalakis
Biomedicines 2025, 13(7), 1627; https://doi.org/10.3390/biomedicines13071627 - 2 Jul 2025
Viewed by 549
Abstract
Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first [...] Read more.
Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications. Full article
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15 pages, 1159 KiB  
Article
Maternal and Fetal–Neonatal Complications of Romanian Women with Gestational Diabetes: A Retrospective Comparative Study
by Adriana Gherbon, Mirela Frandes, Corina Dalia Toderescu, Darius Dirpes, Romulus Timar, Marioara Neagu Nicula, Calin Dascau, Razvan Daniluc and Bogdan Timar
Medicina 2025, 61(7), 1190; https://doi.org/10.3390/medicina61071190 - 30 Jun 2025
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Abstract
Background and Objectives: Gestational diabetes mellitus (GDM) is a complex condition characterized by metabolic disorders of blood glucose that significantly impact the health of both mother and fetus. The objectives of this study were to assess the prevalence and risk factors for maternal [...] Read more.
Background and Objectives: Gestational diabetes mellitus (GDM) is a complex condition characterized by metabolic disorders of blood glucose that significantly impact the health of both mother and fetus. The objectives of this study were to assess the prevalence and risk factors for maternal and fetal–neonatal complications in women with GDM, comparing them to a control group (pregnant women without GDM) and pregnant women with type 1 diabetes mellitus (T1DM) or type 2 diabetes (T2DM). Materials and Methods: A retrospective observational study was conducted with 1418 pregnant women (279 with GDM, 74 with T1DM, 107 with T2DM, and 958 in the control group). The retrospective data included information on demographics, diagnostic test results, the medical history of pregnant women, treatments administered, identified complications, and other relevant variables for the study’s purpose. Results: Significant differences were found regarding maternal and neo-fetal complications between GDM and the control group in terms of abortion, pregnancy-induced hypertension, and increased fetal weight (macrosomia). Women with T1DM and T2DM showed a higher rate of abortion, premature birth, and an APGAR score of <7 at 5 min compared to those with GDM, and for T1DM, there was a higher rate of fetal mortality than in GDM cases. The primary risk factors for maternal complications included age OR = 1.03 (95% CI: 1.01–1.05, p = 0.002), obesity OR = 2.37 (95% CI: 1.42–3.94, p < 0.001), and chronic hypertension OR = 2.51 (95% CI: 1.26–5.01, p = 0.009). Age and obesity were also significant cofactors for maternal complications. Furthermore, the main significant risk factors for fetal–neonatal complications were obesity OR = 2.481 (95% CI:1.49–4.12, p < 0.001) and chronic hypertension OR = 2.813 (95% CI:1.44–5.49, p = 0.002), both independently and as cofactors. Conclusions: We found that obesity and chronic hypertension are risk factors for both maternal and fetal–neonatal complications. It is essential to prevent and adequately treat these two factors among pregnant women to avoid the onset of GDM. Additionally, screening for GDM is necessary to prevent maternal and fetal complications. Our results highlight the importance of specialized medical care and tailored management protocols in mitigating risks and ensuring positive outcomes for both mother and child during and after childbirth. Full article
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11 pages, 372 KiB  
Review
Role of FGF-19, FGF-21 and FGF-23 in Fetal and Neonatal Growth
by Anna Rzewuska-Fijałkowska, Wojciech Kwaśniewski and Tomasz Gęca
J. Clin. Med. 2025, 14(13), 4520; https://doi.org/10.3390/jcm14134520 - 26 Jun 2025
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Abstract
Background: The Fibroblast Growth Factor (FGF) 19 subfamily plays a key role in the regulation of metabolic and growth processes, and their dysregulation can lead to fetal growth disorders, such as small for gestational age (SGA) and large for gestational age (LGA), as [...] Read more.
Background: The Fibroblast Growth Factor (FGF) 19 subfamily plays a key role in the regulation of metabolic and growth processes, and their dysregulation can lead to fetal growth disorders, such as small for gestational age (SGA) and large for gestational age (LGA), as well as to pathogenesis and development of gestational diabetes and gestational hypertension. Methods: We conducted a narrative review using the PRISMA2020 statement. Two electronic databases were searched: PubMed and Web of Science until October 2024. The search terms were as follows: (FGF-21 OR fibroblast growth factor-21 OR FGF-23 OR fibroblast growth factor-23 OR FGF-19 OR fibroblast growth factor-19) AND (human fetus development OR fetal growth OR infancy). We only included original papers that analysed the effect of FGF-19,21,23 on pre- and postnatal development. Results: Only 6 out of 203 studies met the inclusion criteria. There were higher concentrations of FGF-21 among patients with gestational diabetes mellitus (GDM) compared to healthy females, but no differences were found in FGF-21 values in newborn’s umbilical cord blood. Interestingly, higher FGF-21 concentrations were observed in females than males born to patients with GDM. FGF-19 was linked to fetal development by its association with chronic insulin secretion levels during fetal life, particularly in female newborns, but no significant correlation with GDM was found. The evaluation of the role of FGF-23 has shown that its low level could be related to gestational hypertension and fetal growth restriction. Conclusions: In conclusion, all the studies discussed suggest that FGF-19 subfamily factors may play an important role in fetal and neonatal growth and development, particularly in pregnancies complicated by metabolic disorders, such as gestational diabetes or gestational hypertension. Differences in FGF-19 and FGF-21 concentrations based on gender and gestational disorders suggest the need for further research in order to fully understand the effects of these proteins and their potential clinical applications. Full article
(This article belongs to the Special Issue New Challenges in Maternal-Fetal Medicine)
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16 pages, 562 KiB  
Article
Impact of Sucrose Consumption on the Metabolic, Immune, and Redox Profile of Mice with Gestational Diabetes Mellitus
by Cristian Ángel Rosales-Gómez, Beatriz Elina Martínez-Carrillo, Ana Laura Guadarrama-López, Aldo Arturo Reséndiz-Albor, Ivonne Maciel Arciniega-Martínez and Efrén Aguilar-Rodríguez
Life 2025, 15(7), 989; https://doi.org/10.3390/life15070989 - 20 Jun 2025
Viewed by 1150
Abstract
Carbohydrate consumption during pregnancy represents an important source of energy; its consumption, however, can cause gestational diabetes mellitus (GDM), body weight gain, inflammation, increased glucose transport to the fetus, adiposity, and a risk of macrosomia. The objective was to research the impact of [...] Read more.
Carbohydrate consumption during pregnancy represents an important source of energy; its consumption, however, can cause gestational diabetes mellitus (GDM), body weight gain, inflammation, increased glucose transport to the fetus, adiposity, and a risk of macrosomia. The objective was to research the impact of sucrose consumption during pregnancy on the metabolic, immune, and redox profile in female mice with GDM. A total of 24 female CD1 mice were used, divided into two groups: Control and GDM. Each group was subdivided into two subgroups: (a) Without sucrose and (b) With sucrose. The females were mated, and, once pregnancy was confirmed, GDM was induced by administering 230 mg/kg of streptozotocin subcutaneously. GDM was confirmed by glucose ≥ 200 mg/dL and the presence of polyphagia, polydipsia, and change in body weight. Metabolic, immune, and redox profile parameters were determined. Sucrose consumption groups increase HOMA-IR and the secretion of insulin, adiponectin, and leptin; it also increased the secretion of proinflammatory cytokines and the production of IgA and IgG antibodies, decreased the activity of the Glutathione Reductase enzyme, and increased the production of TBARS and AGE. High sucrose consumption increases the inflammatory response mediated mainly by CD8+ lymphocytes and the production of proinflammatory cytokines; it can trigger a compensatory humoral response and alter redox mechanisms, causing a state of Oxidant Stress. Full article
(This article belongs to the Special Issue Management of Patients with Diabetes)
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