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Metabolites
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Glucose Metabolism in Pregnancy
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Glucose Metabolism in Pregnancy

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 May 2025) | Viewed by 9925

Special Issue Editor

Dr. Moen Gunn-Helen

E-Mail Website
Guest Editor
Institute for Molecular Bioscience, The University of Queensland, Brisbane, St Lucia, QLD 4072, Australia
Interests: pregnancy; maternal environmental exposures; glucose metabolism

Special Issue Information

Dear Colleagues,

Maternal health before and during pregnancy is important for the future health of both mother and child. For instance, the offspring of mothers with gestational diabetes have an increased risk of birth complications associated with increased birthweight and adiposity, such as shoulder dystocia, neonatal hypoglycemia, and obesity, as well as for developing metabolic syndrome, type 2 diabetes, and cardiovascular disease in adult life. It is also well known that women with gestational diabetes are at high risk of developing type 2 diabetes and other cardiometabolic diseases later in life, and it has been estimated that around 50% of the women diagnosed with gestational diabetes will develop type 2 diabetes within 5–10 years. In this Special Issue, I sincerely welcome review articles, as well as clinical and original research articles studying glucose metabolism in pregnancy and gestational diabetes. This Special Issue will also be dedicated to the consequences related to gestational diabetes for both mother and child.

Dr. Moen Gunn-Helen
Guest Editor

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Keywords

  • glucose metabolism
  • gestational diabetes
  • pregnancy
  • diabetes
  • glucose

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Published Papers (6 papers)

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Research

Jump to: Review

14 pages, 3810 KiB  
Article
Methimazole-Induced Hypothyroidism Increases the Content of Glycogen and Changes the Expression of LDH, GLUT4, and Aromatase in the Pregnant Uterus of Rabbits
by Marlen Espindola-Lozano, Maribel Méndez-Tepepa, Marlenne Castillo-Romano, Rubicela Rojas-Juárez, Leticia Nicolás-Toledo, Jorge Rodríguez-Antolín, Francisco Castelán and Estela Cuevas-Romero
Metabolites 2025, 15(2), 82; https://doi.org/10.3390/metabo15020082 - 30 Jan 2025
Viewed by 763
Abstract
Objective: To determine the impact of hypothyroidism on uterine glycogen accumulation during pregnancy. Methods: Non-pregnant and pregnant (days 5, 10, and 20) rabbits were grouped into control and methimazole (MMI) groups. In rabbits, serum concentrations of thyroxine (T4), triiodothyronine, glucose, insulin, [...] Read more.
Objective: To determine the impact of hypothyroidism on uterine glycogen accumulation during pregnancy. Methods: Non-pregnant and pregnant (days 5, 10, and 20) rabbits were grouped into control and methimazole (MMI) groups. In rabbits, serum concentrations of thyroxine (T4), triiodothyronine, glucose, insulin, progesterone, and estradiol were quantified. In uterine inter- and implantation sites, the glycogen content and expression of lactate dehydrogenase (LDH), GLUT4, and aromatase were quantified via Western blot. Fetuses’ characteristics at 20 days of pregnancy were analyzed. Two-way ANOVA was used to compare variables between groups. Results: Pregnancy reduced T4 concentrations but not T3. In virgin groups, MMI treatment significantly reduced the concentrations of T4 and T3 and increased the expression of GLUT4 and aromatase in the uterus compared to the control group. In pregnant groups, T4, T3, glucose, insulin, progesterone, and estradiol levels were similar between control and MMI-treated rabbits. Compared to controls, MMI treatment in pregnant rabbits (a) reduced GLUT4 expression on inter-implantation sites on day 5; (b) increased glycogen content on implantation sites but reduced GLUT4 expression on inter-and implantation sites on day 10; (c) increased glycogen content and LDH and aromatase expression but reduced GLUT4 on inter-implantation sites; and (d) increased glycogen content and the expression of LDH, GLUT4, and aromatase on day 20 on implantation sites. Moreover, the fetus characteristics were similar between groups. Conclusions: MMI-induced hypothyroidism is associated with changes in the uterine content of glycogen and the expression of LDH, GLUT4, and aromatase during pregnancy. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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12 pages, 481 KiB  
Article
Improvements in Insulin Resistance and Glucose Metabolism Related to Breastfeeding Are Not Mediated by Subclinical Inflammation
by Julia Martins de Oliveira, Patrícia Médici Dualib, Alexandre Archanjo Ferraro, Rosiane Mattar, Sérgio Atala Dib and Bianca de Almeida-Pititto
Metabolites 2024, 14(11), 608; https://doi.org/10.3390/metabo14110608 - 9 Nov 2024
Viewed by 1542
Abstract
Background: Lactation is known to improve insulin resistance, but this phenomenon remains poorly understood. Our goal was to evaluate whether subclinical inflammation could mediate the association between breastfeeding (BF) and improvement in glucose metabolism and markers of insulin resistance (MIRs) in the postpartum. [...] Read more.
Background: Lactation is known to improve insulin resistance, but this phenomenon remains poorly understood. Our goal was to evaluate whether subclinical inflammation could mediate the association between breastfeeding (BF) and improvement in glucose metabolism and markers of insulin resistance (MIRs) in the postpartum. Methods: A total of 95 adult women (≥18 years) with a BMI ≥ 25 kg/m2 from the outpatient clinic of the Federal University of São Paulo were followed from early pregnancy until 60 to 180 days postpartum. The patients were divided based on their BF status: BF and non-BF groups. A latent variable termed SubInf was created incorporating inflammation-related biomarkers: adiponectin, E-selectin, branched-chain amino acids, zonulin, copeptin, and lipopolysaccharides. The association of BR with MIRs in the postpartum was evaluated through linear regression analysis, and mediation analysis was performed to evaluate the role of SubInf in this association. Results: The groups were similar regarding gestational diabetes mellitus (GDM) prevalence, pre-gestational BMI, caloric intake, physical activity, and postpartum weight loss. The BF group presented lower levels of triglycerides (TGs), fasting glucose, fasting insulin, TG/HDLcholesterol ratio (TG/HDL), TyG index, and HOMA-IR compared to the non-BF group. A linear regression analysis adjusted for scholarity, parity, pre-gestational BMI, GDM, weight gain during pregnancy, and mode of delivery revealed an inverse association between BF and fasting glucose [−6.30 (−10.71 to −1.89), p = 0.005), HOMA-IR [−0.28 (−0.50 to −0.05), p = 0.017], TyG index [−0.04 (−0.06 to −0.01), p = 0.002], and TG/HDL ratio [−0.23 (−0.46 to −0.01), p = 0.001]. In the mediation analysis, SubInf did not mediate the indirect effect of BF on MIRs. Conclusions: In overweight and obese women, an association between BF and improvement in MIRs in the postpartum was seen, corroborating that BF should be stimulated, especially in these cardiometabolic high-risk women. Subclinical inflammation did not seem to mediate this association. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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16 pages, 273 KiB  
Article
Metabolic and Immune Parameters in Pregnant Women with Impaired Glucose Metabolism—A Pilot Study
by Jelena Omazić, Andrijana Muller, Blaž Dumančić, Mirta Kadivnik, Jasna Aladrović, Lana Pađen, Kristina Kralik, Nikolina Brkić, Blaženka Dobrošević, Barbara Vuković and Jasenka Wagner
Metabolites 2024, 14(10), 551; https://doi.org/10.3390/metabo14100551 - 16 Oct 2024
Viewed by 1177
Abstract
Gestational diabetes mellitus (GDM) is a public health problem with increasing prevalence. Analyses of metabolic and immune profiles have great potential for discovering new markers and mechanisms related to the development of GDM. We monitored 61 pregnant women during the first and third [...] Read more.
Gestational diabetes mellitus (GDM) is a public health problem with increasing prevalence. Analyses of metabolic and immune profiles have great potential for discovering new markers and mechanisms related to the development of GDM. We monitored 61 pregnant women during the first and third trimesters of pregnancy, including 13 pregnant women with GDM, 14 pregnant women with elevated glucose in the first trimester and 34 healthy pregnant women. A number of metabolic and immunological parameters were measured, including glucose, insulin, lipid status, fatty acids, lymphocyte profile, adiponectin, IL-6, IL-10 and TNF-a. A higher number of T-helper lymphocytes and a higher ratio of helper/cytotoxic lymphocytes was found in the control group in the first trimester of pregnancy. Pregnant women whose glucose threshold values were measured in the first trimester, but who did not develop GDM, showed a higher percentage of neutrophils and a lower percentage of lymphocytes in the third trimester. Differences in polyunsaturated fatty acids levels were observed between healthy pregnant women and those with glucose metabolism disorders in the first trimester of pregnancy. The results of this pilot study demonstrate that there are differences in the profiles of T lymphocytes, NK cells and polyunsaturated fatty acids between the examined groups of pregnant women, which can serve as a direction for future research. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
12 pages, 1620 KiB  
Article
Adipose Tissue Insulin Resistance in South Asian and Nordic Women after Gestational Diabetes Mellitus
by Ahalya Anita Suntharalingam Kvist, Archana Sharma, Christine Sommer, Elisabeth Qvigstad, Hanne Løvdal Gulseth, Stina Therese Sollid, Ingrid Nermoen, Naveed Sattar, Jason Gill, Tone Møller Tannæs, Kåre Inge Birkeland and Sindre Lee-Ødegård
Metabolites 2024, 14(5), 288; https://doi.org/10.3390/metabo14050288 - 18 May 2024
Cited by 3 | Viewed by 2336
Abstract
South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This [...] Read more.
South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1–3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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Review

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19 pages, 1871 KiB  
Review
Thioredoxin-Interacting Protein (TXNIP) in Gestational Diabetes Mellitus
by Ioanna Kokkinopoulou and Anna Papadopoulou
Metabolites 2025, 15(6), 351; https://doi.org/10.3390/metabo15060351 - 26 May 2025
Viewed by 126
Abstract
Background: Thioredoxin-interacting protein (TXNIP) is a major inhibitor of the thioredoxin (TRX) antioxidant system and an important player in the development and aggravation of intracellular oxidative stress. Although first recognized as a metabolic regulator, recent studies have identified the multifaceted role of this [...] Read more.
Background: Thioredoxin-interacting protein (TXNIP) is a major inhibitor of the thioredoxin (TRX) antioxidant system and an important player in the development and aggravation of intracellular oxidative stress. Although first recognized as a metabolic regulator, recent studies have identified the multifaceted role of this protein in other molecular pathways involving inflammation, apoptosis, and glucose metabolism. Methods: This review aims to highlight the importance of TXNIP in diabetes-related pathophysiology and explore the existing evidence regarding TXNIP’s role in GDM-associated pathogenetic mechanisms, revealing common regulatory pathways. Results: Among other complex diseases, TXNIP has been found upregulated in diabetic pancreatic beta cells, thus contributing to diabetes pathogenesis and its related complications. In addition, depletion of TXNIP has been shown to decrease the negative consequences of excessive stress in various cellular systems and diseases, pointing towards a potential therapeutic target. In line with these findings, TXNIP has been investigated in the pathogenesis of Gestational Diabetes Mellitus (GDM), a common pregnancy complication affecting the mother and the neonate. Overexpression of TXNIP has been found in GDM placentas or trophoblast cell lines mimicking GDM conditions and has been associated with key dysregulated mechanisms of GDM pathophysiology, like oxidative stress, inflammation, apoptosis, impaired autophagy, altered trophoblast behavior, and placental morphology. Interestingly, TXNIP has been found upregulated in GDM maternal serum and downregulated in umbilical cord blood, indicating potential compensatory protective mechanisms to GDM-related oxidative stress. Conclusions: Due to its contribution to the regulation of critical cellular processes such as inflammation, metabolism, and apoptosis, TXNIP finds its place in the pathophysiology of gestational diabetes through a currently limited number of scientific reports. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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32 pages, 1638 KiB  
Review
Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy
by Caroline Brito Nunes, Maria Carolina Borges, Rachel M. Freathy, Deborah A. Lawlor, Elisabeth Qvigstad, David M. Evans and Gunn-Helen Moen
Metabolites 2024, 14(9), 508; https://doi.org/10.3390/metabo14090508 - 20 Sep 2024
Cited by 1 | Viewed by 2684
Abstract
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion [...] Read more.
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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