{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:24:36Z","timestamp":1793039076723,"version":"4.5.0"},"reference-count":123,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["129844, 129897, 120832"],"award-info":[{"award-number":["129844, 129897, 120832"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["Baseline funding"],"award-info":[{"award-number":["Baseline funding"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Clin. Diabetes Healthc."],"abstract":"<jats:p>Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been suggested that the frequency and severity of pregnancy complications are linked to the degree of hyperglycemia. Epigenetic mechanisms reflect gene-environment interactions and have emerged as key players in metabolic adaptation to pregnancy and the development of complications. DNA methylation, the best characterized epigenetic mechanism, has been reported to be dysregulated during various pregnancy complications, including pre-eclampsia, hypertension, diabetes, early pregnancy loss and preterm birth. The identification of altered DNA methylation patterns may serve to elucidate the pathophysiological mechanisms that underlie the different types of maternal diabetes during pregnancy. This review aims to provide a summary of existing knowledge on DNA methylation patterns in pregnancies complicated by pregestational type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Four databases, CINAHL, Scopus, PubMed and Google Scholar, were searched for studies on DNA methylation profiling in pregnancies complicated with diabetes. A total of 1985 articles were identified, of which 32 met the inclusion criteria and are included in this review. All studies profiled DNA methylation during GDM or impaired glucose tolerance (IGT), while no studies investigated T1DM or T2DM. We highlight the increased methylation of two genes, <jats:italic>Hypoxia\u2010inducible Factor\u20103\u03b1 (HIF3\u03b1)<\/jats:italic> and <jats:italic>Peroxisome Proliferator-activated Receptor Gamma-coactivator-Alpha (PGC1-\u03b1)<\/jats:italic>, and the decreased methylation of one gene, <jats:italic>Peroxisome Proliferator Activated Receptor Alpha (PPAR\u03b1)<\/jats:italic>, in women with GDM compared to pregnant women with normoglycemia that were consistently methylated across diverse populations with varying pregnancy durations, and using different diagnostic criteria, methodologies and biological sources. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. Furthermore, these genes may provide insight into the pathways that are epigenetically influenced during maternal diabetes and which should be prioritized and replicated in longitudinal studies and in larger populations to ensure their clinical applicability. Finally, we discuss the challenges and limitations of DNA methylation analysis, and the need for DNA methylation profiling to be conducted in different types of maternal diabetes in pregnancy.<\/jats:p>","DOI":"10.3389\/fcdhc.2022.982665","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T07:39:31Z","timestamp":1663832371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["The role of maternal DNA methylation in pregnancies complicated by gestational diabetes"],"prefix":"10.3389","volume":"3","author":[{"given":"Stephanie","family":"Dias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarryn","family":"Willmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaiya","family":"Adam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pheiffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2017.1387893","article-title":"Short- and long-term consequences for offspring exposed to maternal diabetes: A review","volume":"32","author":"Burlina","year":"2019","journal-title":"J. Matern Fetal Neonatal Med."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.09.004","article-title":"Gestational diabetes mellitus: Mechanisms, treatment, and complications","volume":"29","author":"Johns","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2018.01.002","article-title":"Pregestational diabetes in pregnancy","volume":"45","author":"Sugrue","year":"2018","journal-title":"Obstet Gynecol Clin. North Am."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-s206","article-title":"Increasing prevalence of gestational diabetes mellitus: A public health perspective","author":"Ferrara","year":"2007","journal-title":"Diabetes Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"899","DOI":"10.2337\/dc07-2345","article-title":"Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially\/ethnically diverse population of pregnant women, 1999-2005","volume":"31","author":"Lawrence","year":"2008","journal-title":"Diabetes Care"},{"key":"B6","volume-title":"IDF Diabetes Atlas, 10th edn.","year":"2021"},{"key":"B7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12884-020-2759-8","article-title":"Effects of gestational diabetes mellitus on risk of adverse maternal outcomes: A prospective cohort study in Northwest Ethiopia","volume":"20","author":"Muche","year":"2020","journal-title":"BMC Pregnancy Childbirth"},{"key":"B8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1758-5996-4-41","article-title":"Adverse pregnancy outcomes in women with diabetes","volume":"4","author":"Negrato","year":"2012","journal-title":"Diabetol. Metab. Syndrome"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2008.02431.x","article-title":"Outcomes of pregnancies in women with pre-gestational diabetes mellitus and gestational diabetes mellitus; a population-based study in new south Wales, Australia, 1998-2002","volume":"25","author":"Shand","year":"2008","journal-title":"Diabetes Med."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2017.1387893","article-title":"Short-and long-term consequences for offspring exposed to maternal diabetes: a review","volume":"32","author":"Burlina","year":"2019","journal-title":"J. Maternal-Fetal Neonatal Med."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2015.04.009","article-title":"Diabetes in pregnancy","volume":"29","author":"McCance","year":"2015","journal-title":"Best Pract. Research: Clin. Obstetrics Gynaecol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2014.08.004","article-title":"The offspring of the diabetic mother \u2013 short- and long-term implications","volume":"29","author":"Mitanchez","year":"2015","journal-title":"Best Pract. Res. Clin. Obstetrics Gynaecol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jdiacomp.2013.08.009","article-title":"Pre-gestational versus gestational diabetes: a population based study on clinical and demographic differences","volume":"28","author":"Fong","year":"2014","journal-title":"J. Diabetes Complications"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene expression","volume":"105","author":"Gibney","year":"2010","journal-title":"Heredity."},{"key":"B15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1159\/000439488","article-title":"Development, epigenetics and metabolic programming","volume":"85","author":"Godfrey","year":"2016","journal-title":"Nestle Nutr. Inst Workshop Ser."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/321209a0","article-title":"CpG-rich islands and the function of DNA methylation","volume":"321","author":"Bird","year":"1986","journal-title":"Nature."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013730","article-title":"Correlation of global and gene-specific DNA methylation in maternal-infant pairs","volume":"5","author":"Kile","year":"2010","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cjca.2012.10.023","article-title":"Epigenetics and cardiovascular disease","volume":"29","author":"Webster","year":"2013","journal-title":"Can. J. Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"E148","DOI":"10.3390\/genes8060148","article-title":"CpG and non-CpG methylation in epigenetic gene regulation and brain function","volume":"8","author":"Jang","year":"2017","journal-title":"Genes (Basel)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2015.11.021","article-title":"Differential DNA methylation of microRNAs within promoters, intergenic and intragenic regions of type 2 diabetic, pre-diabetic and non-diabetic individuals","volume":"49","author":"Pheiffer","year":"2016","journal-title":"Clin. Biochem."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036278","article-title":"Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes","volume":"7","author":"Fradin","year":"2012","journal-title":"PLoS One"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4161\/epi.21238","article-title":"Epigenetics: The missing link to understanding \u03b2-cell dysfunction in the pathogenesis of type 2 diabetes","volume":"7","author":"Gilbert","year":"2012","journal-title":"Epigenetics."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.583","article-title":"Methylation of HIF3\u03b1 promoter CpG islands contributes to insulin resistance in gestational diabetes mellitus","volume":"7","author":"Zhang","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2020.1816774","article-title":"Cell-free DNA methylation and transcriptomic signature prediction of pregnancies with adverse outcomes","volume":"16","author":"Del Vecchio","year":"2021","journal-title":"Epigenetics."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12634","article-title":"Hypertensive disorders of pregnancy and DNA methylation in newborns","volume":"74","author":"Kazmi","year":"2019","journal-title":"Hypertension."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1177\/1933719113492206","article-title":"Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity","volume":"21","author":"Nomura","year":"2014","journal-title":"Reprod. Sci."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.738962","article-title":"DNA Methylation and recurrent pregnancy loss: A mysterious compass","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"108690","DOI":"10.1016\/j.diabres.2021.108690","article-title":"Exposure to gestational diabetes mellitus (GDM) alters DNA methylation in placenta and fetal cord blood","volume":"174","author":"Awamleh","year":"2021","journal-title":"Diabetes Res. Clin. Practice"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1160","article-title":"Placental adiponectin gene DNA methylation levels are associated with mothers\u2019 blood glucose concentration","volume":"61","author":"Bouchard","year":"2012","journal-title":"Diabetes."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0289","article-title":"Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus","volume":"62","author":"El Hajj","year":"2013","journal-title":"Diabetes."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv013","article-title":"Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring","volume":"24","author":"Finer","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4161\/epi.26554","article-title":"Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal metabolic status","volume":"8","author":"Houde","year":"2013","journal-title":"Epigenetics."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4161\/epi.25578","article-title":"Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases","volume":"8","author":"Ruchat","year":"2013","journal-title":"Epigenetics."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140688","article-title":"Placental DNA methylation of peroxisome-proliferator-activated receptor-\u03b3 co-activator-1\u03b1 promoter is associated with maternal gestational glucose level","volume":"129","author":"Xie","year":"2015","journal-title":"Clin. Science"},{"key":"B35","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B36","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13148-015-0116-y","article-title":"Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex","volume":"7","author":"Binder","year":"2015","journal-title":"Clin. Epigenet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1024","article-title":"Leptin gene epigenetic adaptation to impaired glucose metabolism during pregnancy","volume":"33","author":"Bouchard","year":"2010","journal-title":"Diabetes Care"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13432","article-title":"Placental maternally expressed gene 3 differentially methylated region methylation profile is associated with maternal glucose concentration and newborn birthweight","volume":"12","author":"Chen","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"B39","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13148-016-0239-9","article-title":"PPARGC1\u03b1 gene DNA methylation variations in human placenta mediate the link between maternal hyperglycemia and leptin levels in newborns","volume":"8","author":"C\u00f4t\u00e9","year":"2016","journal-title":"Clin. epigenetics"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcma.2017.06.027","article-title":"Analysis of whole genome-wide methylation and gene expression profiles in visceral omental adipose tissue of pregnancies with gestational diabetes mellitus","volume":"81","author":"Deng","year":"2018","journal-title":"J. Chin. Med. Assoc."},{"key":"B41","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2217\/epi.14.3","article-title":"Epigenetic dysregulation of the IGF system in placenta of newborns exposed to maternal impaired glucose tolerance","volume":"6","author":"Desgagn\u00e9","year":"2014","journal-title":"Epigenomics."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235828","article-title":"Altered genome-wide DNA methylation in peripheral blood of south African women with gestational diabetes mellitus","volume":"20","author":"Dias","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2018.1539770","article-title":"Global DNA methylation profiling in peripheral blood cells of south African women with gestational diabetes mellitus","volume":"24","author":"Dias","year":"2019","journal-title":"Biomarkers."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0248694","article-title":"Adiponectin DNA methylation in south African women with gestational diabetes mellitus: Effects of HIV infection","volume":"16","author":"Dias","year":"2021","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1177\/1933719115570903","article-title":"Early pregnancy maternal blood DNA methylation in repeat pregnancies and change in gestational diabetes mellitus status-a pilot study","volume":"22","author":"Enquobahrie","year":"2015","journal-title":"Reprod. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13148-017-0329-3","article-title":"Epigenetic signatures of gestational diabetes mellitus on cord blood methylation","volume":"9","author":"Haertle","year":"2017","journal-title":"Clin. Epigenetics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"132\u201341","DOI":"10.1017\/S2040174414000038","article-title":"Placental lipoprotein lipase DNA methylation levels are associated with gestational diabetes mellitus and maternal and cord blood lipid profiles","volume":"5","author":"Houde","year":"2014","journal-title":"J Developmental Origins Health Dis"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.07.034","article-title":"Genome-wide DNA methylation variation in maternal and cord blood of gestational diabetes population","volume":"132","author":"Kang","year":"2017","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00222","article-title":"Association of interleukin-10 methylation levels with gestational diabetes in a Taiwanese population","volume":"9","author":"Kang","year":"2018","journal-title":"Front. IN Genet."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2021-002539","article-title":"DNA Methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks","volume":"10","author":"Kasuga","year":"2022","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"B51","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13148-018-0567-z","article-title":"Alterations of adiponectin gene expression and DNA methylation in adipose tissues and blood cells are associated with gestational diabetes and neonatal outcome","volume":"10","author":"Ott","year":"2018","journal-title":"Clin. Epigenetics"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2020.1805695","article-title":"Altered SOCS3 DNA methylation within exon 2 is associated with increased mRNA expression in visceral adipose tissue in gestational diabetes","volume":"16","author":"Rancourt","year":"2021","journal-title":"Epigenetics."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-016-0247-9","article-title":"Increased global placental DNA methylation levels are associated with gestational diabetes","volume":"8","author":"Reichetzeder","year":"2016","journal-title":"Clin. Epigenet."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1398666","article-title":"DNA Methylation profiles in placenta and its association with gestational diabetes mellitus","volume":"123","author":"Rong","year":"2015","journal-title":"Exp. Clin. Endocrinol. Diab"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.05.010","article-title":"Altered expression of PGC-1alpha and PDX1 and their methylation status are associated with fetal glucose metabolism in gestational diabetes mellitus","volume":"501","author":"Wang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2016.1166321","article-title":"Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies","volume":"13","author":"Wu","year":"2018","journal-title":"Epigenetics."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2019.1609929","article-title":"Epigenetic alteration of rho guanine nucleotide exchange factor 11 (ARHGEF11) in cord blood samples in macrosomia exposed to intrauterine hyperglycemia","volume":"34","author":"Yan","year":"2021","journal-title":"J. Matern Fetal Neonatal Med."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9521510","article-title":"Placental delta-like 1 gene DNA methylation levels are related to mothers\u2019 blood glucose concentration","volume":"2019","author":"Zhao","year":"2019","journal-title":"J. Diabetes Res."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-s225","article-title":"Summary and recommendations of the fifth international workshop-conference on gestational diabetes mellitus","volume":"30","author":"Metzger","year":"2007","journal-title":"Diabetes Care"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/11.19.6883","article-title":"The 5-methylcytosine content of DNA from human tumors","volume":"11","author":"Gama-Sosa","year":"1983","journal-title":"Nucleic Acids Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/biology5010003","article-title":"DNA Methylation analysis: choosing the right method","volume":"5","author":"Kurdyukov","year":"2016","journal-title":"Biol. (Basel)"},{"key":"B62","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13148-017-0311-0","article-title":"What\u2019s in a name? Context-dependent significance of \u2018global\u2019 methylation measures in human health and disease","volume":"9","author":"Vryer","year":"2017","journal-title":"Clin. Epigenetics"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.01.013","article-title":"Adipokine levels during the first or early second trimester of pregnancy and subsequent risk of gestational diabetes mellitus: a systematic review","volume":"64","author":"Bao","year":"2015","journal-title":"Metabolism."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0264-x","article-title":"Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism","volume":"49","author":"Catalano","year":"2006","journal-title":"Diabetologia."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025103319328","article-title":"DNA Methylation analysis techniques","author":"Dahl","year":"2003","journal-title":"Biogerontology."},{"key":"B66","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s12020-009-9278-8","article-title":"Adiponectin action from head to toe","volume":"37","author":"Brochu-Gaudreau","year":"2010","journal-title":"Endocrine."},{"key":"B67","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.metabol.2017.08.003","article-title":"Maternal circulating adipokine profile and insulin resistance in women at high risk of developing gestational diabetes mellitus","volume":"75","author":"Guelfi","year":"2017","journal-title":"Metab. Clin. Exp."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.1166","article-title":"Hypoxia-inducible factor-3alpha functions as an accelerator of 3T3-L1 adipose differentiation","volume":"32","author":"Hatanaka","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/35107085","article-title":"Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression","volume":"414","author":"Makino","year":"2001","journal-title":"Nature."},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathophys.2012.06.002","article-title":"HIF-3\u03b1 mRNA expression changes in different tissues and their role in adaptation to intermittent hypoxia and physical exercise","volume":"19","author":"Drevytska","year":"2012","journal-title":"Pathophysiology."},{"key":"B71","doi-asserted-by":"publisher","first-page":"27969","DOI":"10.1038\/srep27969","article-title":"Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction","volume":"6","author":"Pfeiffer","year":"2016","journal-title":"Sci. Rep."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12316","article-title":"Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q10 on inflammatory activity","volume":"177","author":"Brauner","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"71","DOI":"10.20471\/acc.2018.57.01.08","article-title":"Association between interleukin-10 gene (-1082g\/A) polymorphism and type 2 diabetes, diabetes-related traits, and microvascular complications in the Croatian population","volume":"57","author":"Canecki-Var\u017ei\u0107","year":"2018","journal-title":"Acta Clin. Croat"},{"key":"B74","doi-asserted-by":"publisher","first-page":"976810","DOI":"10.1155\/2016\/7965317","article-title":"Analysis of inflammatory mediators in type 2 diabetes patients","volume":"2013","author":"Al-Shukaili","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0980","article-title":"Modulation of adipokines and cytokines in gestational diabetes and macrosomia","volume":"91","author":"At\u00e8gbo","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.4.1088","article-title":"Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: The Leiden 85-plus study","volume":"51","author":"van Exel","year":"2002","journal-title":"Diabetes."},{"key":"B77","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.diabres.2007.12.012","article-title":"Adipokines and insulin resistance during pregnancy","volume":"80","author":"Zavalza-G\u00f3mez","year":"2008","journal-title":"Diabetes Res. Clin. Practice"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod63.5.1219","article-title":"Leptin in pregnancy","volume":"63","author":"Henson","year":"2000","journal-title":"Biol. Reproduction"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12271","article-title":"Leptin and leptin receptor polymorphisms, plasma leptin levels and obesity in Tunisian volunteers","volume":"99","author":"Nesrine","year":"2018","journal-title":"Int. J. Exp. Pathol."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/srep23948","article-title":"Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2000.00320.x","article-title":"Identification of an imprinted gene, Meg3\/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q","volume":"5","author":"Miyoshi","year":"2000","journal-title":"Genes Cells"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.8062","article-title":"Mechanism associated with aberrant lncRNA MEG3 expression in gestational diabetes mellitus","volume":"18","author":"Zhang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0037","article-title":"Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism","volume":"27","author":"Handschin","year":"2006","journal-title":"Endocr. Rev."},{"key":"B84","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1113\/jphysiol.2007.135871","article-title":"Diabetes associated cell stress and dysfunction: Role of mitochondrial and non-mitochondrial ROS production and activity","volume":"583","author":"Newsholme","year":"2007","journal-title":"J. Physiol."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803567","article-title":"Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1\u03b1 and PPAR\u03b2\/\u03b4 gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus","volume":"31","author":"Mensink","year":"2007","journal-title":"Int. J. Obes."},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHAM.0000041444.06122.8d","article-title":"Peroxisome proliferator-activated receptor (PPAR)-alpha: a pharmacological target with a promising future","volume":"21","author":"van Raalte","year":"2004","journal-title":"Pharm. Res."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.2.1.153","article-title":"Genome organization, function, and imprinting in prader-willi and angelman syndromes","volume":"2","author":"Nicholls","year":"2001","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm225","article-title":"Inactivation of the mouse Magel2 gene results in growth abnormalities similar to prader-willi syndrome","volume":"16","author":"Bischof","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412759111","article-title":"Obesity accelerates epigenetic aging of human liver","volume":"111","author":"Horvath","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B90","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1159\/000109637","article-title":"Genomic imprinting\u2013roles and regulation in development","volume":"12","author":"Kelsey","year":"2007","journal-title":"Endocr. Dev."},{"key":"B91","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/(SICI)1096-8628(19961202)66:1<77::AID-AJMG18>3.0.CO;2-N","article-title":"Validation studies of SNRPN methylation as a diagnostic test for prader-willi syndrome","volume":"66","author":"Kubota","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmr047","article-title":"Assisted reproduction treatment and epigenetic inheritance","volume":"18","author":"van Montfoort","year":"2012","journal-title":"Hum. Reprod. Update"},{"key":"B93","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12881-015-0174-1","article-title":"Leptin and adiponectin DNA methylation levels in adipose tissues and blood cells are associated with BMI, waist girth and LDL-cholesterol levels in severely obese men and women","volume":"16","author":"Houde","year":"2015","journal-title":"BMC Med. Genet."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.2217\/epi.09.14","article-title":"Genome-wide DNA methylation profiling using infinium\u00ae assay","volume":"1","author":"Bibikova","year":"2009","journal-title":"Future Med. Ltd London UK"},{"key":"B95","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ymeth.2020.10.002","article-title":"DNA Methylation methods: Global DNA methylation and methylomic analyses","volume":"187","author":"Li","year":"2021","journal-title":"Methods."},{"key":"B96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-31143-2_89-1","article-title":"Illumina HumanMethylation BeadChip for genome-wide DNA methylation profiling: advantages and limitations","volume-title":"Handbook of nutrition, diet, and epigenetics","author":"Nakabayashi","year":"2017"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190698","article-title":"Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy","volume":"13","author":"Alexander","year":"2018","journal-title":"PLoS One"},{"key":"B98","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13148-019-0687-0","article-title":"Early-life determinants of hypoxia-inducible factor 3A gene (HIF3\u03b1) methylation: A birth cohort study","volume":"11","author":"Mansell","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.11.027","article-title":"Non-hypoxic induction of HIF-3\u03b1 by 2-deoxy-D-glucose and insulin","volume":"352","author":"Heidbreder","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62674-4","article-title":"DNA Methylation and body-mass index: A genome-wide analysis","volume":"383","author":"Dick","year":"2014","journal-title":"Lancet"},{"key":"B101","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13148-016-0258-6","article-title":"DNA Methylation and gene expression of HIF3\u03b1: cross-tissue validation and associations with BMI and insulin resistance","volume":"8","author":"Main","year":"2016","journal-title":"Clin. Epigenet"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.2217\/epi.15.45","article-title":"HIF3\u03b1 association with adiposity: The story begins before birth","volume":"7","author":"Pan","year":"2015","journal-title":"Future Med. Ltd London UK"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.113.01449","article-title":"Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats","volume":"62","author":"Zhou","year":"2013","journal-title":"Hypertension"},{"key":"B104","doi-asserted-by":"publisher","first-page":"897S","DOI":"10.3945\/ajcn.110.001933","article-title":"DNA Methylation in metabolic disorders","volume":"93","author":"Barres","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0916-5","article-title":"Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion","volume":"51","author":"Ling","year":"2008","journal-title":"Diabetologia."},{"key":"B106","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-420194-1.00017-8","article-title":"Chapter 11 - DNA methylation in metabolic diseases","volume-title":"DNA Methylation and complex human disease","author":"Neidhart","year":"2016"},{"key":"B107","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12958-017-0244-7","article-title":"Mitochondrial content, oxidative, and nitrosative stress in human full-term placentas with gestational diabetes mellitus","volume":"15","author":"Ram\u00edrez-Emiliano","year":"2017","journal-title":"Reprod. Biol. Endocrinol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2413","article-title":"Deoxyribonucleic acid methylation and gene expression of PPARGC1A in human muscle is influenced by high-fat overfeeding in a birth-weight-dependent manner","volume":"95","author":"Br\u00f8ns","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B109","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3390\/jcm8010087","article-title":"Altered adipose tissue DNA methylation status in metabolic syndrome: Relationships between global DNA methylation and specific methylation at adipogenic, lipid metabolism and inflammatory candidate genes and metabolic variables","volume":"8","author":"Castellano-Castillo","year":"2019","journal-title":"J. Clin. Med."},{"key":"B110","doi-asserted-by":"publisher","first-page":"108951","DOI":"10.1016\/j.jnutbio.2022.108951","article-title":"Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the ppar\u03b1 promoter region","volume":"103","author":"Ando","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16551","article-title":"Gestational high-fat diet impaired demethylation of ppar\u03b1 and induced obesity of offspring","volume":"25","author":"Pang","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12263-014-0452-0","article-title":"PPAR\u03b1 via HNF4\u03b1 regulates the expression of genes encoding hepatic amino acid catabolizing enzymes to maintain metabolic homeostasis","volume":"10","author":"Contreras","year":"2015","journal-title":"Genes Nutr."},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060750","article-title":"DNA Isolation method is a source of global DNA methylation variability measured with LUMA. Experimental analysis and a systematic review","volume":"8","author":"Soriano-T\u00e1rraga","year":"2013","journal-title":"PLoS One"},{"key":"B114","doi-asserted-by":"publisher","first-page":"3417","DOI":"10.1038\/s41467-019-11052-9","article-title":"Cell-type-specific resolution epigenetics without the need for cell sorting or single-cell biology","volume":"10","author":"Rahmani","year":"2019","journal-title":"Nat. Commun."},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079044","article-title":"Comparison of methods for quantification of global DNA methylation in human cells and tissues","volume":"8","author":"Lisanti","year":"2013","journal-title":"PLoS One"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041361","article-title":"Differential DNA methylation in purified human blood cells: Implications for cell lineage and studies on disease susceptibility","volume":"7","author":"Reinius","year":"2012","journal-title":"PLoS One"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-017-0400-0","article-title":"Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver","volume":"9","author":"Garc\u00eda-Calz\u00f3n","year":"2017","journal-title":"Clin. Epigenet."},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1205412","article-title":"450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy","volume":"120","author":"Joubert","year":"2012","journal-title":"Environ. Health Perspect."},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-612-8_23","article-title":"Dietary and lifestyle factors of DNA methylation","volume":"863","author":"Lim","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"5654","DOI":"10.1038\/s41598-018-23772-x","article-title":"Association between DNA methylation in cord blood and maternal smoking: The Hokkaido study on environment and children\u2019s health","volume":"8","author":"Miyake","year":"2018","journal-title":"Sci. Rep."},{"key":"B121","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15592294.2016.1257450","article-title":"Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation","volume":"12","author":"Pauwels","year":"2017","journal-title":"Epigenetics."},{"key":"B122","doi-asserted-by":"publisher","first-page":"7843","DOI":"10.3390\/ijerph17217843","article-title":"Intimate partner violence: A risk factor for gestational diabetes","volume":"17","author":"Pheiffer","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.04.023","article-title":"Decoding the organization, dynamics, and function of the 4D genome","volume":"56","author":"Aboelnour","year":"2021","journal-title":"Dev. Cell."}],"container-title":["Frontiers in Clinical Diabetes and Healthcare"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcdhc.2022.982665\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T07:39:56Z","timestamp":1663832396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcdhc.2022.982665\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":123,"alternative-id":["10.3389\/fcdhc.2022.982665"],"URL":"https:\/\/doi.org\/10.3389\/fcdhc.2022.982665","relation":{},"ISSN":["2673-6616"],"issn-type":[{"value":"2673-6616","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]},"article-number":"982665"}}