{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:53:32Z","timestamp":1792173212950,"version":"4.4.0"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015223","name":"Danish Diabetes Academy","doi-asserted-by":"publisher","award":["NNF17SA0031406"],"award-info":[{"award-number":["NNF17SA0031406"]}],"id":[{"id":"10.13039\/100015223","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Community\u2019s 7th Framework Program","award":["242187"],"award-info":[{"award-number":["242187"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter \u2018Vitamin D and lifestyle intervention for GDM prevention (DALI)\u2019 trial using serum samples from obese pregnant women (BMI \u2265 29 kg\/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (&lt;20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.<\/jats:p>","DOI":"10.3390\/cells10010170","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T05:17:34Z","timestamp":1610947054000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7557-5376","authenticated-orcid":false,"given":"Anja","family":"S\u00f8rensen","sequence":"first","affiliation":[{"name":"Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5694-4324","authenticated-orcid":false,"given":"Mireille","family":"van Poppel","sequence":"additional","affiliation":[{"name":"Institute of Human Movement Science, Sport and Health, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-3230","authenticated-orcid":false,"given":"Gernot","family":"Desoye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medizinische Universitaet Graz, 8036 Graz, Austria"},{"name":"Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2067-5246","authenticated-orcid":false,"given":"Peter","family":"Damm","sequence":"additional","affiliation":[{"name":"Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-0761","authenticated-orcid":false,"given":"David","family":"Simmons","sequence":"additional","affiliation":[{"name":"Macarthur Clinical School, Western Sydney University, Sydney 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorte","family":"Jensen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Odense, Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3598-2775","authenticated-orcid":false,"given":"Louise","family":"Dalgaard","sequence":"additional","affiliation":[{"name":"Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The DALI Core Investigator Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.2337\/diacare.26.7.2005","article-title":"Population Health Significance of Gestational Diabetes","volume":"26","author":"Cheung","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2337\/dc07-1596","article-title":"High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: The role of intrauterine hyperglycemia","volume":"31","author":"Clausen","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1464-5491.2006.01840.x","article-title":"Glucose tolerance of offspring of mother with gestational diabetes mellitus in a low-risk population","volume":"23","author":"Malcolm","year":"2006","journal-title":"Diabet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.2337\/dc10-0139","article-title":"Prevalence and predictors of overweight and insulin resistance in offspring of mothers with gestational diabetes mellitus","volume":"33","author":"Boerschmann","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"(2015). American Diabetes Association Standards of Medical Care in Diabetes\u20142015 Abridged for Primary Care Providers. Clin. Diabetes, 33, 97\u2013111.","DOI":"10.2337\/diaclin.33.2.97"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"676","DOI":"10.2337\/dc10-0719","article-title":"International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_7","unstructured":"National Institutes of Health (2013, January 4\u20136). Diagnosing gestational diabetes mellitus. Proceedings of the NIH Consensus Development Conference Statement, Bethesda, MD, USA."},{"key":"ref_8","unstructured":"World Health Organization Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy, WHO."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41572-019-0098-8","article-title":"Gestational diabetes mellitus","volume":"5","author":"McIntyre","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s40618-017-0791-y","article-title":"Impact of risk factors for gestational diabetes (GDM) on pregnancy outcomes in women with GDM","volume":"41","author":"Filardi","year":"2018","journal-title":"J. Endocrinol. Invest."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"982","DOI":"10.2337\/dc16-0160","article-title":"Accelerated Fetal Growth Prior to Diagnosis of Gestational Diabetes Mellitus: A Prospective Cohort Study of Nulliparous Women","volume":"39","author":"Sovio","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2337\/dc15-1887","article-title":"Issues with the Diagnosis and Classification of Hyperglycemia in Early Pregnancy","volume":"39","author":"McIntyre","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.diabres.2018.06.001","article-title":"Perspectives on diagnostic strategies for hyperglycaemia in pregnancy\u2014Dealing with the barriers and challenges: Europe","volume":"145","author":"Egan","year":"2018","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Immanuel, J., and Simmons, D. (2017). Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis. Curr. Diab. Rep.","DOI":"10.1007\/s11892-017-0943-7"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Filardi, T., Catanzaro, G., Mardente, S., Zicari, A., Santangelo, C., Lenzi, A., Morano, S., and Ferretti, E. (2020). Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114020"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/cr.2008.282","article-title":"Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases","volume":"18","author":"Chen","year":"2008","journal-title":"Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gallo, A., Tandon, M., Alevizos, I., and Illei, G.G. (2012). The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030679"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiong, D.D., Lv, J., Wei, K.L., Feng, Z.B., Chen, J.T., Liu, K.C., Chen, G., and Luo, D.Z. (2017). A nine-miRNA signature as a potential diagnostic marker for breast carcinoma: An integrated study of 1,110 cases. Oncol. Rep.","DOI":"10.3892\/or.2017.5600"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"T\u00fcfekci, K.U., \u00d6ner, M.G., Meuwissen, R.L.J., and Gen\u00e7, \u015e. (2014). The role of microRNAs in human diseases. Methods Mol. Biol.","DOI":"10.1007\/978-1-62703-748-8_3"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Paul, P., Chakraborty, A., Sarkar, D., Langthasa, M., Rahman, M., Bari, M., Singha, R.K.S., Malakar, A.K., and Chakraborty, S. (2018). Interplay between miRNAs and human diseases. J. Cell. Physiol.","DOI":"10.1002\/jcp.25854"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liang, Y., Ridzon, D., Wong, L., and Chen, C. (2007). Characterization of microRNA expression profiles in normal human tissues. Bmc Genom., 8.","DOI":"10.1186\/1471-2164-8-166"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.placenta.2012.05.009","article-title":"MicroRNA expression profiles of trophoblastic cells","volume":"33","author":"Chaiwangyen","year":"2012","journal-title":"Placenta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2020.00169","article-title":"The miRNA-29b Is Downregulated in Placenta During Gestational Diabetes Mellitus and May Alter Placenta Development by Regulating Trophoblast Migration and Invasion Through a HIF3A-Dependent Mechanism","volume":"11","author":"Sun","year":"2020","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/biof.1461","article-title":"microRNA-96 protects pancreatic \u03b2-cell function by targeting PAK1 in gestational diabetes mellitus","volume":"44","author":"Li","year":"2018","journal-title":"BioFactors"},{"key":"ref_26","first-page":"1","article-title":"Up-regulation of miR-98 and unraveling regulatory mechanisms in gestational diabetes mellitus","volume":"6","author":"Cao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1042\/CS20180825","article-title":"Gestational diabetes alters microRNA signatures in human feto-placental endothelial cells depending on fetal sex","volume":"132","author":"Strutz","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.1210\/jc.2018-02693","article-title":"miRNA Profiles in Extracellular Vesicles From Serum Early in Pregnancies Complicated by Gestational Diabetes Mellitus","volume":"104","author":"Gillet","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s13353-011-0055-z","article-title":"Microarray analysis of differentially expressed microRNAs in non-regressed and regressed bovine corpus luteum tissue; microRNA-378 may suppress luteal cell apoptosis by targeting the interferon gamma receptor 1 gene","volume":"52","author":"Ma","year":"2011","journal-title":"J. Appl. Genet."},{"key":"ref_30","first-page":"156","article-title":"MEG3 damages fetal endothelial function induced by gestational diabetes mellitus via AKT pathway","volume":"9","author":"Martino","year":"2019","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hocaoglu, M., Demirer, S., Loclar Karaalp, I., Kaynak, E., Attar, E., Turgut, A., Karateke, A., and Komurcu-Bayrak, E. (2020). Identification of miR-16-5p and miR-155-5p microRNAs differentially expressed in circulating leukocytes of pregnant women with polycystic ovary syndrome and gestational diabetes. Gynecol. Endocrinol., 1\u20135.","DOI":"10.1080\/09513590.2020.1843620"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.preghy.2019.04.004","article-title":"Differential expression of candidate circulating microRNAs in maternal blood leukocytes of the patients with preeclampsia and gestational diabetes mellitus","volume":"17","author":"Hocaoglu","year":"2019","journal-title":"Pregnancy Hypertens."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhao, C., Dong, J., Jiang, T., Shi, Z., Yu, B., Zhu, Y., Chen, D., Xu, J., Huo, R., and Dai, J. (2011). Early second-trimester serum miRNA profiling predicts gestational diabetes mellitus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023925"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Ibarra, A., Mart\u00ednez-Razo, L.D., V\u00e1zquez-Mart\u00ednez, E.R., Mart\u00ednez-Cruz, N., Flores-Ram\u00edrez, R., Garc\u00eda-G\u00f3mez, E., L\u00f3pez-L\u00f3pez, M., Ortega-Gonz\u00e1lez, C., Camacho-Arroyo, I., and Cerb\u00f3n, M. (2019). Unhealthy levels of phthalates and bisphenol a in mexican pregnant women with gestational diabetes and its association to altered expression of miRNAs involved with metabolic disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133343"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1530\/EJE-19-0206","article-title":"Early diagnosis of gestational diabetes mellitus using circulating microRNAs","volume":"181","author":"Yoffe","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E1446","DOI":"10.1210\/jc.2015-2872","article-title":"Altered Circulating miRNA Expression Profile in Pregestational and Gestational Obesity","volume":"100","author":"Ortega","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Xue, Y., Lv, J., Xu, P., Gu, L., Cao, J., Xu, L., Xue, K., and Li, Q. (2017). Identification of microRNAs and genes associated with hyperandrogenism in the follicular fluid of women with polycystic ovary syndrome. J. Cell. Biochem., 3913\u20133921.","DOI":"10.1002\/jcb.26531"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diabres.2017.07.024","article-title":"Circulating early- and mid-pregnancy microRNAs and risk of gestational diabetes","volume":"132","author":"Wander","year":"2017","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2017.00345","article-title":"Circulating microRNA (miRNA) expression profiling in plasma of patients with gestational diabetes mellitus reveals upregulation of miRNA miR-330-3p","volume":"8","author":"Sebastiani","year":"2017","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neures.2017.08.003","article-title":"Central nervous system development-related microRNAs levels increase in the serum of gestational diabetic women during the first trimester of pregnancy","volume":"130","author":"Perichart","year":"2018","journal-title":"Neurosci. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1042\/CS20180487","article-title":"Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity","volume":"132","author":"Nair","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s40291-018-0325-0","article-title":"Decreased Expression of Circulating miR-20a-5p in South African Women with Gestational Diabetes Mellitus","volume":"22","author":"Pheiffer","year":"2018","journal-title":"Mol. Diagn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.gene.2018.06.004","article-title":"MicroRNA profiling of second trimester maternal plasma shows upregulation of miR-195-5p in patients with gestational diabetes","volume":"672","author":"Tagoma","year":"2018","journal-title":"Gene"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jelsma, J.G.M., van Poppel, M.N.M., Galjaard, S., Desoye, G., Corcoy, R., Devlieger, R., van Assche, A., Timmerman, D., Jans, G., and Harreiter, J. (2013). DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: An European multicentre, randomised trial\u2014study protocol. Bmc Pregnancy Childbirth, 13.","DOI":"10.1186\/1471-2393-13-142"},{"key":"ref_45","first-page":"903","article-title":"Effect of Physical Activity and\/or Healthy Eating on GDM Risk: The DALI Lifestyle Study","volume":"102","author":"Simmons","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Corcoy, R., Mendoza, L.C., Simmons, D., Desoye, G., Adelantado, J.M., Chico, A., Devlieger, R., van Assche, A., Galjaard, S., and Timmerman, D. (2020). The DALI vitamin D randomized controlled trial for gestational diabetes mellitus prevention: No major benefit shown besides vitamin D sufficiency. Clin. Nutr., 39.","DOI":"10.1016\/j.clnu.2019.04.006"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., and Turner, R.C. (1985). Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia.","DOI":"10.1007\/BF00280883"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Katz, A., Nambi, S.S., Mather, K., Baron, A.D., Follmann, D.A., Sullivan, G., and Quon, M.J. (2000). Quantitative insulin sensitivity check index: A simple, accurate method for assessing insulin sensitivity in humans. J. Clin. Endocrinol. Metab.","DOI":"10.1210\/jcem.85.7.6661"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mari, A., Pacini, G., Murphy, E., Ludvik, B., and Nolan, J.J. (2001). A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care.","DOI":"10.2337\/diacare.24.3.539"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Matsuda, M., and DeFronzo, R.A. (1999). Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care.","DOI":"10.2337\/diacare.22.9.1462"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Patarr\u00e3o, R.S., Wayne Lautt, W., and Paula Macedo, M. (2014). Assessment of methods and indexes of insulin sensitivity. Rev. Port. Endocrinol. Diabetes E Metab.","DOI":"10.1016\/j.rpedm.2013.10.004"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mi, H., Muruganujan, A., Huang, X., Ebert, D., Mills, C., Guo, X., and Thomas, P.D. (2019). Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0). Nat. Protoc.","DOI":"10.1038\/s41596-019-0128-8"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijgo.2015.01.010","article-title":"Profiling maternal plasma microRNA expression in early pregnancy to predict gestational diabetes mellitus","volume":"130","author":"Zhu","year":"2015","journal-title":"Int. J. Gynecol. Obs."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3892\/ijmm.2014.1989","article-title":"Differential expression of circulating miRNAs in maternal plasma in pregnancies with fetal macrosomia","volume":"35","author":"Ge","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/jog.13317","article-title":"Plasma microRNA-16-5p, -17-5p and -20a-5p: Novel diagnostic biomarkers for gestational diabetes mellitus","volume":"43","author":"Cao","year":"2017","journal-title":"J. Obs. Gynaecol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1158\/1940-6207.CAPR-11-0370","article-title":"Blood Cell Origin of Circulating MicroRNAs: A Cautionary Note for Cancer Biomarkers Studies","volume":"5","author":"Pritchard","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liang, Y.Z., Dong, J., Zhang, J., Wang, S., He, Y., and Yan, Y.X. (2018). Identification of neuroendocrine stress response-related circulating MicroRNAs as biomarkers for type 2 diabetes mellitus and insulin resistance. Front. Endocrinol. (Lausanne).","DOI":"10.3389\/fendo.2018.00132"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Khaliq, O.P., Murugesan, S., Moodley, J., and Mackraj, I. (2018). Differential expression of miRNAs are associated with the insulin signaling pathway in preeclampsia and gestational hypertension. Clin. Exp. Hypertens.","DOI":"10.1080\/10641963.2018.1431257"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"598","DOI":"10.2337\/db15-0966","article-title":"Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation","volume":"65","author":"Salomon","year":"2016","journal-title":"Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mattis, A.N., Song, G., Hitchner, K., Kim, R.Y., Lee, A.Y., Sharma, A.D., Malato, Y., Mcmanus, M.T., Esau, C.C., and Koller, E. (2015). A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver. Hepatology.","DOI":"10.1002\/hep.27379"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Dooley, J., Garcia-Perez, J.E., Sreenivasan, J., Schlenner, S.M., Vangoitsenhoven, R., Papadopoulou, A.S., Tian, L., Schonefeldt, S., Serneels, L., and Deroose, C. (2016). The microRNA-29 family dictates the balance between homeostatic and pathological glucose handling in diabetes and obesity. Diabetes.","DOI":"10.2337\/db15-0770"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bbrc.2012.08.082","article-title":"MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion","volume":"426","author":"Bagge","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s00125-010-1667-2","article-title":"Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes","volume":"53","author":"Herrera","year":"2010","journal-title":"Diabetologia"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Udesen, P.B., Glintborg, D., S\u00f8rensen, A.E., Svendsen, R., Nielsen, N.L.S., Wissing, M.L.M., Andersen, M.S., Englund, A.L.M., and Dalgaard, L.T. (2020). Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome. Endocr. Connect.","DOI":"10.1530\/EC-20-0195"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1701S","DOI":"10.1093\/jn\/136.6.1701S","article-title":"Sulfur amino acid metabolism in pregnancy: The impact of methionine in the maternal diet","volume":"136","author":"Rees","year":"2006","journal-title":"J. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E1438","DOI":"10.1210\/jc.2013-1210","article-title":"Hyperinsulinemia Stimulates Angiogenesis of Human Fetoplacental Endothelial Cells: A Possible Role of Insulin in Placental Hypervascularization in Diabetes Mellitus","volume":"98","author":"Lassance","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1210\/jc.2012-1212","article-title":"Fetal Insulin and IGF-II Contribute to Gestational Diabetes Mellitus (GDM)-Associated Up-Regulation of Membrane-Type Matrix Metalloproteinase 1 (MT1-MMP) in the Human Feto-Placental Endothelium","volume":"97","author":"Hiden","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ji, Y., Wu, Z., Dai, Z., Sun, K., Wang, J., and Wu, G. (2016). Nutritional epigenetics with a focus on amino acids: Implications for the development and treatment of metabolic syndrome. J. Nutr. Biochem.","DOI":"10.1016\/j.jnutbio.2015.08.003"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Freyberg, Z., and Saavedra, J.M. (2020). Trace Amines and Trace Amine-Associated Receptors: A New Frontier in Cell Signaling. Cell. Mol. Neurobiol.","DOI":"10.1007\/s10571-020-00800-x"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1073\/pnas.1214046110","article-title":"Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations","volume":"110","author":"Williams","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nature04367","article-title":"A brain-specific microRNA regulates dendritic spine development","volume":"439","author":"Schratt","year":"2006","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Wang, H.W., Su, S.H., Wang, Y.L., Chang, S.T., Liao, K.H., Lo, H.H., Chiu, Y.L., Hsieh, T.H., Huang, T.S., and Lin, C.S. (2016). MicroRNA-134 contributes to glucose-induced endothelial cell dysfunction and this effect can be reversed by far-infrared irradiation. PLoS ONE.","DOI":"10.1371\/journal.pone.0147067"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Jaskolka, D., Retnakaran, R., Zinman, B., and Kramer, C.K. (2015). Sex of the baby and risk of gestational diabetes mellitus in the mother: A systematic review and meta-analysis. Diabetologia.","DOI":"10.1007\/s00125-015-3726-1"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Luo, S., Cao, N., Tang, Y., and Gu, W. (2017). Identification of key microRNAs and genes in preeclampsia by bioinformatics analysis. PLoS ONE.","DOI":"10.1371\/journal.pone.0178549"},{"key":"ref_77","unstructured":"Zou, A.X., Chen, B., Li, Q.X., and Liang, Y.C. (2018). MiR-134 inhibits infiltration of trophoblast cells in placenta of patients with preeclampsia by decreasing ITGB1 expression. Eur. Rev. Med. Pharm. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.2337\/diabetes.51.7.2207","article-title":"TNF- Is a Predictor of Insulin Resistance in Human Pregnancy","volume":"51","author":"Kirwan","year":"2002","journal-title":"Diabetes"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lan, G., Xie, W., Li, L., Zhang, M., Liu, D., Tan, Y.L., Cheng, H.P., Gong, D., Huang, C., and Zheng, X.L. (2016). MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages. Biochem. Biophys. Res. Commun.","DOI":"10.1016\/j.bbrc.2015.10.158"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ameling, S., Kacprowski, T., Chilukoti, R.K., Malsch, C., Liebscher, V., Suhre, K., Pietzner, M., Friedrich, N., Homuth, G., and Hammer, E. (2015). Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study. Bmc Med. Genom.","DOI":"10.1186\/s12920-015-0136-7"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wang, R., Hong, J., Cao, Y., Shi, J., Gu, W., Ning, G., Zhang, Y., and Wang, W. (2015). Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults. Eur. J. Endocrinol.","DOI":"10.1530\/EJE-14-0867"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2337\/db16-0731","article-title":"Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes","volume":"66","author":"Willeit","year":"2017","journal-title":"Diabetes"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Hess, A.L., Larsen, L.H., Udesen, P.B., Sanz, Y., Larsen, T.M., and Dalgaard, L.T. (2020). Levels of Circulating miR-122 are Associated with Weight Loss and Metabolic Syndrome. Obesity.","DOI":"10.1002\/oby.22704"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"110824","DOI":"10.1016\/j.mce.2020.110824","article-title":"Proinflammation in maternal and fetal livers and circulating miR-122 dysregulation in a GDM rat model induced by intrauterine programming","volume":"510","author":"Fornes","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Harreiter, J., Desoye, G., van Poppel, M.N.M., Kautzky-Willer, A., Dunne, F., Corcoy, R., Devlieger, R., Simmons, D., Adelantado, J.M., and Damm, P. (2019). The Effects of Lifestyle and\/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have We Learned from the DALI Studies?. Curr. Diab. Rep., 19.","DOI":"10.1007\/s11892-019-1282-7"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.2337\/dc16-0200","article-title":"IADPSG and WHO 2013 Gestational Diabetes Mellitus Criteria Identify Obese Women With Marked Insulin Resistance in Early Pregnancy","volume":"39","author":"Harreiter","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s00592-018-1224-x","article-title":"Heterogeneity of gestational diabetes (GDM) and challenges in developing a GDM risk score","volume":"55","author":"Huvinen","year":"2018","journal-title":"Acta Diabetol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.2337\/dbi20-0004","article-title":"Defining Heterogeneity Among Women With Gestational Diabetes Mellitus","volume":"69","author":"Powe","year":"2020","journal-title":"Diabetes"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e1033","DOI":"10.1210\/clinem\/dgaa087","article-title":"Plasma Glycated CD59 Predicts Early Gestational Diabetes and Large for Gestational Age Newborns","volume":"105","author":"Ma","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"108378","DOI":"10.1016\/j.diabres.2020.108378","article-title":"Performance of early pregnancy HbA1c for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women","volume":"168","author":"Immanuel","year":"2020","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1530\/EJE-18-0003","article-title":"Risk factors for hyperglycemia in pregnancy in the DALI study differ by period of pregnancy and OGTT time point","volume":"179","author":"Mendoza","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"van Hoorn, F., Koster, M.P.H., Naaktgeboren, C.A., Groenendaal, F., Kwee, A., Lamain-de Ruiter, M., Franx, A., and Bekker, M.N. (2020). Prognostic models versus single risk factor approach in first-trimester selective screening for gestational diabetes mellitus: A prospective population-based multicentre cohort study. Bjog An. Int. J. Obs. 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