{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:04:27Z","timestamp":1775174667479,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The etiology of women with gestational diabetes mellitus (GDM) and a greater risk of developing type 2 diabetes (T2D) after delivery remains unknown. This study aimed to investigate the global gene expression in four postpartum women with previous GDM (pGDM), three with T2D, and three with a history of normoglycemic pregnancy (controls). Total RNA was extracted from whole blood between March and May 2020. Global mRNA expression was determined using an Affymetrix Human Gene 2.0 ST Array. The expression of the selected focused genes was validated by RT-PCR. The microarray revealed 140 transcripts (p &lt; 0.05, fold change cut-off \u2265 2) in patients with pGDM compared to controls. We identified 583 gene-altered transcripts between patients with T2D and controls. Interestingly, 60 transcripts had genes shared by pGDM or T2D versus the controls. The selected upregulated genes involved in inflammatory response, glycosylation, and death-like domains, according to the functional network analysis of pGDM (TNFAIP6, PDK3) and T2D (MMP9 and CARD6), showed similar trends to those obtained via microarray. Thus, these differentially expressed genes and their corresponding network and pathway analyses in women with pGDM and T2D offer valuable insights into the possible biological mechanisms of the progression of GDM to T2D.<\/jats:p>","DOI":"10.3390\/life15081270","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:02:09Z","timestamp":1754910129000},"page":"1270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microarray Analysis of Differentially Expressed Genes in Peripheral Blood of Postpartum Women with Gestational Diabetes Mellitus and Type 2 Diabetes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1194-8545","authenticated-orcid":false,"given":"Samar","family":"Sultan","sequence":"first","affiliation":[{"name":"Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Regenerative Medicine Unit, King Fahad Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"M\u0142ynarska, E., Czarnik, W., Dzie\u017ca, N., J\u0119draszak, W., Majchrowicz, G., Prusinowski, F., Stabrawa, M., Rysz, J., and Franczyk, B. (2025). Type 2 diabetes mellitus: New pathogenetic mechanisms, treatment and the most important complications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031094"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2337\/dc24-1199","article-title":"Association between glycemia, glycemic variability, and pregnancy complications in early GDM","volume":"48","author":"Immanuel","year":"2025","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12967-023-04005-w","article-title":"Lactation duration and lifetime progression to metabolic syndrome in women according to their history of gestational diabetes: A prospective longitudinal community-based cohort study","volume":"21","author":"Farahmand","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(09)60731-5","article-title":"Type 2 diabetes mellitus after gestational diabetes: A systematic review and meta-analysis","volume":"373","author":"Bellamy","year":"2009","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e000490","DOI":"10.1161\/JAHA.113.000490","article-title":"History of gestational diabetes mellitus and future risk of atherosclerosis in mid-life: The coronary artery risk development in young adults study","volume":"3","author":"Gunderson","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00125-016-3927-2","article-title":"Quantification of the type 2 diabetes risk in women with gestational diabetes: A systematic review and meta-analysis of 95,750 women","volume":"59","author":"Rayanagoudar","year":"2016","journal-title":"Diabetologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.amjmed.2008.09.034","article-title":"Risk factors for type 2 diabetes among women with gestational diabetes: A systematic review","volume":"122","author":"Barone","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12933-014-0138-3","article-title":"Biomarkers of endothelial dysfunction in relation to impaired carbohydrate metabolism following pregnancy with gestational diabetes mellitus","volume":"13","author":"Bozkurt","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"458610","DOI":"10.1155\/2012\/458610","article-title":"Previous gestational diabetes mellitus and markers of cardiovascular risk","volume":"2012","author":"Vrachnis","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155695","DOI":"10.1016\/j.metabol.2023.155695","article-title":"Postpartum defects in inflammatory response after gestational diabetes precede progression to type 2 diabetes: A nested case-control study within the SWIFT study","volume":"149","author":"Van","year":"2023","journal-title":"Metabolism"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1080\/01443615.2018.1467389","article-title":"Screening for gestational diabetes mellitus: A Caribbean perspective","volume":"38","author":"Bassaw","year":"2018","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1210\/jcem.86.3.7339","article-title":"Pancreatic B-cell defects in gestational diabetes: Implications for the pathogenesis and prevention of type 2 diabetes","volume":"86","author":"Buchanan","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","first-page":"955","article-title":"Familial aggregation of type 2 diabetes and chronic hypertension in women with gestational diabetes mellitus","volume":"48","author":"Williams","year":"2003","journal-title":"J. Reprod. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1515\/hmbci-2016-0022","article-title":"Hyperglycemic memory in metabolism and cancer","volume":"26","author":"Lee","year":"2016","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, Z., Zhao, H., Guan, W., Kang, X., Tai, X., and Shen, Y. (2018). Metabolic memory in mitochondrial oxidative damage triggers diabetic retinopathy. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0921-0"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1161\/CIRCRESAHA.116.306819","article-title":"Epigenetic changes in diabetes and cardiovascular risk","volume":"118","author":"Keating","year":"2016","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/2211-5463.12370","article-title":"The postpartum effect of maternal diabetes on the circulating levels of sirtuins and superoxide dismutase","volume":"8","author":"Sultan","year":"2018","journal-title":"FEBS Open Bio."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e98","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: Response to Weinert","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST\u00a9) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhao, M., Yao, Z., Zhang, Y., Ma, L., Pang, W., Ma, S., Xu, Y., and Wei, L. (2025). Predictive value of machine learning for the progression of gestational diabetes mellitus to type 2 diabetes: A systematic review and meta-analysis. BMC Med. Inform. Decis. Mak., 25.","DOI":"10.1186\/s12911-024-02848-x"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, F., Zhao, Y., Xing, J., and Gong, L. (2025). Avicularin as a Promising Therapeutic Agent for Gestational Diabetes Mellitus: Modulation of Inflammatory, Oxidative Stress, and Apoptotic Pathways. Doklady Biochemistry and Biophysics, Springer.","DOI":"10.1134\/S1607672924601471"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Elguoshy, A., Yamamoto, K., Hirao, Y., Yanagita, K., Uchimoto, T., Kamimura, T., Takazawa, T., and Yamamoto, T. (2025). Machine Learning-Driven Glycoproteomic Profiling Identifies Novel Diabetes-Associated Glycosylation Biomarkers. medRxiv.","DOI":"10.1101\/2025.02.24.25322514"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, H., Yao, Q., Wang, X., Xie, H., Yang, C., Gao, H., and Xie, C. (2024). The research progress of crosstalk mechanism of autophagy and apoptosis in diabetic vascular endothelial injury. Biomed. Pharmacother., 170.","DOI":"10.1016\/j.biopha.2023.116072"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2303584","DOI":"10.1002\/advs.202303584","article-title":"Scutellarin rescued mitochondrial damage through ameliorating mitochondrial glucose oxidation via the Pdk-Pdc axis","volume":"10","author":"Sheng","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-7075-11-10","article-title":"The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility","volume":"11","author":"Zhang","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/s41419-023-06249-2","article-title":"Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes","volume":"14","author":"Yao","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41419-024-06430-1","article-title":"Glucocorticoid activates STAT3 and NF-\u03baB synergistically with inflammatory cytokines to enhance the anti-inflammatory factor TSG6 expression in mesenchymal stem\/stromal cells","volume":"15","author":"Huang","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12627","DOI":"10.1074\/jbc.M116.720953","article-title":"The anti-inflammatory protein TSG-6 regulates chemokine function by inhibiting chemokine\/glycosaminoglycan interactions","volume":"291","author":"Dyer","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20503121211026832","DOI":"10.1177\/20503121211026832","article-title":"Aberrant expression of proatherogenic cytokines and growth factors in human umbilical vein endothelial cells from newborns of type 2 diabetic women","volume":"9","author":"Sultan","year":"2021","journal-title":"SAGE Open Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1002\/jcp.24993","article-title":"The role of maternal gestational diabetes in inducing fetal endothelial dysfunction","volume":"230","author":"Sultan","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1210\/jc.2004-2494","article-title":"Subclinical inflammation and vascular dysfunction in women with previous gestational diabetes mellitus","volume":"90","author":"Heitritter","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1056\/NEJM200003233421202","article-title":"C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women","volume":"342","author":"Ridker","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1161\/01.CIR.102.1.42","article-title":"Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS)","volume":"102","author":"Festa","year":"2000","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bai, C., Yang, W., Qi, G., Yang, L., Wu, Q., Peng, J., Wang, N., and Liu, T. (2025). Causal association between matrix metalloproteinases and diabetic neuropathy: A two-sample Mendelian randomization study. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1429121"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8298","DOI":"10.1039\/D5TB00625B","article-title":"Matrix metalloproteinase-triggered self-assembling peptides for biomedical applications","volume":"13","author":"Liu","year":"2025","journal-title":"J. Mater. Chem. B."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tanase, D.M., Valasciuc, E., Anton, I.B., Gosav, E.M., Dima, N., Cucu, A.I., Costea, C.F., Floria, D.E., Hurjui, L.L., and Tarniceriu, C.C. (2025). Matrix Metalloproteinases: Pathophysiologic Implications and Potential Therapeutic Targets in Cardiovascular Disease. Biomolecules, 15.","DOI":"10.3390\/biom15040598"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, B., Su, L., Loo, S.J., Gao, Y., Khin, E., Kong, X., Dalan, R., Su, X., Lee, K.O., and Ma, J. (2024). Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1369369"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.carpath.2017.05.003","article-title":"Exercise training ameliorates matrix metalloproteinases 2 and 9 messenger RNA expression and mitigates adverse left ventricular remodeling in streptozotocin-induced diabetic rats","volume":"29","author":"Silva","year":"2017","journal-title":"Cardiovasc. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0021-9150(03)00140-0","article-title":"High glucose alters matrix metalloproteinase expression in two key vascular cells: Potential impact on atherosclerosis in diabetes","volume":"168","author":"Death","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1071\/RD00078","article-title":"Membrane-type matrix metalloproteinase-9 activity in placental tissue from patients with pre-existing and gestational diabetes mellitus","volume":"12","author":"Pustovrh","year":"2000","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1073\/pnas.0510380103","article-title":"Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-\u03baB activation","volume":"103","author":"Dufner","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1177\/153537020122600207","article-title":"Dietary zinc supplementation inhibits NF\u03baB activation and protects against chemically induced diabetes in CD1 mice","volume":"226","author":"Ho","year":"2001","journal-title":"Exp. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109690","DOI":"10.1016\/j.exer.2023.109690","article-title":"Circ-CARD6 inhibits oxidative stress-induced apoptosis and autophagy in ARPE-19 cells via the miR-29b-3p\/PRDX6\/PI3K\/Akt axis","volume":"238","author":"Fan","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.brainresbull.2009.05.006","article-title":"Metabolic memory in diabetes\u2013from in vitro oddity to in vivo problem: Role of Apoptosis","volume":"81","author":"Kowluru","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1053\/j.ajkd.2003.12.028","article-title":"Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy","volume":"43","author":"Baelde","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2147\/DMSO.S334144","article-title":"Genome-Wide Transcriptome Analysis in Type 2 Diabetes Patients Treated by Sitagliptin","volume":"15","author":"Ma","year":"2022","journal-title":"Diabetes Metab. Syndr. Obes."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/8\/1270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:24:40Z","timestamp":1760034280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/8\/1270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["life15081270"],"URL":"https:\/\/doi.org\/10.3390\/life15081270","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}