{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:39:45Z","timestamp":1793903985918,"version":"4.8.0"},"reference-count":108,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology\/MCTES","award":["2020.07020.BD"],"award-info":[{"award-number":["2020.07020.BD"]}]},{"name":"FCT","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}]},{"name":"FCT","award":["UIDP\/00709\/2020"],"award-info":[{"award-number":["UIDP\/00709\/2020"]}]},{"name":"FCT","award":["2020.07020.BD"],"award-info":[{"award-number":["2020.07020.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Since the beginning of their production, in the 1930s, phthalates have been widely used in the plastics industry to provide durability and elasticity to polymers that would otherwise be rigid, or as solvents in hygiene and cosmetic products. Taking into account their wide range of applications, it is easy to understand why their use has been increasing over the years, making them ubiquitous in the environment. This way, all living organisms are easily exposed to these compounds, which have already been classified as endocrine disruptor compounds (EDC), affecting hormone homeostasis. Along with this increase in phthalate-containing products, the incidence of several metabolic diseases has also been rising, namely diabetes. That said, and considering that factors such as obesity and genetics are not enough to explain this substantial increase, it has been proposed that the exposure to environmental contaminants may also be a risk factor for diabetes. Thus, the aim of this work is to review whether there is an association between the exposure to phthalates and the development of the several forms of diabetes mellitus, during pregnancy, childhood, and adulthood.<\/jats:p>","DOI":"10.3390\/metabo13060746","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T02:28:42Z","timestamp":1686536922000},"page":"746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["The Relationship between Phthalates and Diabetes: A Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1875-0144","authenticated-orcid":false,"given":"Melissa","family":"Mariana","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique s\/n, 6200-506 Covilh\u00e3, Portugal"},{"name":"FCS-UBI\u2014Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-5701","authenticated-orcid":false,"given":"Elisa","family":"Cairrao","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique s\/n, 6200-506 Covilh\u00e3, Portugal"},{"name":"FCS-UBI\u2014Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.envint.2016.07.004","article-title":"The effects of phthalates in the cardiovascular and reproductive systems: A review","volume":"94","author":"Mariana","year":"2016","journal-title":"Environ. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147371","DOI":"10.1016\/j.scitotenv.2021.147371","article-title":"The effects of phthalate ester exposure on human health: A review","volume":"786","author":"Chang","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mariana, M., and Cairrao, E. (2020). Phthalates Implications in the Cardiovascular System. J. Cardiovasc. Dev. Dis., 7.","DOI":"10.3390\/jcdd7030026"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/mrd.23541","article-title":"Update about the disrupting-effects of phthalates on the human reproductive system","volume":"88","author":"Mesquita","year":"2021","journal-title":"Mol. Reprod. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s12012-017-9439-6","article-title":"Cardiovascular Response of Rat Aorta to Di-(2-ethylhexyl) Phthalate (DEHP) Exposure","volume":"18","author":"Mariana","year":"2018","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"112109","DOI":"10.1016\/j.envres.2021.112109","article-title":"Phthalate exposure and risk of diabetes mellitus: Implications from a systematic review and meta-analysis","volume":"204","author":"Zhang","year":"2022","journal-title":"Environ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9435","DOI":"10.1007\/s11356-019-04373-1","article-title":"Systematic review and meta-analysis on the association between phthalates exposure and insulin resistance","volume":"26","author":"Zarean","year":"2019","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_8","unstructured":"IDF (2021). IDF Diabetes Atlas, International Diabetes Federation. [10th ed.]. Available online: https:\/\/diabetesatlas.org\/atlas\/tenth-edition\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1289\/ehp.6202","article-title":"In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy","volume":"111","author":"Latini","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00204-005-0674-4","article-title":"Detection of phthalate metabolites in human saliva","volume":"79","author":"Silva","year":"2005","journal-title":"Arch. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1289\/ehp.8075","article-title":"Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age","volume":"114","author":"Main","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"69","DOI":"10.6065\/apem.2014.19.2.69","article-title":"Phthalate exposure and childhood obesity","volume":"19","author":"Kim","year":"2014","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148898","DOI":"10.1016\/j.scitotenv.2021.148898","article-title":"Prenatal phthalate exposure measurement: A comparison of metabolites quantified in prenatal maternal urine and newborn\u2019s meconium","volume":"796","author":"Mathew","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106987","DOI":"10.1016\/j.envint.2021.106987","article-title":"Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid","volume":"158","author":"Brauner","year":"2022","journal-title":"Environ. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.jhazmat.2017.06.036","article-title":"Phthalates impact human health: Epidemiological evidences and plausible mechanism of action","volume":"340","author":"Benjamin","year":"2017","journal-title":"J. Hazard. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S617","DOI":"10.33549\/physiolres.934794","article-title":"Steroids, steroid associated substances and gestational diabetes mellitus","volume":"70","author":"Hill","year":"2021","journal-title":"Physiol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4239\/wjd.v8.i12.489","article-title":"Gestational diabetes from A to Z","volume":"8","author":"Doupis","year":"2017","journal-title":"World J. Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Filardi, T., Panimolle, F., Lenzi, A., and Morano, S. (2020). Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications. Nutrients, 12.","DOI":"10.3390\/nu12020525"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133855","DOI":"10.1016\/j.scitotenv.2019.133855","article-title":"Association of self-reported personal care product use with blood glucose levels measured during pregnancy among women from a fertility clinic","volume":"695","author":"Bellavia","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12940-022-00858-8","article-title":"Endocrine-disrupting chemicals and the risk of gestational diabetes mellitus: A systematic review and meta-analysis","volume":"21","author":"Yan","year":"2022","journal-title":"Environ. Health"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Predieri, B., Bruzzi, P., Bigi, E., Ciancia, S., Madeo, S.F., Lucaccioni, L., and Iughetti, L. (2020). Endocrine Disrupting Chemicals and Type 1 Diabetes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082937"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1136\/jech-2018-210627","article-title":"Exposure to environmental chemicals and type 1 diabetes: An update","volume":"73","author":"Howard","year":"2019","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3389\/fendo.2018.00513","article-title":"Developmental Exposure to Endocrine Disrupting Chemicals and Type 1 Diabetes Mellitus","volume":"9","author":"Howard","year":"2018","journal-title":"Front. Endocrinol. Lausanne"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Del Chierico, F., Rapini, N., Deodati, A., Matteoli, M.C., Cianfarani, S., and Putignani, L. (2022). Pathophysiology of Type 1 Diabetes and Gut Microbiota Role. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314650"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.7150\/thno.65778","article-title":"Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications","volume":"12","author":"Liu","year":"2022","journal-title":"Theranostics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.suc.2011.08.007","article-title":"Tipping the balance: The pathophysiology of obesity and type 2 diabetes mellitus","volume":"91","author":"McKenney","year":"2011","journal-title":"Surg. Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.envint.2016.09.009","article-title":"Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors","volume":"96","author":"Meeker","year":"2016","journal-title":"Environ. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107099","DOI":"10.1016\/j.envint.2022.107099","article-title":"Urinary phthalate and DINCH metabolite concentrations and gradations of maternal glucose intolerance","volume":"161","author":"Ponzano","year":"2022","journal-title":"Environ. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ijheh.2018.12.005","article-title":"Pregnancy phthalate metabolite concentrations and infant birth weight by gradations of maternal glucose tolerance","volume":"222","author":"Noor","year":"2019","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.envint.2018.12.021","article-title":"Maternal urinary phthalate metabolites in relation to gestational diabetes and glucose intolerance during pregnancy","volume":"123","author":"Shaffer","year":"2019","journal-title":"Environ. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12940-018-0399-5","article-title":"Trimester-specific phthalate concentrations and glucose levels among women from a fertility clinic","volume":"17","author":"Chiu","year":"2018","journal-title":"Environ. Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106677","DOI":"10.1016\/j.envint.2021.106677","article-title":"Effects of single and combined gestational phthalate exposure on blood pressure, blood glucose and gestational weight gain: A longitudinal analysis","volume":"155","author":"Gao","year":"2021","journal-title":"Environ. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2147\/IJGM.S335895","article-title":"Association Between Phthalate Exposure in Pregnancy and Gestational Diabetes: A Chinese Cross-Sectional Study","volume":"15","author":"Liang","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33555","DOI":"10.1007\/s11356-022-24454-y","article-title":"Effects of exposure to phthalate during early pregnancy on gestational diabetes mellitus: A nested case-control study with propensity score matching","volume":"30","author":"Chen","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"159570","DOI":"10.1016\/j.scitotenv.2022.159570","article-title":"Serum concentrations of phthalate metabolites in pregnant women and their association with gestational diabetes mellitus and blood glucose levels","volume":"857","author":"Wang","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fendo.2018.00099","article-title":"Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors for Gestational Diabetes Mellitus","volume":"9","author":"Fisher","year":"2018","journal-title":"Front. Endocrinol. Lausanne"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Martinez-Ibarra, A., Martinez-Razo, L.D., Vazquez-Martinez, E.R., Martinez-Cruz, N., Flores-Ramirez, R., Garcia-Gomez, E., Lopez-Lopez, M., Ortega-Gonzalez, C., Camacho-Arroyo, I., and Cerbon, 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_38","doi-asserted-by":"crossref","first-page":"106612","DOI":"10.1016\/j.envint.2021.106612","article-title":"The associations of phthalate biomarkers during pregnancy with later glycemia and lipid profiles","volume":"155","author":"Wu","year":"2021","journal-title":"Environ. Int."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Guo, J., Wu, M., Gao, X., Chen, J., Li, S., Chen, B., and Dong, R. (2020). Meconium Exposure to Phthalates, Sex and Thyroid Hormones, Birth Size and Pregnancy Outcomes in 251 Mother-Infant Pairs from Shanghai. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17217711"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107078","DOI":"10.1016\/j.envint.2022.107078","article-title":"Prenatal phthalate exposure in relation to placental corticotropin releasing hormone (pCRH) in the CANDLE cohort","volume":"160","author":"Barrett","year":"2022","journal-title":"Environ. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.envint.2015.05.016","article-title":"Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study","volume":"83","author":"Shapiro","year":"2015","journal-title":"Environ. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ijheh.2015.01.005","article-title":"Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy","volume":"218","author":"Robledo","year":"2015","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110712","DOI":"10.1016\/j.envres.2021.110712","article-title":"Prenatal exposure to phthalates and maternal metabolic outcomes in a high-risk pregnant Latina population","volume":"194","author":"Zukin","year":"2021","journal-title":"Environ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111154","DOI":"10.1016\/j.ecoenv.2020.111154","article-title":"Maternal exposure to Di-n-butyl phthalate (DBP) aggravate gestational diabetes mellitus via FoxM1 suppression by pSTAT1 signalling","volume":"205","author":"Chen","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"John, C.M., Mohamed Yusof, N.I.S., Abdul Aziz, S.H., and Mohd Fauzi, F. (2018). Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus-A Review of Potential Contributing Mechanisms. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123894"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"606","DOI":"10.2337\/db07-1356","article-title":"Increased skeletal muscle tumor necrosis factor-alpha and impaired insulin signaling persist in obese women with gestational diabetes mellitus 1 year postpartum","volume":"57","author":"Friedman","year":"2008","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"153932","DOI":"10.1016\/j.scitotenv.2022.153932","article-title":"Associating diethylhexyl phthalate to gestational diabetes mellitus via adverse outcome pathways using a network-based approach","volume":"824","author":"Zhang","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1002\/jat.2902","article-title":"Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: An in silico approach","volume":"34","author":"Pradeep","year":"2014","journal-title":"J. Appl. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mce.2009.02.017","article-title":"PPAR-mediated activity of phthalates: A link to the obesity epidemic?","volume":"304","author":"Desvergne","year":"2009","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Park, H.Y., Bae, S., Lim, Y.H., and Hong, Y.C. (2013). Diethylhexyl phthalates is associated with insulin resistance via oxidative stress in the elderly: A panel study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071392"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.mce.2015.03.003","article-title":"Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro","volume":"407","author":"Cho","year":"2015","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev-physiol-012110-142200","article-title":"Endocrine disruptors: From endocrine to metabolic disruption","volume":"73","author":"Desvergne","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"208947","DOI":"10.1155\/2015\/208947","article-title":"Can exposure to environmental chemicals increase the risk of diabetes type 1 development?","volume":"2015","author":"Bodin","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17915","DOI":"10.1007\/s11356-018-1997-z","article-title":"Phthalates and type 1 diabetes: Is there any link?","volume":"25","author":"Norberto","year":"2018","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.toxrep.2015.02.010","article-title":"Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice","volume":"2","author":"Bodin","year":"2015","journal-title":"Toxicol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4614379","DOI":"10.1155\/2017\/4614379","article-title":"Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic beta-Cell Function","volume":"2017","author":"Weldingh","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4161\/isl.19747","article-title":"Selective estrogen receptor modulation in pancreatic beta-cells and the prevention of type 2 diabetes","volume":"4","author":"Tiano","year":"2012","journal-title":"Islets"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.toxlet.2017.05.028","article-title":"Agonistic and antagonistic effects of phthalates and their urinary metabolites on the steroid hormone receptors ERalpha, ERbeta, and AR","volume":"277","author":"Engel","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1210\/en.2014-1436","article-title":"Identification of hot spots of DNA methylation in the adult male adrenal in response to in utero exposure to the ubiquitous endocrine disruptor plasticizer di-(2-ethylhexyl) phthalate","volume":"156","author":"Papadopoulos","year":"2015","journal-title":"Endocrinology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3389\/fendo.2020.00125","article-title":"Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms","volume":"11","author":"Zhou","year":"2020","journal-title":"Front. Endocrinol. Lausanne"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40168-016-0173-2","article-title":"Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model","volume":"4","author":"Hu","year":"2016","journal-title":"Microbiome"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"261","DOI":"10.4142\/jvs.2017.18.3.261","article-title":"Calcium homeostasis in diabetes mellitus","volume":"18","author":"Ahn","year":"2017","journal-title":"J. Vet. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4062","DOI":"10.1210\/jc.2016-2134","article-title":"Relationships Between Urinary Phthalate Metabolite and Bisphenol A Concentrations and Vitamin D Levels in U.S. Adults: National Health and Nutrition Examination Survey (NHANES), 2005\u20132010","volume":"101","author":"Johns","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"087026","DOI":"10.1289\/EHP1178","article-title":"Urinary BPA and Phthalate Metabolite Concentrations and Plasma Vitamin D Levels in Pregnant Women: A Repeated Measures Analysis","volume":"125","author":"Johns","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.biochi.2020.05.002","article-title":"Acute exposure to bis(2-ethylhexyl)phthalate disrupts calcium homeostasis, energy metabolism and induces oxidative stress in the testis of Danio rerio","volume":"175","author":"Dambros","year":"2020","journal-title":"Biochimie"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.taap.2005.09.012","article-title":"Butyl benzyl phthalate blocks Ca2+ signaling coupled with purinoceptor in rat PC12 cells","volume":"210","author":"Liu","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0165-2478(01)00318-2","article-title":"Effect of dialkyl phthalates on the degranulation and Ca2+ response of RBL-2H3 mast cells","volume":"80","author":"Nakamura","year":"2002","journal-title":"Immunol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Posnack, N.G., Idrees, R., Ding, H., Jaimes, R., Stybayeva, G., Karabekian, Z., Laflamme, M.A., and Sarvazyan, N. (2015). Exposure to phthalates affects calcium handling and intercellular connectivity of human stem cell-derived cardiomyocytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121927"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"106063","DOI":"10.1016\/j.envint.2020.106063","article-title":"Fetal phthalates and bisphenols and childhood lipid and glucose metabolism. A population-based prospective cohort study","volume":"144","author":"Sol","year":"2020","journal-title":"Environ. Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1210\/jc.2015-1686","article-title":"Association of Exposure to Di-2-Ethylhexylphthalate Replacements With Increased Insulin Resistance in Adolescents From NHANES 2009\u20132012","volume":"100","author":"Attina","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1530\/EC-17-0344","article-title":"Bisphenol A, phthalate metabolites and glucose homeostasis in healthy normal-weight children","volume":"7","author":"Carlsson","year":"2018","journal-title":"Endocr. Connect."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.envpol.2017.03.037","article-title":"Mono-2-ethylhexyl phthalate associated with insulin resistance and lower testosterone levels in a young population","volume":"225","author":"Chen","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.scitotenv.2017.09.009","article-title":"The associations between phthalate exposure and insulin resistance, beta-cell function and blood glucose control in a population-based sample","volume":"612","author":"Dales","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.envres.2015.01.010","article-title":"Urinary phthalate metabolites are associated with insulin resistance in obese subjects","volume":"137","author":"Dirinck","year":"2015","journal-title":"Environ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.35371\/aoem.2020.32.e34","article-title":"Relationship between urinary phthalate metabolites and diabetes: Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015\u20132017)","volume":"32","author":"Nam","year":"2020","journal-title":"Ann. Occup. Environ. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.scitotenv.2019.03.192","article-title":"Association between phthalate exposure and glycosylated hemoglobin, fasting glucose, and type 2 diabetes mellitus: A case-control study in China","volume":"670","author":"Duan","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Dong, R., Zhao, S., Zhang, H., Chen, J., Zhang, M., Wang, M., Wu, M., Li, S., and Chen, B. (2017). Sex Differences in the Association of Urinary Concentrations of Phthalates Metabolites with Self-Reported Diabetes and Cardiovascular Diseases in Shanghai Adults. Int. J. Environ. Res. Public Health, 14.","DOI":"10.3390\/ijerph14060598"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"28743","DOI":"10.1007\/s11356-021-18361-x","article-title":"Screening the incidence of diabetogensis with urinary phthalate in Saudi subjects","volume":"29","author":"Kumosani","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.envres.2017.06.021","article-title":"The association between total phthalate concentration and non-communicable diseases and chronic inflammation in South Australian urban dwelling men","volume":"158","author":"Bai","year":"2017","journal-title":"Environ. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.envres.2011.05.015","article-title":"Phthalate exposure associated with self-reported diabetes among Mexican women","volume":"111","author":"Svensson","year":"2011","journal-title":"Environ. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1289\/ehp.1104717","article-title":"Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001\u20132008","volume":"120","author":"Stahlhut","year":"2012","journal-title":"Environ. Health Perspect."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1289\/ehp.1307201","article-title":"Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: A prospective investigation in the Nurses\u2032 Health Study (NHS) and NHSII cohorts","volume":"122","author":"Sun","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"106609","DOI":"10.1016\/j.envint.2021.106609","article-title":"Perturbation of serum metabolome in relation to type 2 diabetes mellitus and urinary levels of phthalate metabolites and bisphenols","volume":"155","author":"Duan","year":"2021","journal-title":"Environ. Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"110316","DOI":"10.1016\/j.envres.2020.110316","article-title":"SGLT2 inhibitors and thiazide enhance excretion of DEHP toxic metabolites in subjects with type 2 diabetes: A randomized clinical trial","volume":"192","author":"Mengozzi","year":"2021","journal-title":"Environ. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.toxlet.2014.09.025","article-title":"Gestational exposure to di(2-ethylhexyl) phthalate (DEHP) impairs pancreatic beta-cell function in F1 rat offspring","volume":"232","author":"Rajesh","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/jat.3764","article-title":"Maternal di-(2-ethylhexyl) phthalate exposure alters hepatic insulin signal transduction and glucoregulatory events in rat F(1) male offspring","volume":"39","author":"Rajagopal","year":"2019","journal-title":"J. Appl. Toxicol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.tox.2018.12.004","article-title":"Developmental exposure to DEHP alters hepatic glucose uptake and transcriptional regulation of GLUT2 in rat male offspring","volume":"413","author":"Rajagopal","year":"2019","journal-title":"Toxicology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2018.03.004","article-title":"Dibutyl phthalate exposure aggravates type 2 diabetes by disrupting the insulin-mediated PI3K\/AKT signaling pathway","volume":"290","author":"Deng","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"112003","DOI":"10.1016\/j.fct.2021.112003","article-title":"Di-(2-ethylhexyl) phthalate-induced hepatotoxicity exacerbated type 2 diabetes mellitus (T2DM) in female pubertal T2DM mice","volume":"149","author":"Ding","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1007\/s00204-019-02590-8","article-title":"Transcriptome analysis revealed the mechanism of the metabolic toxicity and susceptibility of di-(2-ethylhexyl)phthalate on adolescent male ICR mice with type 2 diabetes mellitus","volume":"93","author":"Ding","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/toxres\/tfab045","article-title":"The possible effects of mono butyl phthalate (MBP) and mono (2-ethylhexyl) phthalate (MEHP) on INS-1 pancreatic beta cells","volume":"10","author":"Karabulut","year":"2021","journal-title":"Toxicol. Res. Camb"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.fct.2016.04.023","article-title":"Low dose monoethyl phthalate (MEP) exposure triggers proliferation by activating PDX-1 at 1.1B4 human pancreatic beta cells","volume":"93","author":"Guven","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Al-Abdulla, R., Ferrero, H., Soriano, S., Boronat-Belda, T., and Alonso-Magdalena, P. (2022). Screening of Relevant Metabolism-Disrupting Chemicals on Pancreatic beta-Cells: Evaluation of Murine and Human In Vitro Models. Int. J. Mol. Sci., 23.","DOI":"10.1101\/2022.03.22.485270"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1177\/0960327120909526","article-title":"Long-term dietary administration of diethyl phthalate triggers loss of insulin sensitivity in two key insulin target tissues of mice","volume":"39","author":"Mondal","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"107279","DOI":"10.1016\/j.envint.2022.107279","article-title":"Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARgamma activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes","volume":"164","author":"Schaffert","year":"2022","journal-title":"Environ. Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cbi.2017.01.015","article-title":"The role of oxidative stress in DNA damage in pancreatic beta cells induced by di-(2-ethylhexyl) phthalate","volume":"265","author":"She","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"114396","DOI":"10.1016\/j.ecoenv.2022.114396","article-title":"Dibutyl phthalate affects insulin synthesis and secretion by regulating the mitochondrial apoptotic pathway and oxidative stress in rat insulinoma cells","volume":"249","author":"Yang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tox.2017.05.005","article-title":"Effects of DEHP and its metabolite MEHP on insulin signalling and proteins involved in GLUT4 translocation in cultured L6 myotubes","volume":"386","author":"Viswanathan","year":"2017","journal-title":"Toxicology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.taap.2016.12.010","article-title":"Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARgamma","volume":"316","author":"Zhang","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"112325","DOI":"10.1016\/j.fct.2021.112325","article-title":"Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: Merging bioinformatics with in vivo analysis","volume":"154","author":"Baralic","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12199-019-0802-z","article-title":"Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: A review","volume":"24","author":"Ito","year":"2019","journal-title":"Environ. Health Prev. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.envint.2017.09.002","article-title":"Exposure to phthalates in patients with diabetes and its association with oxidative stress, adiponectin, and inflammatory cytokines","volume":"109","author":"Duan","year":"2017","journal-title":"Environ. Int."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.envint.2019.01.082","article-title":"Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia","volume":"126","author":"Li","year":"2019","journal-title":"Environ. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.envint.2018.09.028","article-title":"The role of oxidative stress in cardiometabolic risk related to phthalate exposure in elderly diabetic patients from Shanghai","volume":"121","author":"Dong","year":"2018","journal-title":"Environ. Int."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s12020-016-1158-4","article-title":"The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders","volume":"55","author":"Stojanoska","year":"2017","journal-title":"Endocrine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1097\/PRS.0b013e3181f44abc","article-title":"Observational studies: Cohort and case-control studies","volume":"126","author":"Song","year":"2010","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.envres.2014.06.009","article-title":"Serum levels of monobenzylphthalate (MBzP) is related to carotid atherosclerosis in the elderly","volume":"133","author":"Wiberg","year":"2014","journal-title":"Environ. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1136\/jech-2016-208006","article-title":"Population attributable risks and costs of diabetogenic chemical exposures in the elderly","volume":"71","author":"Trasande","year":"2017","journal-title":"J. Epidemiol. Community Health"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/6\/746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:52:39Z","timestamp":1760125959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/6\/746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,11]]},"references-count":108,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["metabo13060746"],"URL":"https:\/\/doi.org\/10.3390\/metabo13060746","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,11]]}}}