Insulin Resistance in Children and the role of Endocrine-Disrupting Chemicals: Taking Stock of the Situation

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Francesca Forcucci Francesco Chiarelli

Abstract

The prevalence of non-communicable diseases, of which insulin resistance is a major constituent, among the pediatric population is exponentially increasing worldwide; this is causing a significant health burden, making understanding the basis of this phenomenon an issue of primary importance. During the last decades, we also observed that exposure to endocrine-disrupting chemicals is becoming more and more common; this has led researchers to investigate the mechanism of action and define the role of those substances in interfering with human metabolism and hormonal balance, especially at a young age. We reviewed the literature on prospective, epidemiological, and cross-sectional studies that have shown a link between exposure to pesticides, polychlorinated biphenyls, bisphenol A, phthalates, aromatic polycyclic hydrocarbons, or dioxins and insulin resistance; the strength of the associations varies between the substances and human biomonitoring studies have helped in defining the role of these chemicals. The number of prospective studies in children and even in adults is still low and heterogenous, still, evidence that Endocrine disruptors might be involved in the development of insulin resistance and related diseases is accumulating. This review aims to analyze the latest findings linking exposure to endocrine-disrupting chemicals with insulin resistance in children with the perspective of taking a cue for conducting new studies and identifying the most concerning Endocrine disruptors exposures, in order to guide future risk assessment and policy action aimed to limit the negative consequences of endocrine disrupting chemical exposure.

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How to Cite
FORCUCCI, Francesca; CHIARELLI, Francesco. Insulin Resistance in Children and the role of Endocrine-Disrupting Chemicals: Taking Stock of the Situation. Medical Research Archives, [S.l.], v. 11, n. 5, may 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3728>. Date accessed: 25 apr. 2024. doi: https://doi.org/10.18103/mra.v11i5.3728.
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Research Articles

References

[1] Groh KJ, Geueke B, Martin O, Maffini M, Muncke J. Overview of intentionally used food contact chemicals and their hazards. Environ Int. 2021;150:106225. doi:10.1016/j.envint.2020.106225
[2] Reaven GM. Pathophysiology of insulin resistance in human disease. Physiol Rev. 1995;75(3):473-486. doi:10.1152/physrev.1995.75.3.473
[3] Woodruff TJ, Zota AR, Schwartz JM. Environmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004. Environ Health Perspect. 2011;119(6):878-885. doi:10.1289/ehp.1002727
[4] Braun JM, Kalkbrenner AE, Just AC, Yolton K, Calafat AM, Sjödin A, et al. Gestational Exposure to Endocrine-Disrupting Chemicals and Reciprocal Social, Repetitive, and Stereotypic Behaviors in 4- and 5-Year-Old Children: The HOME Study. Environ Health Perspect. 2014;122(5):513-520. doi:10.1289/ehp.1307261
[5] Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, et al. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth. Environ Health Perspect. 2014;122(10):1040-1051. doi:10.1289/ehp.1307923
[6] Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA, et al. Metabolism disrupting chemicals and metabolic disorders. Reproductive Toxicology. 2017;68:3-33. doi:10.1016/j.reprotox.2016.10.001
[7] la Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, et al. Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol. 2020;16(1):45-57. doi:10.1038/s41574-019-0273-8
[8] Cresteil T. Onset of xenobiotic metabolism in children: Toxicological implications. Food Addit Contam. 1998;15(sup001):45-51. doi:10.1080/02652039809374614
[9] Hakkola J, Tanaka E, Pelkonen O. Developmental Expression of Cytochrome P450 Enzymes in Human Liver. Pharmacol Toxicol. 1998;82(5):209-217. doi:10.1111/j.1600-0773.1998.tb01427.x
[10] Lamb JC, Boffetta P, Foster WG, Goodman JE, Hentz KL, Rhomberg LR, et al. Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals – 2012. Regulatory Toxicology and Pharmacology. 2014;69(1):22-40. doi:10.1016/j.yrtph.2014.02.002
[11] Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, et al. Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society. Endocrinology. 2012;153(9):4097-4110. doi:10.1210/en.2012-1422
[12] Woodruff TJ, Zeise L, Axelrad DA, Guyton KZ, Janssen S, Miller M, et al. Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making. Environ Health Perspect. 2008;116(11):1568-1575. doi:10.1289/ehp.11516
[13] Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, et al. Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology. Reproductive Toxicology. 2013;38:1-15. doi:10.1016/j.reprotox.2013.02.002
[14] Günther K, Räcker T, Böhme R. An Isomer-Specific Approach to Endocrine-Disrupting Nonylphenol in Infant Food. J Agric Food Chem. 2017;65(6):1247-1254. doi:10.1021/acs.jafc.6b04916
[15] Vandenberg LN, Ågerstrand M, Beronius A, Beausoleil C, Bergman Å, Bero LA, et al. A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals. Environmental Health. 2016;15(1):74. doi:10.1186/s12940-016-0156-6
[16] Barton-Maclaren TS, Wade M, Basu N, Bayen S, Grundy J, Marlatt V, et al. Innovation in regulatory approaches for endocrine disrupting chemicals: The journey to risk assessment modernization in Canada. Environ Res. 2022;204:112225. doi:10.1016/j.envres.2021.112225
[17] European Cluster to Improve Identification of Endocrine Disruptors (EURION). New Testing and Screening Methods to Identify Endocrine Disrupting Chemicals (EDCs). https://eurion-cluster.eu/.
[18] Gomes JM, Almeida TFA, da Silva TA, de Lourdes Cardeal Z, Menezes HC. Saliva biomonitoring using LPME-GC/MS method to assess dentistry exposure to plasticizers. Anal Bioanal Chem. 2020;412(28):7799-7810. doi:10.1007/s00216-020-02908-x
[19] Abafe OA, Macheka LR, Olowoyo JO. Confirmatory Analysis of Per and Polyfluoroalkyl Substances in Milk and Infant Formula Using UHPLC–MS/MS. Molecules. 2021;26(12):3664. doi:10.3390/molecules26123664
[20] Riboni N, Fornari F, Bianchi F, Careri M. A simple and efficient Solid-Phase Microextraction – Gas Chromatography – Mass Spectrometry method for the determination of fragrance materials at ultra-trace levels in water samples using multi-walled carbon nanotubes as innovative coating. Talanta. 2021;224:121891. doi:10.1016/j.talanta.2020.121891
[21] Singh S, Li SSL. Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates. Int J Mol Sci. 2012;13(8):10143-10153. doi:10.3390/ijms130810143
[22] Commission Regulation (EU) No 10/2011. Plastic Materials and Articles Intended to Come into Contact with Food. : https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=celex%3A32011R0010.
[23] Murata M, Kang JH. Bisphenol A (BPA) and cell signaling pathways. Biotechnol Adv. 2018;36(1):311-327. doi:10.1016/j.biotechadv.2017.12.002
[24] Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, et al. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses. Endocr Rev. 2012;33(3):378-455. doi:10.1210/er.2011-1050
[25] Zhou Q, Miao M, Ran M, Ding L, Bai L, Wu T, et al. Serum bisphenol-A concentration and sex hormone levels in men. Fertil Steril. 2013;100(2):478-482. doi:10.1016/j.fertnstert.2013.04.017
[26] Mendiola J, Jørgensen N, Andersson AM, Calafat AM, Ye X, Redmon JB, et al. Are Environmental Levels of Bisphenol A Associated with Reproductive Function in Fertile Men? Environ Health Perspect. 2010;118(9):1286-1291. doi:10.1289/ehp.1002037
[27] Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev. 2015;36(6):E1-E150. doi:10.1210/er.2015-1010
[28] Masuyama H, Hiramatsu Y. Involvement of Suppressor for Gal 1 in the Ubiquitin/Proteasome-mediated Degradation of Estrogen Receptors. Journal of Biological Chemistry. 2004;279(13):12020-12026. doi:10.1074/jbc.M312762200
[29] Soriano S, Alonso-Magdalena P, García-Arévalo M, Novials A, Muhammed SJ, Salehi A, et al. Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor β. PLoS One. 2012;7(2):e31109. doi:10.1371/journal.pone.0031109
[30] Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquié M, Gauthier BR, et al. Pancreatic Insulin Content Regulation by the Estrogen Receptor ERα. PLoS One. 2008;3(4):e2069. doi:10.1371/journal.pone.0002069
[31] Chen D, Kannan K, Tan H, Zheng Z, Feng YL, Wu Y, et al. Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity—A Review. Environ Sci Technol. 2016;50(11):5438-5453. doi:10.1021/acs.est.5b05387
[32] Silano V, Barat Baviera JM, Bolognesi C, Chesson A, Cocconcelli PS, Crebelli R, et al. Update of the risk assessment of di‐butylphthalate (DBP), butyl‐benzyl‐phthalate (BBP), bis(2‐ethylhexyl)phthalate (DEHP), di‐isononylphthalate (DINP) and di‐isodecylphthalate (DIDP) for use in food contact materials. EFSA Journal. 2019;17(12). doi:10.2903/j.efsa.2019.5838
[33] Rudel RA, Gray JM, Engel CL, Rawsthorne TW, Dodson RE, Ackerman JM, et al. Food Packaging and Bisphenol A and Bis(2-Ethyhexyl) Phthalate Exposure: Findings from a Dietary Intervention. Environ Health Perspect. 2011;119(7):914-920. doi:10.1289/ehp.1003170
[34] Langer S, Bekö G, Weschler CJ, Brive LM, Toftum J, Callesen M, et al. Phthalate metabolites in urine samples from Danish children and correlations with phthalates in dust samples from their homes and daycare centers. Int J Hyg Environ Health. 2014;217(1):78-87. doi:10.1016/j.ijheh.2013.03.014
[35] Bornehag CG, Lundgren B, Weschler CJ, Sigsgaard T, Hagerhed-Engman L, Sundell J. Phthalates in Indoor Dust and Their Association with Building Characteristics. Environ Health Perspect. 2005;113(10):1399-1404. doi:10.1289/ehp.7809
[36] Braun JM, Just AC, Williams PL, Smith KW, Calafat AM, Hauser R. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic. J Expo Sci Environ Epidemiol. 2014;24(5):459-466. doi:10.1038/jes.2013.69
[37] Singh AR, Lawrence WH, Autianx J. Maternal-Fetal Transfer of 14C-Di-2-ethylhexyl Phthalate and 14C-Diethyl Phthalate in Rats. J Pharm Sci. 1975;64(8):1347-1350. doi:10.1002/jps.2600640819
[38] Gray TJB, Beamand JA. Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Food and Chemical Toxicology. 1984;22(2):123-131. doi:10.1016/0278-6915(84)90092-9
[39] Calafat AM. Contemporary Issues in Exposure Assessment Using Biomonitoring. Curr Epidemiol Rep. 2016;3(2):145-153. doi:10.1007/s40471-016-0075-7
[40] Perrier F, Giorgis-Allemand L, Slama R, Philippat C. Within-subject Pooling of Biological Samples to Reduce Exposure Misclassification in Biomarker-based Studies. Epidemiology. 2016;27(3):378-388. doi:10.1097/EDE.0000000000000460
[41] Martinez-Arguelles DB, Culty M, Zirkin BR, Papadopoulos V. In Utero Exposure to Di-(2-Ethylhexyl) Phthalate Decreases Mineralocorticoid Receptor Expression in the Adult Testis. Endocrinology. 2009;150(12):5575-5585. doi:10.1210/en.2009-0847
[42] Wójtowicz AK, Sitarz-Głownia AM, Szczęsna M, Szychowski KA. The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling. Neurotox Res. 2019;35(1):183-195. doi:10.1007/s12640-018-9946-7
[43] Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and their salts Scientific Opinion of the Panel on Contaminants in the Food chain. EFSA Journal. 2008;6(7). doi:10.2903/j.efsa.2008.653
[44] Buck RC, Franklin J, Berger U, Conder JM, Cousins IT, de Voogt P, et al. Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins. Integr Environ Assess Manag. 2011;7(4):513-541. doi:10.1002/ieam.258
[45] Braun JM. Early-life exposure to EDCs: role in childhood obesity and neurodevelopment. Nat Rev Endocrinol. 2017;13(3):161-173. doi:10.1038/nrendo.2016.186
[46] Rodricks J v., Swenberg JA, Borzelleca JF, Maronpot RR, Shipp AM. Triclosan: A critical review of the experimental data and development of margins of safety for consumer products. Crit Rev Toxicol. 2010;40(5):422-484. doi:10.3109/10408441003667514
[47] Sandborgh-Englund G, Adolfsson-Erici M, Odham G, Ekstrand J. Pharmacokinetics of Triclosan Following Oral Ingestion in Humans. J Toxicol Environ Health A. 2006;69(20):1861-1873. doi:10.1080/15287390600631706
[48] Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Urinary Concentrations of Triclosan in the U.S. Population: 2003–2004. Environ Health Perspect. 2008;116(3):303-307. doi:10.1289/ehp.10768
[49] Casas L, Fernández MF, Llop S, Guxens M, Ballester F, Olea N, et al. Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children. Environ Int. 2011;37(5):858-866. doi:10.1016/j.envint.2011.02.012
[50] Miller MD, Marty MA, Arcus A, Brown J, Morry D, Sandy M. Differences Between Children and Adults: Implications for Risk Assessment at California EPA. Int J Toxicol. 2002;21(5):403-418. doi:10.1080/10915810290096630
[51] Botton J, Kadawathagedara M, de Lauzon-Guillain B. Endocrine disrupting chemicals and growth of children. Ann Endocrinol (Paris). 2017;78(2):108-111. doi:10.1016/j.ando.2017.04.009
[52] DeFronzo RA. Pathogenesis of Type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia. 1992;35(4):389-397. doi:10.1007/BF00401208
[53] Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, Marcovecchio ML, et al. Insulin Resistance in Children: Consensus, Perspective, and Future Directions. J Clin Endocrinol Metab. 2010;95(12):5189-5198. doi:10.1210/jc.2010-1047
[54] Bacha F, Saad R, Gungor N, Arslanian SA. Are Obesity-Related Metabolic Risk Factors Modulated by the Degree of Insulin Resistance in Adolescents? Diabetes Care. 2006;29(7):1599-1604. doi:10.2337/dc06-0581
[55] Arslanian S, Suprasongsin C. Insulin sensitivity, lipids, and body composition in childhood: is “syndrome X” present? J Clin Endocrinol Metab. 1996;81(3):1058-1062. doi:10.1210/jcem.81.3.8772576
[56] Bacha F, Saad R, Gungor N, Janosky J, Arslanian SA. Obesity, Regional Fat Distribution, and Syndrome X in Obese Black Versus White Adolescents: Race Differential in Diabetogenic and Atherogenic Risk Factors. J Clin Endocrinol Metab. 2003;88(6):2534-2540. doi:10.1210/jc.2002-021267
[57] Weiss R, Dufour S, Taksali SE, Tamborlane W v, Petersen KF, Bonadonna RC, et al. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. The Lancet. 2003;362(9388):951-957. doi:10.1016/S0140-6736(03)14364-4
[58] Deivanayagam S, Mohammed BS, Vitola BE, Naguib GH, Keshen TH, Kirk EP, et al. Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents. Am J Clin Nutr. 2008;88(2):257-262. doi:10.1093/ajcn/88.2.257
[59] Perseghin G, Bonfanti R, Magni S, Lattuada G, de Cobelli F, Canu T, et al. Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease. American Journal of Physiology-Endocrinology and Metabolism. 2006;291(4):E697-E703. doi:10.1152/ajpendo.00017.2006
[60] Weigensberg MJ, Ball GDC, Shaibi GQ, Cruz ML, Gower BA, Goran MI. Dietary Fat Intake and Insulin Resistance in Black and White Children. Obes Res. 2005;13(9):1630-1637. doi:10.1038/oby.2005.200
[61] Fu L, Xie N, Qu F, Zhou J, Wang F. The Association Between Polycystic Ovary Syndrome and Metabolic Syndrome in Adolescents: a Systematic Review and Meta-analysis. Reproductive Sciences. 2023;30(1):28-40. doi:10.1007/s43032-022-00864-8
[62] Silfen ME, Denburg MR, Manibo AM, Lobo RA, Jaffe R, Ferin M, et al. Early Endocrine, Metabolic, and Sonographic Characteristics of Polycystic Ovary Syndrome (PCOS): Comparison between Nonobese and Obese Adolescents. J Clin Endocrinol Metab. 2003;88(10):4682-4688. doi:10.1210/jc.2003-030617
[63] Poulsen P, Levin K, Petersen I, Christensen K, Beck-Nielsen H, Vaag A. Heritability of Insulin Secretion, Peripheral and Hepatic Insulin Action, and Intracellular Glucose Partitioning in Young and Old Danish Twins. Diabetes. 2005;54(1):275-283. doi:10.2337/diabetes.54.1.275
[64] Souren NY, Paulussen ADC, Loos RJF, Gielen M, Beunen G, Fagard R, et al. Anthropometry, carbohydrate and lipid metabolism in the East Flanders Prospective Twin Survey: heritabilities. Diabetologia. 2007;50(10):2107-2116. doi:10.1007/s00125-007-0784-z
[65] Chiarelli F, Marcovecchio ML. Insulin resistance and obesity in childhood. Eur J Endocrinol. 2008;159(suppl_1):S67-S74. doi:10.1530/EJE-08-0245
[66] Heindel JJ, vom Saal FS, Blumberg B, Bovolin P, Calamandrei G, Ceresini G, et al. Parma consensus statement on metabolic disruptors. Environ Health. 2015;14:54. doi:10.1186/s12940-015-0042-7
[67] Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA, et al. Metabolism disrupting chemicals and metabolic disorders. Reproductive Toxicology. 2017;68:3-33. doi:10.1016/j.reprotox.2016.10.001
[68] Darbre PD. Endocrine Disruptors and Obesity. Curr Obes Rep. 2017;6(1):18-27. doi:10.1007/s13679-017-0240-4
[69] Grün F, Blumberg B. Endocrine disrupters as obesogens. Mol Cell Endocrinol. 2009;304(1-2):19-29. doi:10.1016/j.mce.2009.02.018
[70] Papalou O, Kandaraki EA, Papadakis G, Diamanti-Kandarakis E. Endocrine Disrupting Chemicals: An Occult Mediator of Metabolic Disease. Front Endocrinol (Lausanne). 2019;10. doi:10.3389/fendo.2019.00112
[71] Tontonoz P, Spiegelman BM. Fat and Beyond: The Diverse Biology of PPARγ. Annu Rev Biochem. 2008;77(1):289-312. doi:10.1146/annurev.biochem.77.061307.091829
[72] Street M, Angelini S, Bernasconi S, Burgio E, Cassio A, Catellani C, et al. Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting. Int J Mol Sci. 2018;19(6):1647. doi:10.3390/ijms19061647
[73] Iughetti L, Lucaccioni L, Predieri B. Childhood obesity and environmental pollutants: a dual relationship. Acta Biomed. 2015;86(1):5-16.
[74] Heindel JJ, Howard S, Agay-Shay K, Arrebola JP, Audouze K, Babin PJ, et al. Obesity II: Establishing causal links between chemical exposures and obesity. Biochem Pharmacol. 2022;199:115015. doi:10.1016/j.bcp.2022.115015
[75] Janesick AS, Blumberg B. Obesogens: an emerging threat to public health. Am J Obstet Gynecol. 2016;214(5):559-565. doi:10.1016/j.ajog.2016.01.182
[76] Alonso-Magdalena P, Quesada I, Nadal A. Endocrine disruptors in the etiology of type 2 diabetes mellitus. Nat Rev Endocrinol. 2011;7(6):346-353. doi:10.1038/nrendo.2011.56
[77] Predieri B, Bruzzi P, Bigi E, Ciancia S, Madeo SF, Lucaccioni L, et al. Endocrine Disrupting Chemicals and Type 1 Diabetes. Int J Mol Sci. 2020;21(8):2937. doi:10.3390/ijms21082937
[78] Ohlstein JF, Strong AL, McLachlan JA, Gimble JM, Burow ME, Bunnell BA. Bisphenol A enhances adipogenic differentiation of human adipose stromal/stem cells. J Mol Endocrinol. 2014;53(3):345-353. doi:10.1530/JME-14-0052
[79] Braun JM, Li N, Arbuckle TE, Dodds L, Massarelli I, Fraser WD, et al. Association between gestational urinary bisphenol a concentrations and adiposity in young children: The MIREC study. Environ Res. 2019;172:454-461. doi:10.1016/j.envres.2019.02.038
[80] Mustieles V, Casas M, Ferrando-Marco P, Ocón-Hernández O, Reina-Pérez I, Rodríguez-Carrillo A, et al. Bisphenol A and adiposity measures in peripubertal boys from the INMA-Granada cohort. Environ Res. 2019;173:443-451. doi:10.1016/j.envres.2019.03.045
[81] Robles-Aguilera V, Gálvez-Ontiveros Y, Rodrigo L, Salcedo-Bellido I, Aguilera M, Zafra-Gómez A, et al. Factors Associated with Exposure to Dietary Bisphenols in Adolescents. Nutrients. 2021;13(5):1553. doi:10.3390/nu13051553
[82] Menale C, Grandone A, Nicolucci C, Cirillo G, Crispi S, di Sessa A, et al. Bisphenol A is associated with insulin resistance and modulates adiponectin and resistin gene expression in obese children. Pediatr Obes. 2017;12(5):380-387. doi:10.1111/ijpo.12154
[83] Soriano S, Alonso-Magdalena P, García-Arévalo M, Novials A, Muhammed SJ, Salehi A, et al. Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor β. PLoS One. 2012;7(2):e31109. doi:10.1371/journal.pone.0031109
[84] Ouyang F, Zhang GH, Du K, Shen L, Ma R, Wang X, et al. Maternal prenatal urinary bisphenol A level and child cardio-metabolic risk factors: A prospective cohort study. Environmental Pollution. 2020;265:115008. doi:10.1016/j.envpol.2020.115008
[85] Akgül S, Sur Ü, Düzçeker Y, Balcı A, Kızılkan MP, Kanbur N, et al. Bisphenol A and phthalate levels in adolescents with polycystic ovary syndrome. Gynecological Endocrinology. 2019;35(12):1084-1087. doi:10.1080/09513590.2019.1630608
[86] Berger K, Hyland C, Ames JL, Mora AM, Huen K, Eskenazi B, et al. Prenatal Exposure to Mixtures of Phthalates, Parabens, and Other Phenols and Obesity in Five-Year-Olds in the CHAMACOS Cohort. Int J Environ Res Public Health. 2021;18(4):1796. doi:10.3390/ijerph18041796
[87] Golestanzadeh M, Riahi R, Kelishadi R. Association of exposure to phthalates with cardiometabolic risk factors in children and adolescents: a systematic review and meta-analysis. Environmental Science and Pollution Research. 2019;26(35):35670-35686. doi:10.1007/s11356-019-06589-7
[88] Abdullah Soheimi SS, Abdul Rahman A, Abd Latip N, Ibrahim E, Sheikh Abdul Kadir SH. Understanding the Impact of Perfluorinated Compounds on Cardiovascular Diseases and Their Risk Factors: A Meta-Analysis Study. Int J Environ Res Public Health. 2021;18(16):8345. doi:10.3390/ijerph18168345
[89] Lauritzen HB, Larose TL, Øien T, Sandanger TM, Odland JØ, van de Bor M, et al. Prenatal exposure to persistent organic pollutants and child overweight/obesity at 5-year follow-up: a prospective cohort study. Environmental Health. 2018;17(1):9. doi:10.1186/s12940-017-0338-x
[90] McGlinchey A, Sinioja T, Lamichhane S, Sen P, Bodin J, Siljander H, et al. Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes. Environ Int. 2020;143:105935. doi:10.1016/j.envint.2020.105935
[91] Küblbeck J, Vuorio T, Niskanen J, Fortino V, Braeuning A, Abass K, et al. The EDCMET Project: Metabolic Effects of Endocrine Disruptors. Int J Mol Sci. 2020;21(8):3021. doi:10.3390/ijms21083021
[92] Legler J, Zalko D, Jourdan F, Jacobs M, Fromenty B, Balaguer P, et al. The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds. Int J Mol Sci. 2020;21(10):3480. doi:10.3390/ijms21103480
[93] Audouze K, Sarigiannis D, Alonso-Magdalena P, Brochot C, Casas M, Vrijheid M, et al. Integrative Strategy of Testing Systems for Identification of Endocrine Disruptors Inducing Metabolic Disorders—An Introduction to the OBERON Project. Int J Mol Sci. 2020;21(8):2988. doi:10.3390/ijms21082988
[94] Grün F, Blumberg B. Environmental Obesogens: Organotins and Endocrine Disruption via Nuclear Receptor Signaling. Endocrinology. 2006;147(6):s50-s55. doi:10.1210/en.2005-1129
[95] Egusquiza RJ, Blumberg B. Environmental Obesogens and Their Impact on Susceptibility to Obesity: New Mechanisms and Chemicals. Endocrinology. 2020;161(3). doi:10.1210/endocr/bqaa024
[96] Botton J, Kadawathagedara M, de Lauzon-Guillain B. Endocrine disrupting chemicals and growth of children. Ann Endocrinol (Paris). 2017;78(2):108-111. doi:10.1016/j.ando.2017.04.009
[97] Griffin MD, Pereira SR, DeBari MK, Abbott RD. Mechanisms of action, chemical characteristics, and model systems of obesogens. BMC Biomed Eng. 2020;2(1):6. doi:10.1186/s42490-020-00040-6
[98] Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19(5):557-566. doi:10.1038/nm.3159
[99] Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB, et al. Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation. Environ Health Perspect. 2015;123(7):679-688. doi:10.1289/ehp.1409055
[100] Decherf S, Demeneix BA. The Obesogen Hypothesis: A Shift of Focus from the Periphery to the Hypothalamus. Journal of Toxicology and Environmental Health, Part B. 2011;14(5-7):423-448. doi:10.1080/10937404.2011.578561
[101] Street ME, Bernasconi S. Endocrine-Disrupting Chemicals in Human Fetal Growth. Int J Mol Sci. 2020;21(4):1430. doi:10.3390/ijms21041430
[102] Valvi D, Mendez MA, Martinez D, Grimalt JO, Torrent M, Sunyer J, et al. Prenatal Concentrations of Polychlorinated Biphenyls, DDE, and DDT and Overweight in Children: A Prospective Birth Cohort Study. Environ Health Perspect. 2012;120(3):451-457. doi:10.1289/ehp.1103862
[103] Nicole W. Phthalates and Childhood Body Fat: Study Finds No Evidence of Obesogenicity. Environ Health Perspect. 2016;124(4). doi:10.1289/ehp.124-A78
[104] Braun JM, Lanphear BP, Calafat AM, Deria S, Khoury J, Howe CJ, et al. Early-Life Bisphenol A Exposure and Child Body Mass Index: A Prospective Cohort Study. Environ Health Perspect. 2014;122(11):1239-1245. doi:10.1289/ehp.1408258
[105] Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, et al. Bisphenol A and Adiposity in an Inner-City Birth Cohort. Environ Health Perspect. 2016;124(10):1644-1650. doi:10.1289/EHP205
[106] Valvi D, Casas M, Mendez MA, Ballesteros-Gómez A, Luque N, Rubio S, et al. Prenatal Bisphenol A Urine Concentrations and Early Rapid Growth and Overweight Risk in the Offspring. Epidemiology. 2013;24(6):791-799. doi:10.1097/EDE.0b013e3182a67822
[107] Buckley JP, Herring AH, Wolff MS, Calafat AM, Engel SM. Prenatal exposure to environmental phenols and childhood fat mass in the Mount Sinai Children’s Environmental Health Study. Environ Int. 2016;91:350-356. doi:10.1016/j.envint.2016.03.019
[108] Heppner KM, Kirigiti M, Secher A, Paulsen SJ, Buckingham R, Pyke C, et al. Expression and Distribution of Glucagon-Like Peptide-1 Receptor mRNA, Protein and Binding in the Male Nonhuman Primate ( Macaca mulatta ) Brain. Endocrinology. 2015;156(1):255-267. doi:10.1210/en.2014-1675
[109] Trasande L, Attina TM, Blustein J. Association Between Urinary Bisphenol A Concentration and Obesity Prevalence in Children and Adolescents. JAMA. 2012;308(11):1113. doi:10.1001/2012.jama.11461
[110] Correia-Sá L, Kasper-Sonnenberg M, Schütze A, Pälmke C, Norberto S, Calhau C, et al. Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring. Environmental Science and Pollution Research. 2017;24(35):27502-27514. doi:10.1007/s11356-017-0358-7
[111] Li DK, Miao M, Zhou Z, Wu C, Shi H, Liu X, et al. Urine Bisphenol-A Level in Relation to Obesity and Overweight in School-Age Children. PLoS One. 2013;8(6):e65399. doi:10.1371/journal.pone.0065399
[112] Jacobson MH, Woodward M, Bao W, Liu B, Trasande L. Urinary Bisphenols and Obesity Prevalence Among U.S. Children and Adolescents. J Endocr Soc. 2019;3(9):1715-1726. doi:10.1210/js.2019-00201
[113] Li L, Xu S, Lian Q. The mediating function of obesity on endocrine-disrupting chemicals and insulin resistance in children. Journal of Pediatric Endocrinology and Metabolism. 2022;35(9):1169-1176. doi:10.1515/jpem-2022-0354
[114] Neel BA, Sargis RM. The Paradox of Progress: Environmental Disruption of Metabolism and the Diabetes Epidemic. Diabetes. 2011;60(7):1838-1848. doi:10.2337/db11-0153
[115] Lin Y, Wei J, Li Y, Chen J, Zhou Z, Song L, et al. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat. American Journal of Physiology-Endocrinology and Metabolism. 2011;301(3):E527-E538. doi:10.1152/ajpendo.00233.2011
[116] Perreault L, McCurdy C, Kerege AA, Houck J, Færch K, Bergman BC. Bisphenol A Impairs Hepatic Glucose Sensing in C57BL/6 Male Mice. PLoS One. 2013;8(7):e69991. doi:10.1371/journal.pone.0069991
[117] Song Y, Chou EL, Baecker A, You NCY, Song Y, Sun Q, et al. Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: A systematic review and meta-analysis. J Diabetes. 2016;8(4):516-532. doi:10.1111/1753-0407.12325
[118] Petrakis D, Vassilopoulou L, Mamoulakis C, Psycharakis C, Anifantaki A, Sifakis S, et al. Endocrine Disruptors Leading to Obesity and Related Diseases. Int J Environ Res Public Health. 2017;14(10):1282. doi:10.3390/ijerph14101282
[119] Hauner H, Petruschke Th, Russ M, Röhrig K, Eckel J. Effects of tumour necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologia. 1995;38(7):764-771. doi:10.1007/s001250050350
[120] Paz-Filho G, Mastronardi C, Wong ML, Licinio J. Leptin therapy, insulin sensitivity, and glucose homeostasis. Indian J Endocrinol Metab. 2012;16(9):549. doi:10.4103/2230-8210.105571
[121] Hivert MF, Sullivan LM, Fox CS, Nathan DM, D’Agostino RB, Wilson PWF, et al. Associations of Adiponectin, Resistin, and Tumor Necrosis Factor-α with Insulin Resistance. J Clin Endocrinol Metab. 2008;93(8):3165-3172. doi:10.1210/jc.2008-0425
[122] Olszanecka-Glinianowicz M, Kocełak P, Nylec M, Chudek J, Zahorska-Markiewicz B. Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome. Archives of Medical Science. 2012;2:214-218. doi:10.5114/aoms.2012.28547
[123] Gómez-Banoy N, Guseh JS, Li G, Rubio-Navarro A, Chen T, Poirier B, et al. Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans. Nat Med. 2019;25(11):1739-1747. doi:10.1038/s41591-019-0610-4
[124] Song NJ, Kim S, Jang BH, Chang SH, Yun UJ, Park KM, et al. Small Molecule-Induced Complement Factor D (Adipsin) Promotes Lipid Accumulation and Adipocyte Differentiation. PLoS One. 2016;11(9):e0162228. doi:10.1371/journal.pone.0162228
[125] Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436(7049):356-362. doi:10.1038/nature03711
[126] Haas JT, Biddinger SB. Dissecting the role of insulin resistance in the metabolic syndrome. Curr Opin Lipidol. 2009;20(3):206-210. doi:10.1097/MOL.0b013e32832b2024
[127] Bodin J, Bølling AK, Becher R, Kuper F, Løvik M, Nygaard UC. Transmaternal Bisphenol A Exposure Accelerates Diabetes Type 1 Development in NOD Mice. Toxicological Sciences. 2014;137(2):311-323. doi:10.1093/toxsci/kft242
[128] Bohacek J, Mansuy IM. Epigenetic Inheritance of Disease and Disease Risk. Neuropsychopharmacology. 2013;38(1):220-236. doi:10.1038/npp.2012.110
[129] Bodin J, Stene LC, Nygaard UC. Can Exposure to Environmental Chemicals Increase the Risk of Diabetes Type 1 Development? Biomed Res Int. 2015;2015:1-19. doi:10.1155/2015/208947
[130] Katsikantami I, Sifakis S, Tzatzarakis MN, Vakonaki E, Kalantzi OI, Tsatsakis AM, et al. A global assessment of phthalates burden and related links to health effects. Environ Int. 2016;97:212-236. doi:10.1016/j.envint.2016.09.013
[131] Wang Q, Jin T. The role of insulin signaling in the development of β-cell dysfunction and diabetes. Islets. 2009;1(2):95-101. doi:10.4161/isl.1.2.9263
[132] Timme-Laragy AR, Sant KE, Rousseau ME, diIorio PJ. Deviant development of pancreatic beta cells from embryonic exposure to PCB-126 in zebrafish. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2015;178:25-32. doi:10.1016/j.cbpc.2015.08.012
[133] Hectors TLM, Vanparys C, van der Ven K, Martens GA, Jorens PG, van Gaal LF, et al. Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function. Diabetologia. 2011;54(6):1273-1290. doi:10.1007/s00125-011-2109-5
[134] Lee DH, Steffes MW, Sjödin A, Jones RS, Needham LL, Jacobs DR. Low Dose Organochlorine Pesticides and Polychlorinated Biphenyls Predict Obesity, Dyslipidemia, and Insulin Resistance among People Free of Diabetes. PLoS One. 2011;6(1):e15977. doi:10.1371/journal.pone.0015977
[135] Gray SL, Shaw AC, Gagne AX, Chan HM. Chronic Exposure to PCBs (Aroclor 1254) Exacerbates Obesity-Induced Insulin Resistance and Hyperinsulinemia in Mice. J Toxicol Environ Health A. 2013;76(12):701-715. doi:10.1080/15287394.2013.796503
[136] Howell G, Mangum L. Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells. Toxicology in Vitro. 2011;25(1):394-402. doi:10.1016/j.tiv.2010.10.015
[137] Williams AS, Kang L, Wasserman DH. The extracellular matrix and insulin resistance. Trends in Endocrinology & Metabolism. 2015;26(7):357-366. doi:10.1016/j.tem.2015.05.006
[138] Shao W, Brown M. Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy. Breast Cancer Research. 2003;6(1):39. doi:10.1186/bcr742
[139] Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H. Phosphatidylinositol 3-Kinase/AKT-mediated Activation of Estrogen Receptor α. Journal of Biological Chemistry. 2001;276(13):9817-9824. doi:10.1074/jbc.M010840200
[140] Marchand A, Tomkiewicz C, Marchandeau JP, Boitier E, Barouki R, Garlatti M. 2,3,7,8-Tetrachlorodibenzo- p -dioxin Induces Insulin-Like Growth Factor Binding Protein-1 Gene Expression and Counteracts the Negative Effect of Insulin. Mol Pharmacol. 2005;67(2):444-452. doi:10.1124/mol.104.004010
[141] Zuo Z, Wu T, Lin M, Zhang S, Yan F, Yang Z, et al. Chronic Exposure to Tributyltin Chloride Induces Pancreatic Islet Cell Apoptosis and Disrupts Glucose Homeostasis in Male Mice. Environ Sci Technol. 2014;48(9):5179-5186. doi:10.1021/es404729p
[142] Alonso-Magdalena P, García-Arévalo M, Quesada I, Nadal Á. Bisphenol-A Treatment During Pregnancy in Mice: A New Window of Susceptibility for the Development of Diabetes in Mothers Later in Life. Endocrinology. 2015;156(5):1659-1670. doi:10.1210/en.2014-1952
[143] Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A. The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function In Vivo and Induces Insulin Resistance. Environ Health Perspect. 2006;114(1):106-112. doi:10.1289/ehp.8451
[144] Camacho L, Lewis SM, Vanlandingham MM, Olson GR, Davis KJ, Patton RE, et al. A two-year toxicology study of bisphenol A (BPA) in Sprague-Dawley rats: CLARITY-BPA core study results. Food and Chemical Toxicology. 2019;132:110728. doi:10.1016/j.fct.2019.110728
[145] Predieri B, Iughetti L, Bernasconi S, Street ME. Endocrine Disrupting Chemicals’ Effects in Children: What We Know and What We Need to Learn? Int J Mol Sci. 2022;23(19):11899. doi:10.3390/ijms231911899